Genetics and epigenetics of autism spectrum disorder—current evidence in the field

Abstract

Autism spectrum disorders (ASD) is a heterogenous group of neurodevelopmental disorders characterized by problems in social interaction and communication as well as the presence of repetitive and stereotyped behavior. It is estimated that the prevalence of ASD is 1–2% in the general population with the average male to female ratio 4–5:1. Although the causes of ASD remain largely unknown, the studies have shown that both genetic and environmental factors play an important role in the etiology of these disorders. Array comparative genomic hybridization and whole exome/genome sequencing studies identified common and rare copy number or single nucleotide variants in genes encoding proteins involved in brain development, which play an important role in neuron and synapse formation and function. The genetic etiology is recognized in ~ 25–35% of patients with ASD. In this article, we review the current state of knowledge about the genetic etiology of ASD and also propose a diagnostic algorithm for patients.

http://bit.ly/2CaHAph

Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases

Summary

Many compounds structurally similar to chromones have been developed to enhance the sensitizing effect of cancer cells to chemotherapeutic agents. Most of these compounds have been shown to promote this sensitization by targeting the repair pathways. One such compound is LTUR6, which enhances the sensitization of doxorubicin to colon cancer cells HT29, by inhibiting the phosphorylation of the double stranded break (DSB) repair enzyme AKT. The downstream regulatory targets of AKT that enhance doxorubicin mediated cytotoxicity in the presence of LTUR6 remains elusive. In this study, we performed comparative analyses of 43 kinase phosphorylation sites using the human phospho-kinase array proteome profiler. Results revealed altered expression levels of multiple proteins that regulated apoptotic signalling pathways. Increased activation of mTOR, RSK1/2/3, p38α and PRAS40 after combination treatment with LTUR6 and doxorubicin over doxorubicin alone was observed. This study provides a deeper insight into the key proteins involved and presents a novel molecular pathway.

http://bit.ly/2Cdiy9e

Influence of Preoperative Weight Loss on Outcomes of Bariatric Surgery for Patients Under the Enhanced Recovery After Surgery Protocol

Abstract

Introduction

The enhanced recovery after surgery (ERAS) protocol, which emphasizes preoperative interventions, is safely implemented in patients undergoing bariatric surgery. Patients are additionally encouraged to achieve weight loss preoperatively. We aimed to identify factors contributing to preoperative weight loss and assess their influence on outcomes of bariatric surgery among patients under the ERAS protocol.

Materials and Methods

We reviewed a prospectively created database in two bariatric centers with 909 bariatric patients treated in accordance with ERAS principles. The database included demographic characteristics, factors related to the surgery or perioperative period, and short-term outcomes. Our endpoints included analyses of (1) factors potentially contributing to preoperative weight loss and (2) the influence of preoperative weight loss on short-term outcomes of bariatric treatment.

Results

Diabetes mellitus (p = 0.007), obstructive sleep apnea (p < 0.001), and previous surgery (p = 0.012) were identified as predictors of preoperative weight loss. Steatohepatitis (p < 0.001) and respiratory disorder (p = 0.004) decreased the chance of achieving satisfactory preoperative body mass reduction. Except for operative time, early outcomes of bariatric surgery were not influenced by preoperative weight loss. Patients who achieved preoperative weight loss were less likely to be lost to follow-up (p = 0.023). Postoperative weight loss was better in patients who could lose ≥ 5% total weight preoperatively (p = 0.009).

Conclusion

Unsatisfactory preoperative weight loss among patients treated under ERAS principles is not associated with increased risk of complications. Satisfactory preoperative weight loss predicts superior postoperative weight loss and follow-up participation.

http://bit.ly/2H5ySyi

Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases

Summary

Many compounds structurally similar to chromones have been developed to enhance the sensitizing effect of cancer cells to chemotherapeutic agents. Most of these compounds have been shown to promote this sensitization by targeting the repair pathways. One such compound is LTUR6, which enhances the sensitization of doxorubicin to colon cancer cells HT29, by inhibiting the phosphorylation of the double stranded break (DSB) repair enzyme AKT. The downstream regulatory targets of AKT that enhance doxorubicin mediated cytotoxicity in the presence of LTUR6 remains elusive. In this study, we performed comparative analyses of 43 kinase phosphorylation sites using the human phospho-kinase array proteome profiler. Results revealed altered expression levels of multiple proteins that regulated apoptotic signalling pathways. Increased activation of mTOR, RSK1/2/3, p38α and PRAS40 after combination treatment with LTUR6 and doxorubicin over doxorubicin alone was observed. This study provides a deeper insight into the key proteins involved and presents a novel molecular pathway.

http://bit.ly/2Cdiy9e

Comment on: Pharmacokinetics, Pharmacodynamics, and Safety of the Novel Calcimimetic Agent Evocalcet in Healthy Japanese Subjects: First-in-Human Phase I Study

http://bit.ly/2FrwL5N

Response to Comments on “Pharmacokinetics, Pharmacodynamics, and Safety of the Novel Calcimimetic Agent Evocalcet in Healthy Japanese Subjects: First-in-Human Phase I Study”

http://bit.ly/2FjYINg

Association between inflammatory back pain features, acute and structural sacroiliitis on MRI, and the diagnosis of spondyloarthritis

Abstract

Objectives

To evaluate the association between inflammatory back pain (IBP) features, acute and structural MRI findings suggestive of sacroiliitis, and diagnosis of spondyloarthritis (SpA).

Methods

Data from 224 patients who underwent MRI for suspected sacroiliitis (2005–2015) was retrospectively reviewed by an expert rheumatologist for the presence of IBP features and for clinical standard of reference diagnosis. A telephone questionnaire was performed in cases of missing data. Acute and structural MRI parameters were scored by an experienced radiologist for the presence of sacroiliitis using the Assessment of Spondyloarthritis International Society (ASAS) criteria, Berlin score, and observer's global impression (GI) scores. Association between IBP features and MRI scores, and odds ratio for SpA diagnosis, were calculated.

Results

One hundred ninety-three subjects were included (119 F:74 M, mean age 39.7 ± 15.6, mean follow-up 49 ± 18 months). Fifty-two (26.9%) subjects were diagnosed with SpA. IBP scores were significantly higher in SpA patients (p < 0.001). IBP, ASAS, and GI MRI scores were significantly associated with the SpA diagnosis (p < 0.001 for all). The presence of night pain and morning stiffness was significantly associated with sacroiliac-joints' bone marrow edema (BME, p < 0.05). Sensitivity for diagnosis of SpA was high for IBP (96%) and low for the MRI parameters (26.9–57.4%), and specificity was low for IBP (32%) and high for the MRI parameters (88.3–94.3%).

Conclusions

The presence of IBP features is highly associated with diagnosis of SpA and correlates with MRI BME, all probably reflect inflammation. The combination of IBP and MRI should be the cornerstone in the clinician's final diagnosis of SpA.

http://bit.ly/2Fm2UeN

A Bayesian mixed treatment comparison of efficacy of biologics and small molecules in early rheumatoid arthritis

Abstract

The current paradigm in the management of rheumatoid arthritis (RA) is to treat patients in the early stage of the disease (ERA). Previous meta-analysis-based mixed treatment comparisons (MTCs), aimed to identify the most effective drugs in ERA, are biased by the wide "window" of early definition, ranging from 6 months to 2 years. The aim of this study was to estimate through a Bayesian Network Meta-Analysis which biologics or small molecules are more likely to achieve a 1-year good clinical response in ERA patients with disease duration < 1 year. According to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, randomized controlled trials (RCTs) of biologic agents and small molecules in combination with MTX to treat patients affected with ERA lasting < 1 year were searched through MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov between 1990 and September 2017. The outcome of interest was the achievement of American College of Rheumatology (ACR) 50 and ACR 70 response at 1 year. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses, using a fixed effect model. Fourteen studies were included in the analysis. Tofacitinib (64.83%) followed by Etanercept (23.26%) were the drugs with the highest probability of achieving ACR50 response. Rituximab showed the highest probability of inducing ACR70 response (52.81%) followed by Etanercept (26.85%). This is the first MTC involving only RCTs on ERA patients with disease duration < 1 year. Tofacitinib and rituximab were the drugs ranked first in inducing 1-year ACR50 and ACR70 response, respectively.

http://bit.ly/2Fkqyt0

The complexity of an overlap type resistant cryoglobulinemia: a case report and review of the literature

Abstract

Type I cryoglobulinemia is associated with B cell proliferative diseases, whereas essential mixed cryoglobulinemia is classically associated with infections, malignancy, and autoimmune diseases, but may be idiopathic. Prognosis in patients with grave manifestations and renal involvement is often poor. We report a case of a 40-year-old woman, 2 weeks post-partum for pre-eclampsia who was hospitalized with nephritic syndrome and acute renal failure. The patient harbored type I and type II cryoglobulinemia. Renal and cutaneous biopsies confirmed the diagnosis; however, an underlying etiology was not established. A bone marrow biopsy suggested monoclonal gammopathy of undetermined source (MGUS). Despite therapy with intravenous cyclophosphamide, rituximab, plasmapheresis, dialysis, and bortezomib, the patient succumbed after 8 months of hospitalization. We suggest that an overlap entity of types I and II cryoglobulinemia with severe multi-organ involvement not only is rare but also may be resistant to conventional therapy and fatal.

http://bit.ly/2FkOeg6

Lifetime extension of humpback whale skin fibroblasts and their response to lipopolysaccharide (LPS) and a mixture of polychlorinated biphenyls (Aroclor)

Abstract

Marine mammals, such as whales, have a high proportion of body fat and so are susceptible to the accumulation, and associated detrimental health effects, of lipophilic environmental contaminants. Recently, we developed a wild-type cell line from humpback whale fibroblasts (HuWa). Extensive molecular assessments with mammalian wild-type cells are typically constrained by a finite life span, with cells eventually becoming senescent. Thus, the present work explored the possibility of preventing senescence in the HuWa cell line by transfection with plasmids encoding the simian virus large T antigen (SV40T) or telomerase reverse transcriptase (TERT). No stable expression was achieved upon SV40 transfection. Transfection with TERT, on the other hand, activated the expression of telomerase in HuWa cells. At the time of manuscript preparation, the transfected HuWa cells (HuWa_TERT) have been stable for at least 59 passages post-transfection. HuWa_TERT proliferate rapidly and maintain initial cell characteristics, such as morphology and chromosomal stability. The response of HuWa_TERT cells to an immune stimulant (lipopolysaccharide (LPS)) and an immunotoxicant (Aroclor1254) was assessed by measurement of intracellular levels of the pro-inflammatory cytokines interleukin (IL)-6, IL-1β and tumour necrosis factor (TNF)-α. HuWa_TERT cells constitutively express IL-6, IL-1β and TNFα. Exposure to neither LPS nor Aroclor1254 had an effect on the levels of these cytokines. Overall, this work supports the diverse applicability of HuWa cell lines in that they display reliable long-term preservation, susceptibility to exogenous gene transfer and enable the study of humpback whale-specific cellular response mechanisms.

http://bit.ly/2TCtt3h

KUNO-Kids birth cohort study: rationale, design, and cohort description

Abstract

Background

Birth cohort studies can contribute substantially to the understanding of health and disease — in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.

Results

After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.

Conclusions

The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.

http://bit.ly/2RAwCmX

Early child development: a challenge in China

http://bit.ly/2SMNHHo

Monoaminergic system and depression

Abstract

Major depressive disorder is a severe, disabling disorder that affects around 4.7% of the population worldwide. Based on the monoaminergic hypothesis of depression, monoamine reuptake inhibitors have been developed as antidepressants and nowadays, they are used widely in clinical practice. However, these drugs have a limited efficacy and a slow onset of therapeutic action. Several strategies have been implemented to overcome these limitations, including switching to other drugs or introducing combined or augmentation therapies. In clinical practice, the most often used augmenting drugs are lithium, triiodothyronine, atypical antipsychotics, buspirone, and pindolol, although some others are in the pipeline. Moreover, multitarget antidepressants have been developed to improve efficacy. Despite the enormous effort exerted to improve these monoaminergic drugs, they still fail to produce a rapid and sustained antidepressant response in a substantial proportion of depressed patients. Recently, new compounds that target other neurotransmission system, such as the glutamatergic system, have become the focus of research into fast-acting antidepressant agents. These promising alternatives could represent a new pharmacological trend in the management of depression.

http://bit.ly/2CaVJDa

Regulation of the phosphate metabolism in Streptomyces genus: impact on the secondary metabolites

Abstract

The analysis of the inorganic phosphate effect over the antibiotics production is a long-distance history in the Streptomyces genus, which began almost at the same time that Michael Ende published his book entitled The Neverending Story. In some way, the unveiling of the pho regulon and its influence over the secondary metabolites production is an unfinished story, which keeps this subject as a trending topic, nowadays. Up to date, different studies have been releasing knowledge about particular areas of the pho regulon of different Streptomyces species. Nevertheless, for the first time, these knowledge drops are grouped in a review presenting a broad overview of the phosphate regulation and its impact over the secondary metabolites production in industrially relevant species. Even though the genetic response against phosphate scarcity is similar, as a whole, in different Streptomyces species, the fine-tuning is species-specific. Thus, the response regulator PhoP directly controls the secondary metabolites production in some species, whereas it regulates them in an indirect manner in other species. This information, unraveled in this review, is the result of the intensive analysis along last decade in several species of the genus that is allowing to distinguish how the phosphate response is unleashed in Streptomyces coelicolor, Streptomyces lividans, Streptomyces natalensis, Streptomyces lydicus, Streptomyces avermitilis, and Streptomyces tsukubaensis.

http://bit.ly/2HhmImn

Effect of ultrasonication and thermal and pressure treatments, individually and combined, on inactivation of Bacillus cereus spores

Abstract

Bacillus cereus spores are a concern to the food industry due to their high resistance to processing and their ability to germinate to vegetative cells under suitable conditions. This research aimed to elucidate the mechanisms of Bacillus cereus spore inactivation under ultrasonication (US) combined with thermal (thermosonication, TS) treatments, with pressure (manosonication, MS) treatments, and with thermal and pressure (manothermosonication, MTS) treatments. Electronic microscopy, dipicolinic acid (DPA) release, and flow cytometric assessments were used to investigate the inactivation effect and understand the inactivation mechanisms. The sporicidal effects of the US and thermal treatment were slight, and the MS and TS also showed little inactivation effect. However, ultrasonication promoted the detachment of the exosporium, thereby reducing the spore's ability to adhere to a surface, while the thermal treatment induced a decrease in the electron density in the nucleoid of bacterium, which retained a relatively intact exosporium and coat. MS caused 92.54% DPA release, which might be due to triggering of the germinant receptors or releasing of ions and Ca²⁺-DPA. In addition, the morphological changes such as core hydration and cortex degradation were significant after treatment with MS. The release of DPA and the morphological changes were responsible for the reduction in thermal resistance. The MTS showed a remarkable inactivation effect of 3.12 log CFU/mL reductions after 30 min of treatment. It was the most effective treatment and exhibited a large fraction of damage. In addition, the MTS had a significant impact on the intracellular structure of the spores, with the coat destroyed and the cortex damaged. These results indicated that ultrasonication combined with thermal and pressure treatments had a significant sporicidal effect on Bacillus cereus spores and could be a promising green sterilization technology.

http://bit.ly/2RiomIF

Synthesis of water-soluble conjugated polymer, poly(N-3-sulfopropylaniline) and the study of its glucose sensing property

Abstract

A water-soluble conjugated polymer, poly(N-3-sulfopropylaniline) (PSPA) with 7–10 controlled repeating units has been synthesized through oxidative polymerization of sulfopropylaniline (SPA) monomer, which is prepared by N-alkylation of aniline using 3-propane sultone. The glass transition temperature (T_g), thermal stability, molecular weight and size distribution of the synthesized polymer were investigated by DSC, TGA and MALDI TOFF respectively. The spectral (UV-Vis, PL, NMR, FTIR) analysis has been done to develop a facile colorimetric method to sense glucose (a biomarker of diabetes). The synthesized polymers could detect glucose up to nanomolar (10⁻⁹ M), which are 10⁶ fold less than the level of a diabetic patient (4 × 10⁻³-9 × 10⁻³ M). It is also observed that the naked eye can sense up to decimolar (10⁻¹ M) level. The polymerization process and the chemistry of colorimetric sensing are explained through spectral and cyclic voltammetry analysis. The polymerization and the sensing of glucose occurred through the electron transfer dependent color change processes.

Graphical abstract

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http://bit.ly/2Fj9zY8

The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage

Abstract

Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was administered prophylactically by intraperitoneal injection. SAH grade, neurological score, brain water content, and BBB permeability were measured at 24 h after SAH induction. In addition, cortical samples taken at 24 h after SAH were analyzed to explore oxidative stress, microvascular mural cell apoptosis, microspasm, and microthrombosis. Edaravone treatment significantly ameliorated neurological deficits, brain edema, and BBB disruption. In addition, oxidative stress-induced modifications and subsequent apoptosis of microvascular endothelial cells and pericytes increased after SAH induction, while the administration of edaravone suppressed this. Consistent with apoptotic cell inhibition, microthromboses were also inhibited by edaravone administration. Oxidative stress plays a pivotal role in the induction of multiple pathological changes in microvessels in EBI. Antioxidants are potential candidates for the treatment of microvascular disturbances after SAH.

http://bit.ly/2CdNyWv

Variation in phenotypic resistance to gastrointestinal nematodes in hair sheep in the humid tropics of Mexico

Abstract

The objective of the study was to evaluate phenotypic resistance against gastrointestinal nematodes in Blackbelly, Pelibuey and Katahdin ewes before pregnancy in the humid tropics of Mexico. Individual faecal and blood samples were taken in 59 Pelibuey, 69 Blackbelly and 73 Katahdin ewes. The egg count per gram of faeces (EPG) of gastrointestinal nematodes (GINs) was determined. The percentage of packed cell volume (PCV) and body condition score (BCS) of each animal were also recorded. The ewes were segregated as susceptible, intermediate or resistant based on the EPG using the quartile method. The data were analysed using the general linear method, and the means between breeds were compared by Tukey's test. The relationships between the EPG, PCV and BCS were evaluated by Spearman correlation. The Katahdin ewes showed the highest EPG counts (3613.6 ± 5649) compared to the Blackbelly and Pelibuey ewes (576.1 ± 1009 and 56.8 ± 187, respectively, P < 0.01). The PCV values between breeds were similar (P > 0.05). The susceptible ewes had the highest EPG counts and the lowest PCV percentage (5069 ± 6404 and 22.8% ± 8.1% respectively) compared to the resistant ewes (P < 0.01). A higher percentage of Katahdin ewes were susceptible compared to the other breeds (P < 0.05). The main GIN species were Haemonchus contortus, Trichostrongylus colubriformis and Cooperia curticei. In conclusion, Katahdin ewes showed susceptibility to GIN compared to Blackbelly and Pelibuey ewes before the pregnancy period in the humid tropics of Mexico.

http://bit.ly/2ADsI2G

A case of foreign accent syndrome in a patient affected by a complex functional movement disorder

http://bit.ly/2CcMPoE

Reading without spaces: The role of precise letter order

Abstract

Prior research points to efficient identification of embedded words as a key factor in facilitating the reading of text printed without spacing between words. Here we further tested the primary role of bottom-up word identification by altering this process with a letter transposition manipulation. In two experiments, we examined silent reading and reading aloud of normal sentences and sentences containing words with letter transpositions, in both normally spaced and unspaced conditions. We predicted that letter transpositions should be particularly harmful for reading unspaced text. In line with our prediction, the majority of our measures of reading fluency showed that unspaced text with letter transpositions was disproportionately difficult to read. These findings provide further support for the claim that reading text without between-word spacing relies principally on efficient bottom-up processing, enabling accurate word identification in the absence of visual cues to identify word boundaries.

http://bit.ly/2RhXSqU

Different effects of glucocorticoids on darunavir plasma concentrations

http://bit.ly/2QyXRtp

Monocular channels have a functional role in phasic alertness and temporal expectancy

Abstract

The literature has long emphasized the neocortex's role in the tangled phasic-alertness and temporal-expectancy processes. In this work, we examined whether subcortical, monocular mechanisms have a functional role in these processes. This was done by assessing phasic alertness and temporal expectancy independently using a cue–target eye-of-origin manipulation. Participants performed target detection tasks in which a central cue and its ensuing peripheral target were each presented either to the same eye or to a different eye. In Experiment 1, phasic alertness, independent of temporal expectancy, was manipulated by presenting an alerting cue prior to the target presentation. The alerting effect elicited by the cue lasted for a longer duration when the cue and target were presented to the same eye than when they were presented to different eyes, indicating the involvement of subcortical regions in phasic alertness. In Experiment 2, the cue's temporal predictability regarding the target's onset time was manipulated by changing the cue–target interval's foreperiod distribution. A modulation in temporal expectancy was found when both the cue and the target were presented to the same eye, demonstrating the importance of subcortical mechanisms in temporal expectancy. Together, the results demonstrate that monocular channels are functionally involved in both phasic alertness and temporal expectancy. This study suggests that both phasic alertness and temporal expectancy are functionally dependent on monocular channels of the visual stream, and highlights the importance of direct examination of primitive, subcortical regions in higher cognitive functioning (e.g., temporal expectancy).

http://bit.ly/2RArY8s

The uphill battle for action-specific perception

Abstract

The action-specific account of perception states that a perceiver's ability to act influences the perception of the environment. For example, participants tend to perceive distances as farther when presented up hills than on the flat ground. This tendency is known as the distance-on-hill effect. However, there is debate as to whether these types of effects are truly perceptual. Critics of the action-specific account of perception claim that the effects could be due to participants guessing the hypothesis and trying to comply with the experimental demands. The present study aims to explore the distance-on-hill effect and determine whether it is truly perceptual or whether past results were due to response bias. Participants judged the relative distance to targets on a hill and the flat ground. We found the distance-on-hill effect in virtual reality using a visual matching task. The distance-on-hill effect persisted even when participants were given explicit feedback about their estimates. We also found that the effect went away, as predicted by a perceptual explanation, when participants had to match the distance between two cones that were both on hills. These results offer important steps toward the painstaking task of determining whether action's effect on perception is truly perceptual.

http://bit.ly/2H7jaCT

Separating after-effects of target and distractor processing in the tactile sensory modality

Abstract

The present study investigated the cognitive mechanisms underlying aftereffects of tactile target and distractor processing. In our experiment, participants selected tactile target stimuli against simultaneously presented tactile distractor stimuli in prime–probe sequences. Tactile distractors in each prime/probe trial were either response incompatible (i.e., interfering at the response level) or response neutral (i.e., noninterfering at the response level), manipulated between participants. Furthermore, distractor relation (repetition vs. change) and response relation (repetition vs. change) across prime–probe sequences were orthogonally varied within participants. Thus, independent estimates of distractor repetition main effects (that are attributable to distractor-specific prime processing and have previously been interpreted in terms of inhibition or episodic retrieval processes) and the modulation of distractor repetition effects due to response relation (that is target specific and can only be explained in terms of event-file retrieval) were assessed (see Giesen, Frings, & Rothermund, Memory & Cognition, 40, 373–387, 2012). Replicating previous studies with visual stimuli, simple distractor repetition effects were stronger for response-incompatible compared with response-neutral tactile distractors. In contrast, event-file retrieval as reflected in distractor-response binding retrieval effects was not modulated by whether the distractors were response incompatible or response neutral. Together, these findings highlight that in tactile tasks, prime-distractor and prime-target processing both hold the potential to cause aftereffects during probe performance.

http://bit.ly/2RCC20G

Magnetic resonance-guided laser interstitial thermal therapy for the treatment of non-lesional insular epilepsy in pediatric patients: thermal dynamic and volumetric factors influencing seizure outcomes

Abstract

Purpose

To investigate the safety and efficacy of stereoelectroencephalography (sEEG) directed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) in medically refractory insular epilepsy in pediatric patients, define the relationship between ablation volumes and seizure control, and analyze the relationship between thermal energy and ablation volumes.

Methods

A single-institution, retrospective review of pediatric patients with insular epilepsy who underwent sEEG directed MRgLITT over a 10-month period was performed. Perioperative, imaging, and outcome data were analyzed. Seizure outcomes were determined based on Engel score (Engel I versus Engel II–IV). Insula and ablation volumes were measured, and the proportion of insula volume ablated was calculated. Thermal energy was calculated in joules.

Results

Four patients underwent sEEG directed MRgLITT of insular epileptogenic foci. The ablation volume was higher in patients with Engel I outcome (3.93 cm³) compared to Engel II–IV outcome (1.02 cm³). The proportion of ablation to insula volume was lowest in patients with Engel II–IV outcome (25.09%). The mean energy requirement to create a unit volume of ablation in the insula is 1205.86 J. A linear trend was noted between thermal ablation energy and ablation volume (R² = 0.884). Over a mean follow-up period of 104 days, three patients were seizure-free (Engel I), and one patient saw significant improvement in seizure frequency (Engel III).

Conclusions

The proportion of insula ablated, as well as the volume of ablation, are related to seizure outcome with increasing ablation volumes corresponding to improved seizure control. Further analysis of insula laser ablation thermal dynamics and volumes is needed.

http://bit.ly/2TEr7AV

Microarray expression profile of circular RNAs and mRNAs in children with systemic lupus erythematosus

Abstract

Background

Recently, it was reported that circular RNAs (circRNAs) play the crucial role in many physiological and biological processes and can be used as biomarkers. However, the information about circRNAs in children with systemic lupus erythematosus (SLE) is limited. The aim of this study is to determine the expression of circRNAs in children with SLE and investigate the significance of circRNA for diagnosing SLE.

Methods

Microarray profile of circRNAs and mRNAs was performed for identifying the changes in expression of circRNAs and mRNAs between children with SLE and healthy children. Quantitative polymerase chain reaction (qPCR) was used to confirm the results. Spearman correlation test was performed to assess the correlation between circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value.

Results

A comparison between the children with SLE and healthy children revealed that 348 circRNAs and 1162 mRNAs were expressed differentially. The authors constructed a complex circRNA target network consisting of 307 matched circRNA-mRNA pairs for 124 differentially expressed circRNAs (74 circRNAs were upregulated, and 50 circRNAs were downregulated) and 142 differentially expressed mRNAs (83 mRNAs were upregulated, and 59 mRNAs were downregulated) by using gene co-expression network analysis. The competing for endogenous RNA (ceRNA) network includes 42 differentially expressed circRNAs, 41 differentially expressed mRNAs, and 71 predicted miRNAs. Among these SLE patients, we detected that the hsa_circ_0021372 and hsa_circ_0075699 levels are associated with C3 and C4 levels in children with SLE. The hsa_circ_0057762 level is positively associated with the SLEDAI-2K score. The ROC curves of circRNAs showed that the levels of hsa_circ_0057762 (AUC 0.804, 95% CI 0.607–1.0, P = 0.02) and hsa_circ_0003090 (AUC 0.848, 95% CI 0.688–1.0, P = 0.008) could differentiate the patients with SLE from the healthy controls.

Conclusions

We firstly characterized the expression profiles of circRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insight into the mechanisms of SLE pathogenesis, and circRNAs may serve as useful biomarkers for SLE.

http://bit.ly/2ACuKjY

Automated Gait Analysis Detects Improvements after Intracellular σ Peptide Administration in a Rat Hemisection Model of Spinal Cord Injury

Abstract

A promising treatment strategy for spinal cord injury (SCI) is to reduce inhibition from chondroitin sulfate proteoglycans (CSPGs). For example, administering intracellular σ peptide (ISP) can improve the ability of axons to cross inhibitory CSPGs and improve function in rodent models of SCI. To translate such treatments into the clinic, we need robust and sensitive methods for studying rodent models. In this study, we applied a newly developed suite of quantitative gait analysis tools: gait analysis instrumentation and technology optimized for rodents (GAITOR), which consists of an arena and open-source software (AGATHA: automated gait analysis through hues and areas). We showed that GAITOR can be used to detect subtle functional improvements (measured by hindlimb duty factor imbalance) in rats following ISP administration in a T10 hemisection injury model. We demonstrated that SCI-specific parameters (right paw placement accuracy and phase dispersion) can be easily added to GAITOR to track recovery. We confirmed the gait observations via retrograde tracer uptake. We concluded that GAITOR is a powerful tool for measuring recovery after moderate/mild SCI, and could be used to replace expensive/inflexible commercially-available gait analysis techniques.

http://bit.ly/2FejMVu

Technical Feasibility and Design of a Shape Memory Alloy Support Device to Increase Ejection Fraction in Patients with Heart Failure

Abstract

Purpose

Heart failure is increasingly prevalent in the elderly. Treatment of patients with heart failure aims at improving their clinical condition, quality of life, prevent hospital (re)admissions and reduce mortality. Unfortunately, only a select group of heart failure patients with reduced ejection fraction are eligible for Cardiac Resynchronization Therapy where 30–40% remain non-responders and need left ventricular support. The aim of this study is to investigate if a shape memory alloy (SMA) is able to increase the ejection fraction of a mono-chamber static heart model by 5%.

Methods

A pediatric ventilation balloon was used as a heart model (mono-chamber). Flexinol^®, a SMA, was placed around the heart model in multiple configurations and activated using pulse width modulation techniques to determine influence of diameter and configuration on volume displacement. Furthermore, pressure within the heart model was measured with a custom-made pressure sensor.

Results

SMA with a diameter of 0.38 mm, placed in a spiral shape and activated with a duty cycle of 80% and a frequency of 50/min gave the highest ejection fraction increase of 3.5%.

Conclusions

This study demonstrated the feasibility of volume displacement in a static heart model by activation of SMA-wires. Configuration, duty cycle, frequency, pulse intervals and diameter were identified as important factors affecting the activation of SMA-wires on volume displacement. Future research should include the use of parallel SMA-wires, prototype testing in dynamic or ex vivo bench models.

http://bit.ly/2Ffa19P

Prostaglandin A1 Inhibits the Cognitive Decline of APP/PS1 Transgenic Mice via PPARγ/ABCA1-dependent Cholesterol Efflux Mechanisms

Abstract

Prostaglandins (PGs) are early and key contributors to chronic neurodegenerative diseases. As one important member of classical PGs, PGA1 has been reported to exert potential neuroprotective effects. However, the mechanisms remain unknown. To this end, we are prompted to investigate whether PGA1 is a useful neurological treatment for Alzheimer's disease (AD) or not. Using high-throughput sequencing, we found that PGA1 potentially regulates cholesterol metabolism and lipid transport. Interestingly, we further found that short-term administration of PGA1 decreased the levels of the monomeric and oligomeric β-amyloid protein (oAβ) in a cholesterol-dependent manner. In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. Through PPARγ/ABCA1/cholesterol-dependent pathway, PGA1 decreased the expression of presenilin enhancer protein 2 (PEN-2), which is responsible for the production of Aβ. More importantly, long-term administration of PGA1 remarkably decreased the formation of Aβ monomers, oligomers, and fibrils. The actions of PGA1 on the production and deposition of Aβ ultimately improved the cognitive decline of the amyloid precursor protein/presenilin1 (APP/PS1) transgenic mice.

http://bit.ly/2TyQjsC

Histopathological Characteristics of the Orbicularis Oculi Muscle After Lower Blepharoplasty With or Without Myotomy

Abstract

Lower blepharoplasty is a challenging aesthetic procedure. Despite advances in clinical and neuroanatomical studies related to orbicularis oculi muscle innervation, no study has examined its histopathological aspects in different lower blepharoplasty procedures. This study aimed to assess changes in the pretarsal muscle complex in patients treated with transcutaneous lower blepharoplasty with orbicularis myotomy versus those treated with transconjunctival blepharoplasty without myotomy.

Methods

A total of 268 patients underwent blepharoplasty performed by a single surgeon: transcutaneous lower blepharoplasty in 112 (41.7%) and transconjunctival lower blepharoplasty with retroseptal access in 156 (58.2%). Subsequent minor blepharoplasty procedures were performed in 32 patients with lower pretarsal orbicularis oculi muscle biopsy. Connective tissue, fibrillar elastic system, nerves, blood vessels, fiber diameter, and sarcomeres were analyzed.

Results

Without myotomy: collagen, 9.46 ± 0.41%; elastin, 7.03 ± 0.62%; blood vessels, 4.25 ± 0.06%; nerves, 5.2 ± 0.55%; fiber diameter, 62 ± 8.0 μm; and sarcomere, 1.9 ± 0.11 μm. With myotomy: collagen, 19.02 ± 1.66%; elastin, 7.88 ± 1.10%; blood vessels, 5.13 ± 0.70%; nerves, 2.9 ± 0.48%; fiber diameter, 49 ± 6.5 μm; and sarcomere, 1.8 ± 0.17 μm.

Discussion

Excess endomysial connective tissue, particularly between muscle fibers, should be considered pathological. The pathological changes in the pretarsal muscle complex after blepharoplasty with myotomy may have resulted from innervation interruptions as well as vascularization blockages.

Conclusions

Surgeries with myotomy caused significant changes in collagen, nerves, and muscle fiber diameter. These observations strongly suggest the superiority of a technique that preserves orbicularis oculi muscle integrity.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

http://bit.ly/2VEZlWN

Pseudoesotropia in Chinese Children: A Triphasic Development of the Interepicanthal Folds Distance-to-Interpupillary Distance Ratio and Its Changing Perception

Abstract

Purpose

To delineate the development of the interepicanthal fold distance (IEFD) to interpupillary distance (IPD) in Chinese children, and to quantify how their ratio (EFDPD ratio) affects parent's judgment on whether a child's two eyes appear misaligned.

Methods

The values of IPD and IEFD were measured in 750 children, aged between 3 and 17 years. The developmental trend of EFDPD ratio was established. Two hundred parents were shown a series of pictures of children with varying EFDPD ratios and asked to judge whether the child in each picture demonstrated misaligned eyes. Based on the parent's responses, psychometric functional associations with EFDPD ratios were established.

Results

The EFDPD ratios were significantly higher (0.63 ± 0.027) and showed little change among children from 3 to 6 years of age (p = 0.704). During the age of seven to 12 years, however, the EFDPD ratio significantly decreased (p < 0.001) before stabilizing at 0.59 ± 0.023 by the ages of 13 to 17 years (p = 0.376). Children with EFDPD ratios > 0.65 were more likely to be perceived as strabismic by the parents, while children with an EFDPD ratio < 0.55 were rarely perceived as so. As many as 30% of the children aged between 3 and 6 years demonstrated EFDPD ratios > 0.65, and this number reduced to 5% by the age of 12 years.

Conclusions

The development of the EFDPD ratio in Chinese children shows a triphasic pattern, with a large value before the age of 6 years, a quick drop between 7 and 12 years, and little change after 13 years of age. As the EFDPD ratio declines, fewer children appear as strabismic.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

http://bit.ly/2RH4zSS

Managing Pathologic Scars by Injecting Auto-Cross-linked Hyaluronic Acid: A Preliminary Prospective Clinical Study

Abstract

Background

Pathological scars are unattractive and may significantly impair the patient's quality of life. Current treatments provide inconsistent results, and none may be regarded as definitive. Recently, an auto-cross-linked hyaluronic acid (HA) formulation, IAL-SYSTEM ACP, featuring a long residence time and an enhanced safety profile, has been successfully used to prevent surgical adhesions, treat tendon lesions and rejuvenate the face and the décolletage. This study aims to preliminarily investigate whether IAL-SYSTEM ACP may also be effective in treating pathological scars resulting from burns, trauma or iatrogenic causes.

Methods

Patients presenting one pathological scar were prospectively recruited and treated with two IAL-SYSTEM ACP injections carried out two weeks apart. Scar improvement was measured comparing the patient and observer scar assessment scale (POSAS) scores collected before treatment (T0) and 90 days after the second injection (T90) using nonparametric tests. The effect of age and scar type over score variation was investigated through quantile regression analysis.

Results

Forty-one patients, 10 women and 31 men (median age, 34 years) were recruited. No patient dropped out, and no significant adverse event was observed. At T90, the median observer total score decreased by 11 units (− 77.5%) and the median patient total score decreased by 15 units (− 73.7%). The difference was significant (p < 0.001) in both cases. Traumatic injuries and young patient's age were the most significant predictors of a positive treatment outcome.

Conclusions

Treatment of pathological scars by two IAL-SYSTEM ACP injections, carried out two weeks apart, may provide significant clinical benefits. These findings should be the subject of further investigations.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

http://bit.ly/2QzXzCw

Intravenous Corticosteroids as an Adjunctive Treatment for Refractory and Super-Refractory Status Epilepticus: An Observational Cohort Study

Abstract

Introduction

Status epilepticus (SE) represents a neurological emergency that leads to considerable morbidity and mortality. Following failure of first-line therapy, usually with benzodiazepines, there is no clear evidence to guide treatment of refractory SE, although a wide variety of approaches has been described anecdotally.

Objective

The aim of this study was to assess the clinical response to corticosteroids in adults with refractory and super-refractory SE, describing, to the best of our knowledge, the first adult SE cohort treated with corticosteroids.

Methods

We retrospectively analysed our adult SE registry (2006–2017), identifying 15 out of 987 episodes (1.5%) in which corticosteroids were prescribed de novo as adjuvant therapy to a variety of antiepileptic drug regimens. We analysed incident episodes and defined clinical response as SE ceasing within 1 week of administration, without any other medical intervention.

Results

Out of 987 SE episodes, 15 (1.5%) were treated with de novo corticosteroids, corresponding to 12 patients, with increasing prevalence as the SE became refractory (10/411; 2.4% of episodes) and super-refractory (5/108; 4.6% of episodes). One patient (a woman with Rasmussen encephalitis) presented with four SE episodes over a period of 3 years, so only her index SE episode was included in subsequent analyses. The episodes treated were predominantly of inflammatory origin (6/12), such as autoimmune or Rasmussen encephalitis. In five out of 12 (42%) of the considered incident episodes, SE resolved following corticosteroids (all within 3 days). The outcome was better in this responders group (for 2/5 episodes, patients did not have a new handicap at discharge, versus 0/7 in non-responders). In patients with inflammatory and acute symptomatic causes, global prognosis was better than in those with progressive or neurodegenerative aetiologies (6/8 vs. 4/4 had a new handicap at discharge or died).

Conclusions

Our observations seem to support the use of corticosteroids, especially for acute SE of putative inflammatory origin; these compounds, however, were prescribed infrequently.

http://bit.ly/2RhtJIg

Phytomedicines in the Treatment of Migraine

Abstract

Migraine is a disabling neurovascular disorder with few targeted, tolerable and effective treatments. Phytomedicines, or plant-based medicinal formulations, hold great promise in the identification of novel therapeutic targets in migraine. Many patients also turn toward herbal and plant-based therapies for the treatment of their migraines as clinical and preclinical evidence of efficacy increases. Patients seek effective and tolerable treatments instead of or in addition to current conventional pharmacologic therapies. We review some phytomedicines potentially useful for migraine treatment—feverfew (Tanacetum parthenium), butterbur (Petasites hybridus), marijuana (Cannabis spp.), Saint John's Wort (Hypericum perforatum) and the Damask rose (Rosa × damascena)—with respect to their mechanisms of action and evidence for treatment of migraine. The evidence for feverfew is mixed; butterbur is effective with potential risks of hepatotoxicity related to preparation; marijuana has not been shown to be effective in migraine treatment, and data are scant; Saint John's Wort shows relevant physiological activity but is a hepatic enzyme inducer and lacks clinical studies for this purpose; the Damask rose when used in topical preparations did not show efficacy in one clinical trial. Other plant preparations have been considered for migraine treatment but most without blinded randomized, placebo-controlled trial evidence.

http://bit.ly/2CdtDqV

Experimental Study of Thrust Force and Torque for Drilling Cortical Bone

Abstract

Excessive drilling forces can result in drill breakage, bone breakthrough, and thermal necrosis during bone drilling process. However, the effect of drilling process parameters, drill geometry parameters, and bone material type on drilling forces have not been fully investigated. Three designs of experiments are introduced separately to study single factor's effect on drilling forces, identify significant geometry parameters and possible interactions for drilling forces, and formulate direct relationship between drilling forces and process parameters. The results show that thrust force and torque are increased with feed rate, drill diameter or web thickness. The effect of spindle speed, point angle, helix angle, and chisel edge angle on drilling forces is complex. The results also show that the drilling forces are affected by bone type significantly, which are highest for bovine cortical bone, and lowest for Sawbones 3401. The levels of significance of geometry parameters are identified and different for thrust force and torque, which can assist new surgical drill development. Quadratic regression equations obtained by response surface methodology can predict thrust force and torque accurately in a wide range of process parameters, which can be used to control drilling conditions for robot assisted surgeries to realize safe drilling.

http://bit.ly/2TFYN17

An analysis of results in a single-blinded, prospective randomized controlled trial comparing non-fixating versus self-fixating mesh for laparoscopic inguinal hernia repair

Abstract

Background

It remains unclear whether use of self-fixating mesh during laparoscopic inguinal hernia repair (LIHR) impacts postoperative quality of life (QoL). We hypothesize patients receiving self-fixating mesh during totally extraperitoneal (TEP) LIHR will report less pain and improved QoL compared to those receiving non-fixating mesh.

Methods

An IRB-approved, single-blinded randomized controlled trial was conducted. Patients with primary, unilateral inguinal hernias were randomized to receive either non-fixating (control) or self-fixating mesh. Clinical visits were conducted 3 weeks and 1 year after LIHR. A validated Surgical Outcomes Measurement System (SOMS) instrument was used to assess patients' QoL preoperatively and postoperatively along with Carolinas Comfort Scale (CCS) at 3 weeks and 1 year after surgery. Comparisons between self-fixating and non-fixating mesh groups were made using Chi-square, Wilcoxon rank-sum or independent samples t tests.

Results

Two hundred and seventy patients were enrolled (137 non-fixating vs 133 self-fixating). Preoperatively, there was no difference in mean age, BMI, or median hernia duration between groups (57.9 vs 56.6 years, p = 0.550; 26.1 vs 26.8, p = 0.534; 3.0 vs 3.0 months, p = 0.846). Median operative times (34 vs 34 min, p = 0.545) and LOS were similar. More patients in the non-fixating group received tacks (43 vs 19, p = 0.001). Patients receiving non-fixating mesh recorded better mean SOMS scores for the first 3 days following surgery (Day 1: p = 0.005; Day 2: p = 0.002; Day 3: p = 0.024, Table 1) indicating less pain. No differences in pain were seen 3 weeks or 1 year postoperatively. There were zero recurrences found during clinical follow-up in either of the groups.

Conclusions

Patients receiving self-fixating mesh report worse postoperative pain in the first 2–3 days than those receiving non-fixating mesh. The groups showed no differences across QoL metrics (SOMS and CCS) at 3 weeks or 1 year postoperatively. Self-fixating mesh does not appear to positively impact QoL after TEP LIHR.

http://bit.ly/2H4C3GJ

Elimination of surgical drains following robotic-assisted partial nephrectomy

Abstract

To prospectively evaluate outcomes of robotic-assisted partial nephrectomy (RAPN) following elimination of surgical drains. 100 consecutive drainless RAPN performed by a single surgeon were analyzed following a previously published quantitative assessment of drain creatinine/serum creatinine ratios. This cohort was compared to 100 preceding RAPN with drains. Variables analyzed included pre-operative patient/tumor characteristics and post-operative outcomes including post-operative estimated glomerular filtration rate (eGFR), length of hospital stay (LOS), and complications. There was no significant difference in median patient age, sex, body mass index, ASA score, or pre-operative eGFR between the two groups. The preceding 100 patients with drains did have larger median renal size (3.5 vs 2.6 cm, p < 0.001), higher median RENAL scores (9 vs 8, p < 0.001), and longer warm ischemia time (21 vs 18 min, p = 0.004). Patients without drains had shorter median LOS (2.0 days vs 3.0 days, p < 0.001), fewer Grade III or higher post-operative complications (4% vs 10%, p = 0.007), and no difference in 1 month percent change in eGFR (− 13% vs − 11%, p = 0.84). After adjusting for confounding variables there was no difference in LOS (OR 1.50, p = 0.31), Grade III–V complications (OR 1.49, p = 0.63), or 1 month percent change in eGFR (OR 2.3, p = 0.41) between the two groups. One patient in the drainless group required a post-operative drain for a urine leak diagnosed 10 days following RAPN. Omission of drains is safe in RAPN and does not appear to offer a clinical advantage.

http://bit.ly/2TyiQOS

On the Oxidation Behavior and Its Influence on the Martensitic Transformation of Ti–Ta High-Temperature Shape Memory Alloys

Abstract

In the present work, the influence of oxidation on the martensitic transformation in Ti–Ta high-temperature shape memory alloys is investigated. Thermogravimetric analysis in combination with microstructural investigations by scanning electron microscopy and transmission electron microscopy were performed after oxidation at 850 °C and at temperatures in the application regime of 450 °C and 330 °C for 100 h, respectively. At 850 °C, internal oxidation results in the formation of a mixed layered scale of TiO₂ and β-Ta₂O₅, associated with decomposition into Ta-rich bcc β-phase and Ti-rich hexagonal α-phase in the alloy. This leads to a suppression of the martensitic phase transformation. In addition, energy dispersive X-ray analysis suggests an oxygen stabilization of the α-phase. At 450 °C, a slow decomposition into Ta-rich β-phase and Ti-rich α-phase is observed. After oxidation at 330 °C, the austenitic matrix shows strong precipitation of the ω-phase that suppresses the martensitic transformation on cooling.

http://bit.ly/2H3TJCn

Using Infant Mortality Data to Improve Maternal and Child Health Programs: An Application of Statistical Process Control Techniques for Rare Events

Abstract

Introduction The infant mortality rate (IMR) in the United States remains higher than most developed countries. To understand this public health issue and support state public health departments in displaying and analyzing data in ways that support learning, states participating in the Collaborative Improvement and Innovation Network to Reduce Infant Mortality (IM CoIIN) created statistical process control (SPC) charts for rare events. Methods State vital records data on live births and infant deaths was used to create U, T and G charts for Kansas and Alaska, two states participating in the IM CoIIN who sought methods to more effectively analyze IMR for subsets of their populations with infrequent number of deaths. The IMR and the number of days and number of births between infant deaths was charted for Kansas Non-Hispanic black population and six Alaska regions for the time periods 2013–2016 and 2011–2016, respectively. Established empirical patterns indicated points of special cause variation. Results The T and G charts for Kansas and G charts for Alaska depict points outside the upper control limit. These points indicate special cause variation and an increased number of days and/or births between deaths at these time periods. Discussion T and G charts offer value in examining rare events, and indicate special causes not detectable by U charts or other more traditional analytic methods. When small numbers make traditional analysis challenging, SPC has potential in the MCH field to better understand potential drivers of improvements in rare outcomes, inform decision making and take interventions to scale.

http://bit.ly/2TBxftF

Using Infant Mortality Data to Improve Maternal and Child Health Programs: An Application of Statistical Process Control Techniques for Rare Events

Abstract

Introduction The infant mortality rate (IMR) in the United States remains higher than most developed countries. To understand this public health issue and support state public health departments in displaying and analyzing data in ways that support learning, states participating in the Collaborative Improvement and Innovation Network to Reduce Infant Mortality (IM CoIIN) created statistical process control (SPC) charts for rare events. Methods State vital records data on live births and infant deaths was used to create U, T and G charts for Kansas and Alaska, two states participating in the IM CoIIN who sought methods to more effectively analyze IMR for subsets of their populations with infrequent number of deaths. The IMR and the number of days and number of births between infant deaths was charted for Kansas Non-Hispanic black population and six Alaska regions for the time periods 2013–2016 and 2011–2016, respectively. Established empirical patterns indicated points of special cause variation. Results The T and G charts for Kansas and G charts for Alaska depict points outside the upper control limit. These points indicate special cause variation and an increased number of days and/or births between deaths at these time periods. Discussion T and G charts offer value in examining rare events, and indicate special causes not detectable by U charts or other more traditional analytic methods. When small numbers make traditional analysis challenging, SPC has potential in the MCH field to better understand potential drivers of improvements in rare outcomes, inform decision making and take interventions to scale.

http://bit.ly/2TBxftF

Adapting to water impacts of climate change

http://bit.ly/2RC5FiG

Development of peak oxygen uptake from 11–16 years determined using both treadmill and cycle ergometry

Abstract

Purposes

To investigate the development of peak oxygen uptake ( \(\dot{\text{O}}_{2}\) ) assessed on both a treadmill and a cycle ergometer in relation with sex and concurrent changes in age, body mass, fat-free mass (FFM), and maturity status and to evaluate currently proposed 'clinical red flags' or health-related cut-points for peak \(\dot{\text{O}}_{2}\) .

Methods

Multiplicative multilevel modelling, which enables the effects of variables to be partitioned concurrently within an allometric framework, was used to analyze the peak \(\dot{\text{O}}_{2}\) s of 138 (72 boys) students initially aged 11–14 years and tested on three annual occasions. Models were founded on 640 (340 from boys) determinations of peak \(\dot{\text{O}}_{2}\) , supported by anthropometric measures and maturity status.

Results

Mean peak \(\dot{\text{O}}_{2}\) s were 11–14% higher on a treadmill. The data did not meet the statistical assumptions underpinning ratio scaling of peak \(\dot{\text{O}}_{2}\) with body mass. With body mass appropriately controlled for boys' peak \(\dot{\text{O}}_{2}\) s were higher than girls' values and the difference increased with age. The development of peak \(\dot{\text{O}}_{2}\) was sex-specific, but within sex models were similar on both ergometers with FFM the dominant anthropometric factor.

Conclusions

Data should not be pooled for analysis but data from either ergometer can be used independently to interpret the development of peak \(\dot{\text{O}}_{2}\) in youth. On both ergometers and in both sexes, FFM is the most powerful morphological influence on the development of peak \(\dot{\text{O}}_{2}\) . 'Clinical red flags' or health-related cut-points proposed without consideration of exercise mode and founded on peak \(\dot{\text{O}}_{2}\) in ratio with body mass are fallacious.

http://bit.ly/2TB3PMg

Risk Factors for Postpartum Emergency Department Visits in an Urban Population

Abstract

Objectives To identify risk factors associated with urban postpartum emergency department utilization. Methods This case–control study included 100 matched pairs of postpartum women who had delivered at a large, integrated urban medical system in Bronx, New York, in 2012–2013, with the cases having had an emergency department visit within 42 days of delivery. The cases, identified utilizing administrative and billing data, were matched 1:1 with controls by labor unit, delivery mode and date, excluding nonviable pregnancies. The controls did not have a known postpartum emergency department visit. Variables were abstracted from administrative data and chart review, and included demographics, antenatal/intrapartum/postpartum complications and neonatal intensive care unit admission. Factors associated with puerperal emergency department use were identified via univariate and multivariable analyses. Results Following conditional logistic regression, primiparity [54% vs. 32%, aOR 5.91, 95% CI 2.34–14.91], public insurance [70% vs. 56%, aOR 4.22, 95% CI 1.60–11.12], weekend delivery [30% vs. 26%, aOR 7.61, 95% CI 1.15–52.43] and delivery-related complications [47% vs. 28%, aOR 2.95, 95% CI 1.16–7.51] were associated with an increased risk of postpartum emergency department use, while women of younger ages (17–24 years old) were less likely to have postpartum emergency department use [aOR 0.23, 95% CI 0.07–0.74]. Univariate analysis of individual events within the composite variables showed an association between gestational hypertension/pre-eclampsia and postpartum emergency department use [28% vs. 13% OR 2.60, 95% CI 1.26–5.39]. Psychiatric history, social instability, preterm delivery/neonatal intensive care unit admission, pre-existing medical/antepartum conditions and prolonged postpartum stay were not associated. Conclusions for Practice Delivery-related complications, delivery timing, and certain sociodemographic factors are identifiable risk factors for increased postpartum emergency department utilization. These may be targeted for development of interventions improving puerperal care and potentially preventing emergency department visits, which are costly to the health system and disruptive to the lives of women and their families.

http://bit.ly/2VI4aii

Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients

Abstract

Objectives

Low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with a higher frequency of risk factors and cardiovascular disease. The aim of this study is to evaluate the association of 25(OH)D, cardiovascular risk factors, and subclinical atherosclerosis in systemic lupus erythematosus (SLE) patients.

Method

Forty-seven female SLE patients were studied. Data collected included demographics, SLE activity, disease damage, cardiovascular risk factors, and markers of subclinical atherosclerosis. Patient treatments and vitamin D and calcium supplementation (VitD-Ca) were recorded. Vitamin D deficiency was defined as serum 25(OH)D < 50 nmol/l measured by ultra-high-performance liquid chromatography. Atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry and intima-media thickness (IMT) by B-mode ultrasound scanning.

Results

61.7% of patients were vitamin D deficient with a mean level of 31.91 ± 10.21 nmol/l. Serum vitamin D concentration was significantly higher in the 23 patients taking VitD-Ca supplements than that in patients not supplemented (p = 0.004). No significant association was found between 25(OH)D serum levels and cardiovascular risk factors, disease activity, or different treatments for SLE. A significant positive correlation was found between 25(OH)D levels, PWV (p = 0.02), and IMT (p = 0.01); moreover, patients taking VitD-Ca supplements presented an increased arterial stiffness.

Conclusion

Patients with arterial stiffness showed higher levels of serum vitamin D and most of them were on VitD-Ca supplements. Although prospective studies with a larger number of patients and follow-up are needed, our findings suggest that VitD-Ca supplementation may have effects on SLE patients' arterial stiffness.

http://bit.ly/2VI5Xnw

Open-and-Shut Case: An Uncommon Cause of GI Bleeding

http://bit.ly/2FkEvHx

Sessile Serrated Polyps with Synchronous Conventional Adenomas Increase Risk of Future Advanced Neoplasia

Abstract

Background

Surveillance colonoscopy guidelines following adenomas or sessile serrated adenomas/polyps (SSPs) are based on pathology features known to be associated with risk of future colorectal cancer. A synchronous conventional adenoma may increase the malignant potential of SSP, but current guidelines do not address this combination of pathologies.

Aims

The aim was to assess the risk of advanced neoplasia after SSP with or without synchronous adenoma compared to that following a conventional adenoma.

Methods

An audit was conducted on colonoscopies performed between 2000 and 2014 as part of a surveillance program. Index colonoscopy findings were classified as: low-risk SSP and high-risk SSP (size ≥ 10 mm or with cytological dysplasia) with and without synchronous adenoma; high-risk adenoma and low-risk adenoma. Risk of advanced neoplasia was determined at subsequent surveillance colonoscopies.

Results

In total, 2157 patients had adenoma or SSP found at index colonoscopy—low-risk adenoma (40%), high-risk adenoma (54%) and SSP (4%). Synchronous adenomas were seen with 47% of SSP. The median follow-up was 50.3 months (interquartile range 28.1–79.3). Compared to an index finding of low-risk adenoma, index findings of high-risk adenoma, as well as SSP with synchronous adenoma, were independent predictors of future advanced neoplasia (high-risk adenoma: hazard ratio (HR) = 2.04 (95% CI 1.70–2.45); high-risk SSP + adenoma HR = 3.20 (95% CI 1.31–7.82); low-risk SSP + adenoma: HR = 2.20 (95% CI 1.03–4.68)).

Conclusions

Synchronous adenoma increases the risk of advanced neoplasia for SSP equivalent to that seen following high-risk adenoma. Guidelines for surveillance should take into account concurrent pathologies with SSP.

http://bit.ly/2FlOnjm

Hepatic miR-181b-5p Contributes to Glycogen Synthesis Through Targeting EGR1

Abstract

Background/Aim

The miR-181 family plays an important role in the regulation of various cellular functions. However, whether miR-181b-5p mediates hepatic insulin resistance remains unknown. In this study, we investigated the effect of miR-181b-5p on the regulation of hepatic glycogen synthesis.

Methods

The miR-181b-5p levels in the livers of diabetic mice were detected by real-time PCR. The glycogen levels and AKT/GSK pathway activation were examined in human hepatic L02 cells and HepG2 cells transfected with miR-181b-5p mimic or inhibitor. The potential target genes of miR-181b-5p were evaluated using a luciferase reporter assay and Western blot analysis. EGR1-specific siRNA and pCMV-EGR1 were used to further determine the role of miR-181b-5p in hepatic glycogen synthesis in vitro. Hepatic inhibition of miR-181b-5p in mice was performed using adeno-associated virus 8 (AAV8) vectors by tail intravenous injection.

Results

The miR-181b-5p levels were significantly decreased in the serum and livers of diabetic mice as well as the serum of type 2 diabetes patients. Importantly, inhibition of miR-181b-5p expression impaired the AKT/GSK pathway and reduced glycogenesis in hepatocytes. Moreover, upregulation of miR-181b-5p reversed high-glucose-induced suppression of glycogenesis. Further analysis revealed that early growth response 1 (EGR1) was a downstream target of miR-181b-5p. Silencing of EGR1 expression rescued miR-181b-5p inhibition-reduced AKT/GSK pathway activation and glycogenesis in hepatocytes. Hepatic inhibition of miR-181b-5p led to insulin resistance in C57BL/6 J mice.

Conclusion

We demonstrated that miR-181b-5p contributes to glycogen synthesis by targeting EGR1, thereby regulating PTEN expression to mediate hepatic insulin resistance.

http://bit.ly/2FhFgkf

Risk Factors for Postpartum Emergency Department Visits in an Urban Population

Abstract

Objectives To identify risk factors associated with urban postpartum emergency department utilization. Methods This case–control study included 100 matched pairs of postpartum women who had delivered at a large, integrated urban medical system in Bronx, New York, in 2012–2013, with the cases having had an emergency department visit within 42 days of delivery. The cases, identified utilizing administrative and billing data, were matched 1:1 with controls by labor unit, delivery mode and date, excluding nonviable pregnancies. The controls did not have a known postpartum emergency department visit. Variables were abstracted from administrative data and chart review, and included demographics, antenatal/intrapartum/postpartum complications and neonatal intensive care unit admission. Factors associated with puerperal emergency department use were identified via univariate and multivariable analyses. Results Following conditional logistic regression, primiparity [54% vs. 32%, aOR 5.91, 95% CI 2.34–14.91], public insurance [70% vs. 56%, aOR 4.22, 95% CI 1.60–11.12], weekend delivery [30% vs. 26%, aOR 7.61, 95% CI 1.15–52.43] and delivery-related complications [47% vs. 28%, aOR 2.95, 95% CI 1.16–7.51] were associated with an increased risk of postpartum emergency department use, while women of younger ages (17–24 years old) were less likely to have postpartum emergency department use [aOR 0.23, 95% CI 0.07–0.74]. Univariate analysis of individual events within the composite variables showed an association between gestational hypertension/pre-eclampsia and postpartum emergency department use [28% vs. 13% OR 2.60, 95% CI 1.26–5.39]. Psychiatric history, social instability, preterm delivery/neonatal intensive care unit admission, pre-existing medical/antepartum conditions and prolonged postpartum stay were not associated. Conclusions for Practice Delivery-related complications, delivery timing, and certain sociodemographic factors are identifiable risk factors for increased postpartum emergency department utilization. These may be targeted for development of interventions improving puerperal care and potentially preventing emergency department visits, which are costly to the health system and disruptive to the lives of women and their families.

http://bit.ly/2VI4aii

Bedeutung des follikulären Penetrationswegs für den Wirkstofftransport mittels Nanocarriern

Zusammenfassung

Hintergrund

Der Haarfollikel stellt einen bedeutenden Penetrationsweg für topisch applizierte Substanzen dar.

Fragestellung

Die perkutane Absorption von bestimmten Substanzen kann durch die Beteiligung der Haarfollikel deutlich gesteigert und beschleunigt werden. Ferner haben Nanopartikel die Eigenschaft, besonders tief und effektiv in die Haarfollikel hinein zu penetrieren.

Material und Methoden

Dies bietet die Möglichkeit, den Wirkstofftransport für topisch applizierte Substanzen zu optimieren, indem die Nanocarrier allein als Transporter für die Wirkstoffe in den Haarfollikel fungieren. Innerhalb des Haarfollikels muss nach erfolgter Penetration eine Freisetzung des Wirkstoffs vom Nanocarrier erfolgen. Dies kann durch verschiedene Mechanismen getriggert werden.

Ergebnisse

Die freigesetzten Nanocarrier können somit unabhängig vom Nanopartikel in das den Haarfollikel umgebende lebende Gewebe übergehen. Mithilfe dieser innovativen Strategie kann die Bioverfügbarkeit von topisch applizierten Substanzen deutlich verbessert werden.

Schlussfolgerung

Ein Transport von Wirkstoffen in die Haarfollikel mithilfe von Partikeln und die dortige Wirkstofffreisetzung stellen eine sehr effektive neue Methode dar, Wirkstoffe durch die Hautbarriere zu transportieren.

http://bit.ly/2C6FIhe

Genderaspekt bei Angioödemen

Zusammenfassung

Hintergrund

Angioödeme können durch die Mediatoren Bradykinin oder durch Histamin ausgelöst werden. Dabei sind geschlechtsspezifische Unterschiede sowie mögliche Biomarker zur Verlaufskontrolle/Therapieüberwachung weitgehend unbekannt.

Fragestellung

Inwieweit unterscheiden sich, bezogen auf das Geschlecht, Gendefekte, Prodromi, Triggerfaktoren, klinische Parameter wie Attackenzahl, -frequenz, -lokalisation, Laborwerte, Hormone und Therapieansprechen bei den verschiedenen Angioödemtypen.

Material und Methode

Es erfolgten eine Literaturrecherche in PubMed mit den Stichworten „angioedema" und „sex" oder „gender" sowie gezieltes Screening von Übersichtsarbeiten, Leitlinien und Zulassungsstudien mit Angioödem-relevanten Medikamenten.

Ergebnisse

Bei histaminvermittelten Angioödemen sind kaum geschlechtsspezifische Unterschiede zu erkennen. Bei bradykininvermittelten hereditären Angioödemen, insbesondere mit FXII-Mutation, aber auch bei ACE(„angiotensin-converting enzyme")-Inhibitor-bedingten Angioödemen sind Frauen häufiger und stärker betroffen und hormonelle Einflüsse dokumentiert. Auch die Lokalisation der bradykininvermittelten Angioödeme ist genderspezifisch unterschiedlich. Der Anteil der Frauen in Zulassungsstudien bei HAE(hereditäres Angioödem)-Therapien beträgt etwa zwei Drittel.

Schlussfolgerungen

Grundsätzlich scheint eine Differenzierung zwischen östrogenabhängigen, östrogensensitiven und -insensitiven Angioödemen sinnvoll. Die Charakterisierung dieser Untergruppen führt zu einem besseren Verständnis des Pathomechanismus der Hormoneffekte auf die Angioödeme. Dies könnte zur Entwicklung von dringend benötigten Biomarkern für eine schnellere und gezieltere Diagnostik sowie für die Vorhersage von Attacken führen, um mittels individualisierter genderspezifischer Therapie Gesundheit und Lebensqualität der Angioödempatienten signifikant zu verbessern.

http://bit.ly/2Rgu8uu

Nachruf auf Herrn Prof. Dr. Hansotto Zaun

http://bit.ly/2C9yARs

Luftverschmutzung (Feinstaub, Stickstoffdioxid) und Hautalterung

Zusammenfassung

Vor einigen Jahren wurde entdeckt, dass Luftverschmutzung die menschliche Haut altern lässt. Diese Schlussfolgerung gründet auf epidemiologischen und mechanistischen Studien. Konkret tragen Schwebstaubpartikel, aber auch eine Stickstoffdioxidbelastung (NO₂) zu einer verstärkten Pigmentfleckenbildung insbesondere in der Gesichtshaut bei. Genetische Studien haben zudem gezeigt, dass daran auch Gen-Umwelt-Interaktionen beteiligt sind. So weisen Frauen, die bestimmte genetische Varianten des AHR(Arylkohlenwasserstoffrezeptor)-Signalweges aufweisen, ein deutlich erhöhtes Risiko auf, mehr Lentigines auf den Wangen nach einem Anstieg der Schwebstaubbelastung (PM2,5 [Feinstaub mit einem aerodynamischen Durchmesser kleiner als 2,5 µm]) zu entwickeln. Mechanistische Studien belegen einen direkten Zusammenhang zwischen einer topischen Belastung der menschlichen Haut ex vivo sowie in vivo mit umweltrelevanten, nichttoxischen Konzentrationen etablierter Dieselabgasgemische und einer verstärkten Pigmentierung der Haut, die auf einer Melaninneusynthese beruht und durch eine oxidative Stressantwort ausgelöst wird. Entsprechend erweisen sich topisch in kosmetischen Anti-Pollution-Produkten applizierte, ausgewählte Antioxidanzien, aber auch AHR-Antagonisten als geeignet, diese Pigmentierungsreaktion zu reduzieren bzw. zu verhindern. Ein weiterer wichtiger Aspekt ist die mögliche Interaktion von Luftverschmutzungsbestandteilen mit dem natürlichen Sonnenlicht, das ebenfalls zur Hautalterung und zur Pigmentfleckenbildung beiträgt. In einer realen Expositionssituation ist die menschliche Haut simultan beiden Umweltnoxen ausgesetzt. Entsprechende umweltepidemiologische Untersuchungen zeigen, dass in der Troposphäre vorhandener Schwebstaub und solare UV-Strahlung sich gegenseitig beeinflussen und die umweltinduzierte Hautalterung somit ein hochkomplexer Prozess ist.

http://bit.ly/2RgtQDU

Eine seltene Differenzialdiagnose zu odontogenen Abszessen

http://bit.ly/2FjLLm0

The relationship between gait and functional outcomes in patients treated with circular external fixation for malunited tibial fractures

Publication date: Available online 8 January 2019

Source: Gait & Posture

Author(s): Muhammad Ahmed Manjra, Jaco Naude, Franz Birkholtz, Vaida Glatt, Kevin Tetsworth, Erik Hohmann

Abstract

Background

Lower extremity fractures have a profound negative effect on a patient’s gait and outcomes. Correction of deformity, and with it normalization of objective gait parameters, may result in better subjective and objective functional outcomes in patients treated with circular external fixation for malunited tibial fractures.

Aim

The purpose of this study was to investigate the relationships between gait parameters, patient reported outcome measures (PROMs), and health related quality of life measures in patients treated with circular external fixation for the correction of deformity related to tibial malunions.

Methods

This retrospective study included patients with posttraumatic tibial deformities, aged 14 to 65, with a minimum follow-up of 24 months following deformity correction. Patients with congenital deformities, head injuries, spinal cord injury, neurological disorders, or contralateral lower limb amputation were excluded. Functional outcomes were assessed by the Foot Function Index (FFI); Short Form 12 (SF-12); the EQ 5D; and the ASAMI score. Gait analysis was performed using Dartfish® and the Edinburgh Visual Gait Score (EVGS). The relationships between the EVGS and functional outcome scores were analyzed using Pearsons’ moment correlations with Bonferroni corrections.

Results

Eleven patients with a mean age of 42 (range 23-57) were analyzed. The mean EVGS was 2.6+2.1, the mean FFI 29.6+33.4, the mean EQ5 Index Value 0.7+0.2, the mean EQ5 VAS 85.4+19.5, the SF12 mean Physical Component Score (PCS) 46.7+11.1, and the mean Mental Component Score (MCS) 55.2+7.5. The following relationships were strong and significant: EVGS and FFI (r = 0.7; P = 0.02), EVGS and PCS (r=-0.82; P = 0.02), and FFI and EQ5 (r=-0.79, P = 0.05).

Significance

The results of this study suggest that correction of deformity with realignment and restoration of normal anatomy was associated with improved functional outcomes and physical well-being. Patient reported quality of life is strongly associated with patient perceived functional outcome, but not with objective gait parameters.

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The relationship between gait and functional outcomes in patients treated with circular external fixation for malunited tibial fractures

Publication date: Available online 8 January 2019

Source: Gait & Posture

Author(s): Muhammad Ahmed Manjra, Jaco Naude, Franz Birkholtz, Vaida Glatt, Kevin Tetsworth, Erik Hohmann

Abstract

Background

Lower extremity fractures have a profound negative effect on a patient's gait and outcomes. Correction of deformity, and with it normalization of objective gait parameters, may result in better subjective and objective functional outcomes in patients treated with circular external fixation for malunited tibial fractures.

Aim

The purpose of this study was to investigate the relationships between gait parameters, patient reported outcome measures (PROMs), and health related quality of life measures in patients treated with circular external fixation for the correction of deformity related to tibial malunions.

Methods

This retrospective study included patients with posttraumatic tibial deformities, aged 14 to 65, with a minimum follow-up of 24 months following deformity correction. Patients with congenital deformities, head injuries, spinal cord injury, neurological disorders, or contralateral lower limb amputation were excluded. Functional outcomes were assessed by the Foot Function Index (FFI); Short Form 12 (SF-12); the EQ 5D; and the ASAMI score. Gait analysis was performed using Dartfish® and the Edinburgh Visual Gait Score (EVGS). The relationships between the EVGS and functional outcome scores were analyzed using Pearsons' moment correlations with Bonferroni corrections.

Results

Eleven patients with a mean age of 42 (range 23-57) were analyzed. The mean EVGS was 2.6+2.1, the mean FFI 29.6+33.4, the mean EQ5 Index Value 0.7+0.2, the mean EQ5 VAS 85.4+19.5, the SF12 mean Physical Component Score (PCS) 46.7+11.1, and the mean Mental Component Score (MCS) 55.2+7.5. The following relationships were strong and significant: EVGS and FFI (r = 0.7; P = 0.02), EVGS and PCS (r=-0.82; P = 0.02), and FFI and EQ5 (r=-0.79, P = 0.05).

Significance

The results of this study suggest that correction of deformity with realignment and restoration of normal anatomy was associated with improved functional outcomes and physical well-being. Patient reported quality of life is strongly associated with patient perceived functional outcome, but not with objective gait parameters.

from #Audiology via ola Kala on Inoreader http://bit.ly/2LZElFO

The relationship between gait and functional outcomes in patients treated with circular external fixation for malunited tibial fractures

Publication date: Available online 8 January 2019

Source: Gait & Posture

Author(s): Muhammad Ahmed Manjra, Jaco Naude, Franz Birkholtz, Vaida Glatt, Kevin Tetsworth, Erik Hohmann

Abstract

Background

Lower extremity fractures have a profound negative effect on a patient’s gait and outcomes. Correction of deformity, and with it normalization of objective gait parameters, may result in better subjective and objective functional outcomes in patients treated with circular external fixation for malunited tibial fractures.

Aim

The purpose of this study was to investigate the relationships between gait parameters, patient reported outcome measures (PROMs), and health related quality of life measures in patients treated with circular external fixation for the correction of deformity related to tibial malunions.

Methods

This retrospective study included patients with posttraumatic tibial deformities, aged 14 to 65, with a minimum follow-up of 24 months following deformity correction. Patients with congenital deformities, head injuries, spinal cord injury, neurological disorders, or contralateral lower limb amputation were excluded. Functional outcomes were assessed by the Foot Function Index (FFI); Short Form 12 (SF-12); the EQ 5D; and the ASAMI score. Gait analysis was performed using Dartfish® and the Edinburgh Visual Gait Score (EVGS). The relationships between the EVGS and functional outcome scores were analyzed using Pearsons’ moment correlations with Bonferroni corrections.

Results

Eleven patients with a mean age of 42 (range 23-57) were analyzed. The mean EVGS was 2.6+2.1, the mean FFI 29.6+33.4, the mean EQ5 Index Value 0.7+0.2, the mean EQ5 VAS 85.4+19.5, the SF12 mean Physical Component Score (PCS) 46.7+11.1, and the mean Mental Component Score (MCS) 55.2+7.5. The following relationships were strong and significant: EVGS and FFI (r = 0.7; P = 0.02), EVGS and PCS (r=-0.82; P = 0.02), and FFI and EQ5 (r=-0.79, P = 0.05).

Significance

The results of this study suggest that correction of deformity with realignment and restoration of normal anatomy was associated with improved functional outcomes and physical well-being. Patient reported quality of life is strongly associated with patient perceived functional outcome, but not with objective gait parameters.

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Adapting the 2015 Mother–Baby Friendly Birth Facility Guidelines for Semi-nomadic Pastoralist Communities in Laikipia and Samburu Counties of Kenya

Abstract

Purpose To adapt the 2015 International Federation of Gynecologists and Obstetricians (FIGO), International Confederation of Midwives (ICM), White Ribbon Alliance (WRA), International Pediatric Association (IPA), and WHO auspiced Guidelines on Mother–Baby Friendly Facilities to a particular sub-population; seminomadic pastoralist communities of Laikipia and Samburu Counties, Kenya. We anticipate an increased utilization of childbirth services by improving their acceptability. Description We drafted a Pastoralist Friendly Birthing Facility Checklist based on the FIGO/ICM/WRA/IPA/WHO guidelines and previous research in this context. We employed mixed methods to finalise the adaptation: a workshop with 27 local stakeholders; interviews with ten health planners and skilled birth attendants (SBAs); and ten focus group discussions (FGDs) with health committee members, community health workers, mothers and traditional birth attendants (TBAs). A facility audit of dispensaries across five group ranches was also undertaken. Assessment The final Checklist was divided into: characteristics of care and the environment; care during labour and birth; post-partum care; and community staff relationships. It was endorsed by the Ministries of Health in the relevant counties, and by women, SBAs and TBAs. No facility currently satisfies all the criteria specified in the Checklist. Conclusion The FIGO/ICM/WRA/IPA/WHO Guidelines were successfully adapted and can be used to ensure health facilities meet the needs of pastoralist women.

http://bit.ly/2FkK087

Adapting the 2015 Mother–Baby Friendly Birth Facility Guidelines for Semi-nomadic Pastoralist Communities in Laikipia and Samburu Counties of Kenya

Abstract

Purpose To adapt the 2015 International Federation of Gynecologists and Obstetricians (FIGO), International Confederation of Midwives (ICM), White Ribbon Alliance (WRA), International Pediatric Association (IPA), and WHO auspiced Guidelines on Mother–Baby Friendly Facilities to a particular sub-population; seminomadic pastoralist communities of Laikipia and Samburu Counties, Kenya. We anticipate an increased utilization of childbirth services by improving their acceptability. Description We drafted a Pastoralist Friendly Birthing Facility Checklist based on the FIGO/ICM/WRA/IPA/WHO guidelines and previous research in this context. We employed mixed methods to finalise the adaptation: a workshop with 27 local stakeholders; interviews with ten health planners and skilled birth attendants (SBAs); and ten focus group discussions (FGDs) with health committee members, community health workers, mothers and traditional birth attendants (TBAs). A facility audit of dispensaries across five group ranches was also undertaken. Assessment The final Checklist was divided into: characteristics of care and the environment; care during labour and birth; post-partum care; and community staff relationships. It was endorsed by the Ministries of Health in the relevant counties, and by women, SBAs and TBAs. No facility currently satisfies all the criteria specified in the Checklist. Conclusion The FIGO/ICM/WRA/IPA/WHO Guidelines were successfully adapted and can be used to ensure health facilities meet the needs of pastoralist women.

http://bit.ly/2FkK087

Social Support During Pregnancy Modifies the Association Between Maternal Adverse Childhood Experiences and Infant Birth Size

Abstract

Introduction Adverse childhood experiences (ACEs) can deleteriously affect health, including pregnancy and birth outcomes occurring later in life. Identification of modifiable factors during pregnancy that buffer the ill effects of adversity is warranted. Social support during pregnancy can promote better birth outcomes, yet it is unknown whether it could also mitigate perinatal risks stemming from ACEs. Thus, this study considers multiple forms of social support in pregnancy as modifiers of an ACEs and fetal growth association. Methods Data were collected from mother and infant pairs from an ongoing prospective birth cohort. Women enrolled around 27 weeks gestation and completed gold-standard assessments of ACEs and social support. Infant cephalization index scores [(head circumference /birthweight) × 100; a marker of asymmetric fetal growth] were derived. Multivariable regression models tested main effects and interaction between ACEs and social support in relation to infant cephalization. Results Higher levels of ACEs were associated with higher cephalization scores (β = 0.01, SE = 0.01, p < 0.05) whereas higher social support was associated with lower cephalization scores (β = − 0.03, SE = 0.01, p < 0.05). A significant interaction was observed showing a protective effect of social support among those with low (0 events) and moderate (1–3 events) ACEs but not among those with high ACEs (4 + events; p < 0.05). Tangible and emotional support, but not information support, contributed to the associations. Discussion Maternal ACEs can deleteriously affect birth size, yet social support during pregnancy provides some buffer from its enduring effects. Interventions designed to enhance pregnancy social support may not only improve maternal wellbeing, but may also safeguard infant health.

http://bit.ly/2FfUYfP

Electrocochleography: Cochlear Implants and the Return to the Operating Room.

Related Articles

Electrocochleography: Cochlear Implants and the Return to the Operating Room.

J Am Acad Audiol. 2019 Jan;30(1):4-5

Authors: McCaslin DL, Saoji AA

PMID: 30620705 [PubMed - in process]

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Electrocochleography: Cochlear Implants and the Return to the Operating Room.

Related Articles

Electrocochleography: Cochlear Implants and the Return to the Operating Room.

J Am Acad Audiol. 2019 Jan;30(1):4-5

Authors: McCaslin DL, Saoji AA

PMID: 30620705 [PubMed - in process]

from #Audiology via ola Kala on Inoreader http://bit.ly/2FgDnV5
via IFTTT

Electrocochleography: Cochlear Implants and the Return to the Operating Room.

Related Articles

Electrocochleography: Cochlear Implants and the Return to the Operating Room.

J Am Acad Audiol. 2019 Jan;30(1):4-5

Authors: McCaslin DL, Saoji AA

PMID: 30620705 [PubMed - in process]

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via IFTTT

Impact of Oral-Cecal Transit Time on the Interpretation of Lactulose Breath Tests After RYGB: a Personalized Approach to the Diagnosis of SIBO

Abstract

Background

Traditionally, small intestinal bacterial overgrowth (SIBO) is diagnosed when there is an early peak in breath hydrogen or methane. Given unclear intestinal transit time in Roux-en-Y gastric bypass (RYGB) patients, it is unknown if the traditional approach at diagnosing SIBO is adequate in this patient population.

Aim

To assess oral-cecal transit time (OCTT) and its impact on the interpretation of breath tests in the diagnosis of SIBO in patients with RYGB.

Methods

This study was a retrospective review of prospectively collected data on RYGB patients who underwent testing for SIBO using lactulose breath test (LBT) with or without small bowel follow-through (SBFT) to assess OCTT. Outcomes of SIBO test based on LBT alone versus LBT with OCTT were compared using a chi-squared test.

Results

Sixty-two of the 151 RYGB patients who underwent LBT underwent an additional SBFT to assess OCTT. Median OCTT was 60 min. Of these, 59.7% had OCTT shorter than 90 min. Based on LBT alone, 36/62 patients (58.1%) were classified as positive SIBO. When LBT results were combined with OCTT, 26/36 patients (72.2%) had hydrogen or methane rise within OCTT, suggesting 27.8% false positive rate. Patients with true positive SIBO based on LBT and OCTT had a higher response rate to antibiotics compared to those with false positive SIBO (78.3% vs. 33.3%, p = 0.03).

Conclusion

A personalized approach of combining LBT with SBFT to assess OCTT may improve the accuracy of SIBO testing and enhance clinical outcomes in patients with RYGB.

http://bit.ly/2SFA7pk

Outcome of Primary Obesity Surgery Endolumenal Procedure as Obesity Treatment in Private Practice Setting: an Intervention Study

http://bit.ly/2ADKfbn

A robotic teaching session: separating tool from technique to emphasize a cognitive focused teaching environment

Abstract

Most robotic curriculum requires simulation on a console prior to operative exposure. This practice does not permit experiencing the physical collisions with the robotic tools, which occurs during surgery. We designed and evaluated an innovative curriculum to address cognitive components and trouble-shoot robotic collisions when the surgeon lacks haptic feedback. We adapted our previous curriculum, designed to teach and document proficiency of robotic docking and instrument exchange, to include robotic collisions. Participants received a 10-min, didactic presentation describing finger grips, internal and external collisions, and instruction on how to trouble-shoot each type. Residents worked in pairs, one at the console and the other at bedside, to complete two simulation exercises. Participants manipulated the robot to determine how best to resolve the situations. Residents completed retrospective post-course surveys and instructors completed a final survey. For comparison, non-participants, PGY-matched surgical trainees, also completed a survey. All participants demonstrated proficiency in docking and instrument exchange. Compared to pre-session, post-session knowledge and confidence improved in five domains reflecting session objectives (p < 0.05). Participants could list and troubleshoot collisions more than the non-participant matched peers (p < 0.05). Instructors supported the additional collision components, but noted learners needed more time. Two of three non-participants expressed interest in a teaching session to address these components. Collisions occur using robotic technology and rarely get addressed in surgical training. We describe an opportunity for surgeons to trouble-shoot robotic collisions in a safe, simulated environment. This easily transferable curriculum represents one of the first industry-independent robotic teaching sessions for surgical trainees.

http://bit.ly/2QAIdxA

Calcined Eggshell as a P Reactive Media Filter—Batch Tests and Column Sorption Experiment

Abstract

The goal of the study was to assess the sorption properties of calcined eggshells (CEs) as a P reactive media filter. The CEs were calcined in a temperature of 900 °C. A double stage test was performed: batch studies (kinetic and equilibrium) and small-scale column experiment. The estimation of optimal mass ratio of CEs for perspective usage was the additional benefit of column experiment. The short kinetic tests showed that 5 min of contact time with solution of initial concentration of 6.020 mgP-PO₄ L⁻¹ is enough to reduce the P-PO₄ in 100%. The equilibrium studies were conducted with P-PO₄ solution of 6.020 to 977.7 mg L⁻¹ with contact time of 30 min. The obtained data was compensated by non-linear regression using the Marquardt algorithm in the Statgraphics Centurion XVI. The eggshell calcined characterized by high sorption capacity (S_max = 72.87 mg g⁻¹) obtained from the Langmuir isotherm model with a good fit (96.77%). To choose the appropriate ratio of a sand filter to eggshells amendment, four small columns were constructed and fed with P-PO₄ solution (C_in ≈ 5 mg L⁻¹). The percentage mass (m/m) of CEs in the columns was 0.0 (the reference one); 1.0; 2.5; and 5.0. The unit sorption obtained during 95 days of column experiment was 10.668, 4.277, and 2.286 mg P-PO₄ g⁻¹ for 1.0, 2.5, and 5.0%, respectively. For practical implementation, the most recommended addition seems to be 1% of CEs. It corresponds, e.g., to the mass of 49 kg CEs for septic tank system.

http://bit.ly/2FhznE0

Effects of Surfactant and Electrolyte Concentrations, Cation Valence, and Temperature on Graphene Oxide Retention and Transport in Saturated Porous Media

Abstract

Environmental fate and impacts of graphene oxide (GO) nanoparticles are strongly influenced by their subsurface behaviors. The present work examined the aggregation and transport behaviors of GO in saturated sand columns under different temperature (6 and 24 °C), surfactant concentration (0.04% and 0.4%), cation valence, and electrolyte concentration conditions. In monovalent electrolyte (NaCl), although the presence of cationic surfactant (CTAB) notably increased GO stability and mobility, GO ripening happened due to their concurrent aggregation and transport in the columns. GO particles were more mobile at a lower temperature probably because the CTAB coating of GO increased with decreasing temperature, leading to stronger electrostatic repulsion. Furthermore, GO retention in the media increased with the increase of NaCl concentration due to the enhanced compression of the electric double layer. In multivalent electrolyte (CaCl₂ or AlCl₃), the presence of CTAB greatly improved GO stability and mobility and no deposition occurred in saturated porous media under all the tested conditions. This is because the CTAB coating of GO diminished the cation bridging effects in both GO-GO and GO-sand systems. Results from extended Derjaguin–Landau–Verwey–Overbeek (XDLVO) theory considering steric repulsion suggest that secondary minimum aggregation and depositions were the main mechanisms of GO retention transport in monovalent electrolyte in saturated porous media.

http://bit.ly/2FkuNDW

Expression of the VP1 protein of FMDV integrated chromosomally with mutant Listeria monocytogenes strain induced both humoral and cellular immune responses

Abstract

Live vector-based vaccine is a modern approach to overcome the drawbacks of inactivated foot-and-mouth disease (FMD) vaccines such as improper inactivation during manufacture. Listeria monocytogenes (LM), an intracellular microorganism with immune-stimulatory properties, is appropriate to be utilized as a live bacterial vaccine vector. FMDV-VP1 protein has the capability to induce both cellular and humoral immune responses since it is considered the most immunogenic part of FMDV capsid and has the most of antigenic sites for viral neutralization. The codon-optimized vp1 gene was ligated to the integrative pCW702 plasmid to construct the target cassette. The antigen cassette was integrated successfully into the chromosome of mutant LM strain via homologous recombination for more stability to generate a candidate vaccine strain LM△actAplcB-vp1. Safety evaluation of recombinant LM△actAplcB-vp1 revealed it could be eliminated from the internal organs within 3 days as a safe candidate vaccine. Mice groups were immunized I.V. twice with the recombinant LM△actAplcB-vp1 at an interval of 2 weeks. Antigen-specific IgG antibodies and the level of CD4+- and CD8+-specific secreted cytokines were estimated to evaluate the immunogenicity of the candidate vaccine. The rapid onset immune response was detected, strong IgG humoral immune response within 14 days post immunization and augmented again after the booster dose. Cellular immunity data after 9 days post the prime dose indicated elevation in CD4+ and CD8+ secreted cytokine level with another elevation after the booster dose. This is the first report to explain the ability of attenuated mutant LM to be a promising live vector for FMDV vaccine.

http://bit.ly/2FmKk67