A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma

Summary

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6–82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.

https://ift.tt/2PNdhKm

MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells

Summary

Plants are important sources of biologically active compounds and they provide unlimited opportunities for the discovery and development of new drug leads, including new chemotherapeutics. Miconidin acetate (MA) is a hydroquinone derivative isolated from E. hiemalis. In this study we demonstrated that MA was cytotoxic against acute leukemia (AL), solid tumor cells and cancer stem cells, with the strongest effect exhibited against AL. Furthermore, it was non-cytotoxic against non-tumor cells and did not cause significant hemolysis. MA blocks the G2/M phase and causes cytostatic effects, acting in a similar way to dexamethasone by increasing PML expression. The compound also triggered intrinsic and extrinsic apoptosis by modulating Bax, FasR and survivin expression. This led to an extensive mitochondrial damage that resulted in AIF, cytochrome c and endonuclease G release, caspase-3 and PARP cleavage and DNA fragmentation. We have further demonstrated that MA was strongly cytotoxic against neoplastic cells collected from patients with different AL subtypes. Interestingly, MA increased the cytotoxic effect of chemotherapeutics cytarabine and vincristine. This study indicates that MA may be a new agent for AL and highlights its potential as a new source of anticancer drugs.

Graphical abstract

MA blocks G2/M phase with PML expression and KI67 inhibition, ROS generation and intrinsic and extrinsic apoptosis, leading to mitochondrial damage, caspase 3 and PARP cleavage and DNA fragmentation.

https://ift.tt/2UUAP3K

Correction to: Photobiomodulation with single and combination laser wavelengths on bone marrow mesenchymal stem cells: proliferation and differentiation to bone or cartilage

In the originally published article, the name of the 3rd and 4th authors were labeled incorrectly. The correct names are Mohammadreza Baghaban Eslaminejad and Leila Taghiyar. Also, affiliation 4 has been corrected.

https://ift.tt/2Brs8ET

The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical. Herein, a scorpion venom peptide (Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76 (rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon (IFN)-β. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-β by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection. This mechanism is significantly different from traditional virucidal antimicrobial peptides (AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-I IFN responses, demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.

https://ift.tt/2PNh9Lo

Influence of Human Papillomavirus E7 Oncoprotein on Maturation and Function of Plasmacytoid Dendritic Cells In Vitro

Abstract

The major difficulties of human papillomavirus (HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells (pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC.

https://ift.tt/2UTdOxT

The D253N Mutation in the Polymerase Basic 2 Gene in Avian Influenza (H9N2) Virus Contributes to the Pathogenesis of the Virus in Mammalian Hosts

Abstract

Mutations in the polymerase basic 2 (PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence (NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses. However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.

https://ift.tt/2PNKiG0

New Forward Kinematic Model of Parallel Robot Par4

Abstract

Modeling parallel robots is a famous problem of research especially the Forward Kinematic Model (FKM). It is very difficult to solve it compared to serial manipulators and it is also hard to obtain its analytic solution. Most researchers have resorted to the numerical methods. But, these have a lot of problems : the divergence caused by the bad choice of the initial condition and providing more than one feasible solution. To solve these problems, an analytical method is proposed in this article. In this paper, the FKM of the parallel robot Par4 is determined using the Modified Denavit Hartenberg Method (MDHM). This method facilitates greatly the forward kinematic problem of parallel robot. The MDHM is powerful, useful and can be easily used for the closed loop robots. It is very accurate and provides a unique solution. In the best of our knowledge, the MDHM isn't applied to the parallel robot Par4 to give a relationship between its operational and articular variables. After a short presentation of the robot Par4, the FKM is determined using the MDHM method. The results of this method will be compared to the existing numerical method like the iterative Newton method (INM).

https://ift.tt/2ExGFCq

Endovascular treatment for unruptured aneurysm associated with persistent primitive trigeminal artery: a case report and literature review

Abstract

The persistent primitive trigeminal artery (PPTA) is the most common carotid-basilar anastomosis, and the incidence of cerebral aneurysms associated with the PPTA is approximately 4%. Since PPTA aneurysms often have a wide neck and other vascular anomalies, endovascular treatment using an adjunctive technique is the current first-line therapy. Here, we report a case of PPTA aneurysm treated by coil embolization with a stent-assisted technique. A detailed evaluation of the size and course of all vessels and collateral flow, including the Allcock test and balloon test occlusion, is necessary when deciding on the treatment strategy.

https://ift.tt/2QDjP3x

Unsteady Free Convection Boundary Layer Flows of a Bingham Fluid in Cylindrical Porous Cavities

Abstract

We consider two unsteady free convection flows of a Bingham fluid when it saturates a porous medium contained within a vertical circular cylinder. The cylinder is initially at a uniform temperature, and such flows are then induced by suddenly applying either a new constant temperature or a nonzero heat flux to the exterior surface. As time progresses, heat conducts inwards and this may or may not overcome the yield threshold for flow. For the constant temperature case, flow begins immediately should the parameter, Rb, which is a nondimensional yield parameter, be sufficiently large. The ultimate fate, though, is full immobility as the cylinder eventually tends towards a new constant temperature. For the constant heat flux case, the fluid remains immobile but will begin to flow eventually should Rb be sufficiently large. The two cases have different critical values for Rb.

https://ift.tt/2A7tOna

Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Response in rheumatoid arthritis

Abstract

The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: − 3.53, minimum: − 6.77; maximum: + 0.48) and CZP 200 mg (median: − 3.13, minimum: − 6.37; maximum: − 0.52) compared to the methotrexate group (median − 2.41, minimum: − 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: − 0.009 g/cm², minimum: − 0.059 g/cm²; maximum: + 0.095 g/cm²) and CZP 400 mg (median: − 0.008 g/cm², minimum: − 0.064 g/cm²; maximum: + 0.080 g/cm²). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: − 0.024 g/cm², minimum: − 0.102 g/cm²; maximum: + 0.057 g/cm²). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.

https://ift.tt/2LpHwX3

Z-plasty as an alternative choice for the treatment of recurrent local sternal wound infections

Abstract

Objective

Sternal wound infections after sternotomy are associated with high morbidity, high mortality, and prolonged hospital stay. The recurrence rate of sternal wound infections after single-stage closure is greater than expected. The aim of the study is to present our results of a consecutive series of Z-plasty for the treatment of recurrent sternal wound infections.

Methods

Between March 2015 and March 2017, a total of 9 patients were referred to our clinic with a recurrent sternal wound infection due to sternotomy with or without osteomyelitis. All patients previously underwent one or more surgical procedures for sternal infection. Negative pressure wound therapy and several debridement methods were performed before reconstruction. Two triangular double-transposition fasciocutaneous flap techniques as Z-plasty under local anesthesia was performed for all of the patients.

Results

The flaps survived completely without any tissue loss. There were no major postoperative complications. One patient had recurrent infection after the flap procedure and was treated with antibiotic therapy. At 6 months of follow-up, all of the patients were able to return to normal activities of daily living with a high patient satisfaction rate.

Conclusions

Local sternal wound reconstruction is an effective, rapid, and simple with Z-plasty associated with low recurrence risk. We believe that Z-plasty can be used for recurrent local sternal wound infections as an alternative treatment option for selected patients without mechanical dehiscence.

https://ift.tt/2S98PHD

Obesity Is Associated with Increased Risk of Colectomy in Inflammatory Bowel Disease Patients Hospitalized with Clostridium difficile Infection

Abstract

Background

Obesity and inflammatory bowel disease (IBD) are associated with increased risk of Clostridium difficile infection (CDI). The effect of obesity on IBD course and development of complications is poorly understood. We performed this study to examine the effect of obesity on CDI-related morbidity and mortality in hospitalized patients with IBD.

Methods

We used data from the National Inpatient Sample across five study years (2010–2014) to identify patients ≥ 18 years hospitalized with both CDI and IBD. We compared the outcomes of in-hospital mortality, partial or total colectomy, hospital length of stay, and hospital charges between obese and non-obese IBD–CDI patients. Analysis included univariate and multivariate linear and logistic regression analyses.

Results

Of 304,298 hospitalized patients with IBD, 13,517 (4.4%) patients had CDI. Of these, 996 (7.4%) patients were obese. Obese IBD–CDI patients had a higher risk of colectomy (adjusted odds ratio, AOR 1.60, 95% CI 1.30–1.96; p < 0.001), longer hospital length of stay (difference 0.8 days, 95% CI 0.02–1.58; p = 0.04), and higher hospital charges (difference $11,051, 95% CI 1939–20,163; p = 0.02) than non-obese IBD–CDI patients, but no significant difference in mortality was found between the two groups.

Conclusions

Obesity is associated with a 60% increase in the risk of colectomy, longer hospital stay, and higher charges in IBD patients hospitalized with CDI. Further epidemiological and clinical studies are needed to confirm these findings.

https://ift.tt/2BrpfUz

A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma

Summary

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6–82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.

https://ift.tt/2PNdhKm

MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells

Summary

Plants are important sources of biologically active compounds and they provide unlimited opportunities for the discovery and development of new drug leads, including new chemotherapeutics. Miconidin acetate (MA) is a hydroquinone derivative isolated from E. hiemalis. In this study we demonstrated that MA was cytotoxic against acute leukemia (AL), solid tumor cells and cancer stem cells, with the strongest effect exhibited against AL. Furthermore, it was non-cytotoxic against non-tumor cells and did not cause significant hemolysis. MA blocks the G2/M phase and causes cytostatic effects, acting in a similar way to dexamethasone by increasing PML expression. The compound also triggered intrinsic and extrinsic apoptosis by modulating Bax, FasR and survivin expression. This led to an extensive mitochondrial damage that resulted in AIF, cytochrome c and endonuclease G release, caspase-3 and PARP cleavage and DNA fragmentation. We have further demonstrated that MA was strongly cytotoxic against neoplastic cells collected from patients with different AL subtypes. Interestingly, MA increased the cytotoxic effect of chemotherapeutics cytarabine and vincristine. This study indicates that MA may be a new agent for AL and highlights its potential as a new source of anticancer drugs.

Graphical abstract

MA blocks G2/M phase with PML expression and KI67 inhibition, ROS generation and intrinsic and extrinsic apoptosis, leading to mitochondrial damage, caspase 3 and PARP cleavage and DNA fragmentation.

https://ift.tt/2UUAP3K

Evaluation of lung transplant perfusion using iodine maps from novel spectral detector computed tomography

p. 436
Nils Große Hokamp, Amit Gupta
DOI:10.4103/ijri.IJRI_35_18  
We report the case of a 51-year-old patient who underwent bilateral lung transplantation and presented with an unstable condition and sepsis 6 days after transplantation. The performed contrast enhanced spectral detector computed tomography (CT) using a dual-layer detector showed absence of perfusion in the left lung on iodine maps, although branches of the pulmonary artery were patent. This prompted retrospective evaluation of CT images and total venous occlusion of the left pulmonary veins was found. Here, iodine maps helped in raising conspicuity of loss of lung perfusion.
http://www.ijri.org/currentissue.asp?sabs=y

Pulmonary atresia and ventricular septal defect,Coronary artery as the primary source of pulmonary blood flow

Collateral or fistula? Coronary artery as the primary source of pulmonary blood flow in a patient with pulmonary atresia and ventricular septal defect p. 433
Anurag Yadav, Salil Bhargava, T B S Buxi, Krishna Sirvi
DOI:10.4103/ijri.IJRI_489_17  
In patients with pulmonary atresia and ventricular septal defect (PA/VSD), a coronary artery being the primary source of pulmonary blood flow is a rare entity. We describe two cases of PA/VSD with coronary-to-pulmonary artery fistula with emphasis on the role of Computed Tomographic Angiography (CTA) in depicting all the sources of pulmonary blood supply, to predict surgical management and need for unifocalization of Major Aortopulmonary Collateral Arteries (MAPCA's).
http://www.ijri.org/currentissue.asp?sabs=y

An accurate tool to detect cardiac amyloidosis

Myocardial nulling pattern in cardiac amyloidosis on time of inversion scout magnetic resonance imaging sequence – A new observation of temporal variability p. 427
Harshavardhan Mahalingam, Binita Riya Chacko, Aparna Irodi, Elizabeth Joseph, Leena R Vimala, Viji Samuel Thomson
DOI:10.4103/ijri.IJRI_84_18  
Context: The pattern of myocardial nulling in the inversion scout sequence [time of inversion scout (TIS)] of cardiac magnetic resonance imaging (MRI) is an accurate tool to detect cardiac amyloidosis. The pattern of nulling of myocardium and blood at varying times post gadolinium injection and its relationship with left ventricular mass (LVM) in amyloidosis have not been described previously. Aims: The aim is to study the nulling pattern of myocardium and blood at varying times in TIS and assess its relationship with LVM and late gadolinium enhancement (LGE) in amyloidosis. Materials and Methods: This was a retrospective study of 109 patients with clinical suspicion of cardiac amyloidosis who underwent MRI. Of these, 30 had MRI features of amyloidosis. The nulling pattern was assessed at 5 (TIS5min) and 10 (TIS10min) minutes (min) post contrast injection. Nulling pattern was also assessed at 3min (TIS3min) in four patients and 7min (TIS7min) in five patients. Myocardial mass index was calculated. Mann-Whitney U test was done to assess statistical difference in the myocardial mass index between patients with and without reversed nulling pattern (RNP) at TIS5min. Results: RNP was observed in 58% at TIS5minand 89.6% at TIS10min. Myocardial mass index was significantly higher in patients with RNP at TIS5min[mean = 94.87 g/m2; standard deviation (SD) =17.63) when compared with patients with normal pattern (mean = 77.61 g/m2; SD = 17.21) (U = 18; P = 0.0351). Conclusion: In cardiac amyloidosis, TIS sequence shows temporal variability in nulling pattern. Earlier onset of reverse nulling pattern shows a trend toward more LVM and possibly more severe amyloid load.
http://www.ijri.org/currentissue.asp?sabs=y

Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice

Abstract

Introduction

Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes.

Methods

Using national claims databases (2012–2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages.

Results

The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1–4 (Q1–Q4) of follow-up, and had lower SA and all-cause total costs in Q2–Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (− $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (− $640 for SA and − $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (− $794 for SA and − $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups.

Conclusions

Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR.

Funding

Pfizer, Inc.

https://ift.tt/2Bu0uY5

Gujarati hypertensives

: A cross-sectional study p. 153
Jayesh Dalpatbhai Solanki, Hemant B Mehta, Sunil J Panjwani, Hirava B Munshi, Chinmay J Shah
DOI:10.4103/jpp.JPP_59_18  
Objective: To study the effect of different classes and combinations of antihypertensive agents on arterial stiffness and central hemodynamic parameters. Materials and Methods: A cross-sectional study was conducted in 446 treated apparently healthy hypertensives. Oscillometric PWA was performed by Mobil-o-Graph (IEM, Germany) to derive cardiovascular parameters that were further analyzed in groups stratified by antihypertensive used. Study parameters were brachial hemodynamics (blood pressure (BP), heart rate, and rate pressure product); arterial stiffness (augmentation pressure, augmentation index, pulse wave velocity, total arterial stiffness, and pulse pressure amplification); and central hemodynamics (central BP, cardiac output, and stroke work). Statistical significance was kept at P < 0.05. Results: All groups were selected by matching of age, gender, and body mass index. They were comparable with major confounding factors. There was no difference between study parameters in hypertensives taking exclusive angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), or angiotensin II receptor blocker. Multitherapy showed better hemodynamics and monotherapy showed better stiffness parameters. Addition of CCB to ACEI did not make a difference except with diastolic BP. For most comparisons, most of the results lacked statistical significance. Conclusion: Discrete PWA parameters showed no class difference in hypertensives, treated by conventional monotherapy or combination, ACEI appears to be the best drug. This also indicates that early diagnosis and blood pressure control are more important than antihypertensive used.
http://www.jpharmacol.com/currentissue.asp?sabs=y

contrast media-induced nonrenal adverse drug reactions

contrast media-induced nonrenal adverse drug reactions over the last three decades: A systematic review p. 131
Maurizio Sessa, Claudia Rossi, Annamaria Mascolo, Antonella Scafuro, Rosanna Ruggiero, Gabriella di Mauro, Salvatore Cappabianca, Roberto Grassi, Liberata Sportiello, Concetta Rafaniello
DOI:10.4103/jpp.JPP_92_18  
The aim of this study was to investigate the scientific contribution of Italian clinical research for contrast media-induced nonrenal adverse drug reactions over the last three decades. Ovid Embase, Ovid MEDLINE, Web of Science, and Cochrane Methodology Register were used as data sources to identify Italian descriptive studies, observational studies, meta-analyses, and clinical trials assessing contrast media-induced nonrenal adverse drug reactions as a safety outcome. The population of interest was men and women exposed to a contrast medium. Between 1990 and 2017, 24 original articles investigating contrast-induced nonrenal adverse drug reactions were identified. The cohort study was the most representative study design (10/24; 41.7%). The 24 studies were conducted mainly as monocenter studies (14/24; 58.3%) and without receiving funding (17/24; 70.8%). Seventeen out of 24 studies provided a level of evidence ranging from III-2 (11/24; 45.8%) to IV (6/24; 25.0%) on a Merlin scale. In total, 14 of 24 (58.3%) studies were published in a scientific journal ranked in the first quartile of their subject area. The 24 original articles mainly focused on adverse drug reactions already observed during clinical trials (i.e., idiosyncratic systemic reactions). In conclusion, during the last three decades and a burst was not observed in the Italian clinical research investigating contrast-induced nonrenal adverse drug reactions. High-quality clinical research is needed especially for procedures to prevent the onset of the aforementioned events, to identify risk factors, to minimize the risk of their occurrence, and to optimize their related prognosis.
http://www.jpharmacol.com/currentissue.asp?sabs=y

Phosphodiesterase 7B1 as therapeutic target for treatment of cognitive dysfunctions in multiple sclerosis

 p. 126

Arthi Balsundaram, Darling Chellathai
DOI:10.4103/jpp.JPP_77_18  
Multiple sclerosis (MS) is an autoimmune, chronic degenerative neuroinflammatory disorder affecting younger age groups of the United States of America and Europe. MS prevalence studies in India have shown that India is no longer a low-risk zone. Many studies have shown the seriousness of cognitive impairments (CIs) and its types caused in MS. In this review, the pathological basis for CI in various stages of MS was reviewed and revealed to provide a basis for the treatment. Role of phosphodiesterase 7B1 (PDE7B1) inhibitors in treating CI related to MS were also stated in this review. The literature for this review was collected from PubMed and Embase.
http://www.jpharmacol.com/currentissue.asp?sabs=y

Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Response in rheumatoid arthritis

Abstract

The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: − 3.53, minimum: − 6.77; maximum: + 0.48) and CZP 200 mg (median: − 3.13, minimum: − 6.37; maximum: − 0.52) compared to the methotrexate group (median − 2.41, minimum: − 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: − 0.009 g/cm², minimum: − 0.059 g/cm²; maximum: + 0.095 g/cm²) and CZP 400 mg (median: − 0.008 g/cm², minimum: − 0.064 g/cm²; maximum: + 0.080 g/cm²). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: − 0.024 g/cm², minimum: − 0.102 g/cm²; maximum: + 0.057 g/cm²). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.

https://ift.tt/2LpHwX3

Duodenoscope-Associated Infections: Update on an Emerging Problem

Abstract

The duodenoscope is among the most complex medical instruments that undergo disinfection between patients. Transmission of infection by contaminated scopes has remained a challenge since its inception. Notable risk factors for pathogen transmission include non-adherence to disinfection guidelines, encouragement of biofilm deposition due to complex design and surface defects and contaminated automated endoscope reprocessors. The most common infections following endoscopy are endogenous infections involving the patient's own gut flora. Exogenous infections, on the other hand, are associated with contaminated scopes and can theoretically be prevented by effective reprocessing. Pseudomonas aeruginosa is currently the most common organism isolated from contaminated endoscopes. Of note, reports of multidrug-resistant duodenoscopy-associated outbreaks have surfaced recently, many of which occurred despite adequate reprocessing. The FDA and CDC currently recommend comprehensive cleaning followed with at least high-level disinfection for reprocessing of flexible GI endoscopes. Reports of duodenoscope-related outbreaks despite compliance with established guidelines have prompted professional and government bodies to revisit existing guidelines and offer supplementary recommendations for duodenoscope processing. For the purposes of this review, we identified reports of duodenoscope-associated infections from 2000 till date. For each outbreak, we noted the organisms isolated, the number of cases reported, any possible explanations of contamination, and the measures undertaken to end each outbreak. We have also attempted to present an overview of recent developments in this rapidly evolving field.

https://ift.tt/2LnTdgR

Symptomatic psoriatic dactylitis is associated with ultrasound determined extra-synovial inflammatory features and shorter disease duration

Abstract

Objectives

To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis.

Methods

Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment.

Results

The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons).

Conclusions

Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.

https://ift.tt/2R17MfL

A successful report of mitral valve repair for parachute-like mitral valve in adult

Abstract

A 65 year-old man was diagnosed with congestive heart failure secondary to severe mitral regurgitation resulting from a parachute-like asymmetrical mitral valve. We performed mitral annuloplasty and triangular resection of the thick tissue. The postoperative course was uneventful with no recurrence of mitral regurgitation.

https://ift.tt/2S8ZlMH

Focus on current and future management possibilities in inflammatory bowel disease-related chronic pain

Abstract

Introduction

Visceral pain is a symptom reported by over 70% of inflammatory bowel disease (IBD) sufferers. So far, a single, specific cause of this debilitating state has not been established. Chronic pain is one of the most important factors decreasing the quality of life in IBD course. Concurrently, management of pain is the most challenging issue encountered by clinicians in IBD treatment.

Areas covered

This review focuses on pathophysiology of inflammatory bowel disease-caused visceral pain and explores currently available approaches to its management. We also covered recent pharmacological developments in the field.

Conclusions

Pain-related disability has major effects on quality of life and on functional and social outcomes in IBD patients. Currently, there is no one standardized method of managing chronic visceral pain in IBD. Therefore, future development, focusing primarily on alleviating the pain, but also on reducing inflammation, is essential.

https://ift.tt/2GFWCcr

Head-Eye Coordination of Humanoid Robot with Potential Controller

Abstract

With the advancements in the field of anthropomorphic robots, the interest in generating human-like motions has grown ever so rapidly. A major role in this regard is played by control algorithms that produce appropriate dynamic responses with the robot hardware. In this paper we utilized a potential controller to obtain human-like head-eye movements of a robotic android head. The orientations of the robotic head and eyes were subjected to the same constraints that govern human head and eye orientations to the extent allowed by the mechanical design. On top of the potential controller, visual feedback was used to improve the precision of visual target acquisition. The controller was tested in two scenarios; acquiring a fixed target and tracking a moving target in the field of view of the robot. Head orientations of the robot were compared to those of a human subject for a target tracking experiment. Results indicate that the controller is capable of performing object tracking tasks while exhibiting realistic human-like head orientations.

https://ift.tt/2PMcysE

Comparison of two different laser photobiomodulation protocols on the viability of random skin flap in rats

Abstract

To identify the best low level laser photobiomodulation application site at the same irradiation time to increase the viability of the skin flap in rats. Eighteen male rats (Rattus norvegicus: var. Albinus, Rodentia Mammalia) were randomly distributed into three groups (n = 6). Group I (GI) was submitted to simulated laser photobiomodulation; group II (GII) was submitted to laser photobiomodulation at three points in the flap cranial base, and group III (GIII) was submitted to laser photobiomodulation at 12 points distributed along the flap. All groups were irradiated with an Indium, Galium, Aluminum, and Phosphorus diode laser (InGaAlP), 660 nm, with 50 mW power, irradiated for a total time of 240 s in continuous emission mode. The treatment started immediately after performing the cranial base random skin flap (10 × 4 cm² dimension) and reapplied every 24 h, with a total of five applications. The animals were euthanized after the evaluation of the percentage of necrosis area, and the material was collected for histological analysis on the seventh postoperative day. GII animals presented a statistically significant decrease for the necrosis area when compared to the other groups, and a statistically significant increase in the quantification of collagen when compared to the control. We did not observe a statistical difference between the TGFβ and FGF expression in the different groups evaluated. The application of laser photobiomodulation at three points of the flap cranial base was more effective than at 12 points regarding the reduction of necrosis area.

https://ift.tt/2BshX3a

A framework for testing dynamic classification of vulnerable scenarios in ensemble water supply projections

Abstract

Recent water resources planning studies have proposed climate adaptation strategies in which infrastructure and policy actions are triggered by observed thresholds or "signposts." However, the success of such strategies depends on whether thresholds can be accurately linked to future vulnerabilities. This study presents a framework for testing the ability of adaptation thresholds to dynamically identify vulnerable scenarios within ensemble projections. Streamflow projections for 91 river sites predominantly in the western USA are used as a case study in which vulnerability is determined by the ensemble members with the lowest 10% of end-of-century mean annual flow. Illustrative planning thresholds are defined through time for each site based on the mean streamflow below which a specified fraction of scenarios is vulnerable. We perform a leave-one-out cross-validation to compute the frequency of incorrectly identifying or failing to identify a vulnerable scenario (false positives and false negatives, respectively). Results show that in general, this method of defining thresholds can identify vulnerable scenarios with low false positive rates (< 10%), but with false negative rates for many rivers remaining higher than random chance until roughly 2060. This finding highlights the tradeoff between frequently triggering unnecessary action and failing to identify potential vulnerabilities until later in the century, and suggests room for improvement in the threshold-setting technique that could be benchmarked with this approach. This testing framework could extend to thresholds defined with multivariate statistics, or to any application using thresholds and ensemble projections, such as long-term flood and drought risk, or sea level rise.

https://ift.tt/2UVPVpl

Inhibition of Carrageenan/Kaolin-Induced Arthritis in Rats and of Inflammatory Cytokine Expressions in Human IL-1β-Stimulated Fibroblast-like Synoviocytes by a Benzylideneacetophenone Derivative

Abstract

The benzylideneacetophenone derivative JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] (JC3) was synthesized by modifying yakuchinone B obtained from the seeds of Alpinia oxyphylla, a member of the ginger family (Zingiberaceae), which are widely used as a folk remedy and as an anti-inflammatory. The aim of this study was to investigate the anti-arthritic effects of JC3 in rat models of carrageenan-induced paw pain and carrageenan/kaolin-induced knee arthritis. The anti-nociceptive effect of JC3 was assessed by measuring paw withdrawal pressure thresholds using an analgesy-meter. Arthritic symptoms in our monoarthritic rat model were evaluated using weight distribution ratios (WDR), paw thicknesses, and serum prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular endothelial growth factor (VEGF) levels (determined by ELISA). Histological analyses of knee joints were performed after injecting JC3 intraperitoneally into rats before carrageenan treatment at 5 or 10 mg/kg/day for 6 days. The anti-inflammatory effects of JC3 were investigated in vitro using interleukin-1beta (IL-1β)-stimulated fibroblast-like synoviocytes (FLS) derived from arthritis patients. PGE2, IL-6, and IL-8 levels were measured after treating FLS with JC3. In arthritis-induced rats, JC3 treatment significantly decreased nociceptive and arthritic symptoms at days 5 to 6 after carrageenan/kaolin injection. Histological staining of knee tissue showed that JC3 significantly reduced inflammatory areas in the knee joints. Furthermore, JC3 inhibited the expressions of IL-6 and IL-8 in FLS cells at concentrations of 5–10 μg/ml and decreased PGE₂ levels in FLS cells. These findings suggest JC3 has anti-arthritic effects in in vivo and in vitro, and that it might be useful for the treatment of arthritis.

https://ift.tt/2RbZsKh

The Value of Treatment Processes in Germany: A Discrete Choice Experiment on Patient Preferences in Complementary and Conventional Medicine

Abstract

Background

The effects of health interventions are often complex, and it is argued that they comprise more than pure changes in clinical parameters. Aspects of the treatment process, so-called 'benefits beyond health', are often overlooked in the evaluation of health interventions but can be of value to the patients.

Objectives

The aim of this study was to assess patients' preferences and willingness to pay regarding the treatment process and its attributes in patients using acupuncture, homeopathy or general medicine (GM).

Methods

A systematic literature search, six semi-structured interviews and a stakeholder involvement were conducted to determine the attributes of the treatment process. Five process attributes and one cost attribute were used to construct the experimental design of the discrete choice experiment (DCE) (6 × 3), a cross sectional survey method. Patients were recruited by outpatient physicians practicing in Berlin and Munich, Germany. Process attributes were effects-coded. Data were analyzed in a conditional logit regression.

Results

Data from 263 patients were analyzed. DCE results showed that the treatment process attributes 'active listening' and 'time' were most relevant to all patients. Preferences for the attributes 'holistic treatment' (more relevant to the acupuncture and homeopathy groups) and 'information' (more relevant to the GM group) seemed to differ slightly between the groups. Willingness-to-pay values were higher in the acupuncture and homeopathy groups.

Conclusions

The time physicians take and the extent to which they listen attentively are most important and are equally important to all patients. These results may contribute to the debate about more patient-centered healthcare. They support a strengthening of medical consultations in the German healthcare system. We suggest giving physicians the opportunity to spend more time with their patients, which may be achieved by changing the general conditions of remuneration (e.g., improved reimbursement of medical consultations).

German Clinical Trial Register

DRKS00013160.

https://ift.tt/2GokW26

Cortical degeneration in chronic traumatic encephalopathy and Alzheimer’s disease neuropathologic change

Abstract

Objectives

An observational study to compare the laminar distributions in frontal and temporal cortex of the tau-immunoreactive pathologies in chronic traumatic encephalopathy (CTE) and Alzheimer's disease neuropathologic change (ADNC).

Patients

Post-mortem material of (1) four cases of CTE without ADNC, (2) seven cases of CTE with ADNC (CTE/ADNC), and (3) seven cases of ADNC alone.

Results

In CTE and CTE/ADNC, neurofibrillary tangles (NFT), neuropil threads (NT), and dot-like grains (DLG) were distributed either in upper cortex or across all layers. Low densities of astrocytic tangles (AT) and abnormally enlarged neurons (EN) were not localized to any specific layer. Surviving neurons exhibited peaks of density in both upper and lower cortex, and vacuole density was greatest in superficial layers. In ADNC, neuritic plaques (NP) were more frequent, AT rare, NFT and NT were more widely distributed, NT affected lower layers more frequently, and surviving neurons were less frequently bimodal than in CTE and CTE/ADNC.

Conclusion

Tau pathology in CTE and CTE/ADNC consistently affected the upper cortex but was more widely distributed in ADNC. The presence of CTE may encourage the development of ADNC pathology later in the course of the disease.

https://ift.tt/2PMehOw

Analysis of spinal and muscle pathology in transgenic mice overexpressing wild-type and ALS-linked mutant MATR3

Abstract

Mutations in MATR3 have been associated with amyotrophic lateral sclerosis (ALS) as well as a form of distal myopathy termed vocal cord pharyngeal distal myopathy (VCPDM). To begin to understand how mutations in MATR3 may cause disease, here we provide initial characterization of transgenic (Tg) mice expressing human wild-type (WT) MATR3 (MATR3^WT) and ALS-mutant F115C MATR3 (MATR3^F115C) proteins under the control of the mouse prion promoter (MoPrP). For each construct, we established multiple independent lines of mice that stably transmitted the transgene. Unexpectedly, for all stably-transmitting lines examined, MATR3 transgenic mRNA expression was more robust in muscle, with minimal expression in spinal cord. The levels of transgenic mRNA in muscle did not differ between mice from our lead MATR3^F115C line and lead MATR3^WT line, but mice from the lead MATR3^F115C line had significantly higher levels of MATR3 protein in muscle over the lead MATR3^WT line. Mice from the three independent, established lines of MATR3^F115C mice developed weakness in both fore- and hind-limbs as early as < 1 months of age; whereas, MATR3^WT mice aged to > 20 months were not overtly distinguishable from non-transgenic (NT) littermates based on basic motor phenotype. Muscle of both MATR3^WT and MATR3^F115C mice showed vacuoles by 2 months of age which worsened by ~ 10 months, but vacuolation was noticeably more severe in MATR3^F115C mice. Overall, our results indicate that increasing the levels of MATR3 in muscle can cause pathologic changes associated with myopathy, with MATR3^F115C expression causing overt muscle atrophy and a profound motor phenotype. The findings suggest that analysis of muscle pathology in individuals harboring ALS-linked MATR3 mutations should be routinely considered.

https://ift.tt/2V1OfuO

Molecular analysis of cox-1 and 18S rRNA gene fragments of Eimeria species isolated from endangered grouse: capercaillie ( Tetrao urogallus ) and black grouse ( Tetrao tetrix )

Abstract

This paper is the first record describing the molecular analysis of Eimeria species occurring in capercaillie (Tetrao urogallus) and black grouse (Tetrao tetrix) which inhabit northern Eurasia and are species critically endangered of extinction. Actions undertaken to protect endangered species, such as breeding individuals in closed aviaries, could allow saving those birds, but they also pose risk of accidental healing of invasive diseases, like coccidiosis. Therefore, an investigation was conducted on fecal samples collected from the capercaillies and black grouse originating from the Kirov region (Russia) and breeding centers located in Poland. Results indicate that the average prevalence of Eimeria revealed 72% (average OPG = 3548) and 80% (average OPG = 5220) in capercaillies and black grouse respectively. Most of the Eimeria spp. oocysts were non-sporulated; however, two different morphological types were observed. The phylogenetic analysis of cox-1 and 18S rRNA genes revealed the analyzed Eimeria sequences to belong to two species. In addition, it showed some similarities between both analyzed genes. Most of the sequences obtained from both grouse species coccidia belonged to one species partially homologous to the Eimeria spp. isolated from ring-necked pheasant (approx. 94 and 96% for cox-1 and 18S rRNA genes, respectively). Two strains isolated from capercaillies imported from Russia were related to turkey coccidia: E. innocua and E. dispersa (97–99% homology) in the cox-1 gene analysis and only one of them was related to those Eimeria species in the 18S rRNA gene analysis (98–99% homology).

https://ift.tt/2EsqYMK

Relative Value of Adapted Novel Bibliometrics in Evaluating Surgical Academic Impact and Reach

Abstract

Background

The Hirsch index, often used to assess research impact, suffers from questionable validity within the context of General Surgery, and consequently adapted bibliometrics and altmetrics have emerged, including the r-index, m-index, g-index and i10-index. This study aimed to assess the relative value of these novel bibliometrics in a single UK Deanery General Surgical Consultant cohort.

Method

Five indices (h, r, m, g and i10) and altmetric scores (AS) were calculated for 151 general surgical consultants in a UK Deanery. Indices and AS were calculated from publication data via the Scopus search engine with assessment of construct validity and reliability.

Results

The median number of publications, h-index, r-index, m-index, g-index and i10-index were 13 (range 0–389), 5 (range 0–63), 5.2 (range 0–64.8), 0.33 (range 0–1.5), 10 (range 0–125) and 4 (range 0–245), respectively. Correlation coefficients of r-index, m-index, g-index and i10-index with h-index were 0.913 (p < 0.001), 0.716 (p < 0.001), 0.961 (p < 0.001) and 0.939 (p < 0.001), respectively. Significant variance was observed when the cohort was ranked by individual bibliometric measures; the median ranking shifts were: r-index − 2 (− 46 to + 23); m-index − 6.5 (− 53 to + 22); g-index − 0.5 (− 24 to + 13); and i10-index 0 (− 8 to + 11), respectively (p < 0.001). The median altmetric score and AS index were 0 (range 0–225.5) and 1 (range 0–10), respectively; AS index correlated strongly with h-index (correlation coefficient 0.390, p < 0.001).

Conclusions

Adapted bibliometric indices appear to be equally valid measures of evaluating academic productivity, impact and reach.

https://ift.tt/2GtO20h

Nonlinear auditory models yield new insights into representations of vowels

Abstract

Studies of vowel systems regularly appeal to the need to understand how the auditory system encodes and processes the information in the acoustic signal. The goal of this study is to present computational models to address this need, and to use the models to illustrate responses to vowels at two levels of the auditory pathway. Many of the models previously used to study auditory representations of speech are based on linear filter banks simulating the tuning of the inner ear. These models do not incorporate key nonlinear response properties of the inner ear that influence responses at conversational-speech sound levels. These nonlinear properties shape neural representations in ways that are important for understanding responses in the central nervous system. The model for auditory-nerve (AN) fibers used here incorporates realistic nonlinear properties associated with the basilar membrane, inner hair cells (IHCs), and the IHC-AN synapse. These nonlinearities set up profiles of f0-related fluctuations that vary in amplitude across the population of frequency-tuned AN fibers. Amplitude fluctuations in AN responses are smallest near formant peaks and largest at frequencies between formants. These f0-related fluctuations strongly excite or suppress neurons in the auditory midbrain, the first level of the auditory pathway where tuning for low-frequency fluctuations in sounds occurs. Formant-related amplitude fluctuations provide representations of the vowel spectrum in discharge rates of midbrain neurons. These representations in the midbrain are robust across a wide range of sound levels, including the entire range of conversational-speech levels, and in the presence of realistic background noise levels.

https://ift.tt/2rLYA0w

The Hybrid Electronic Medical Registry Allows Benchmarking of Quality of Trauma Care: A Five-Year Temporal Overview of the Trauma Burden at a Major Trauma Centre in South Africa

Abstract

Introduction

This study is a five-year follow-up of previously published review of the trauma workload at our institution. It aims to provide evidence about the quality of trauma care delivered by a major academic trauma service in South Africa to provide a temporal analysis of trauma trends in the city of Pietermaritzburg.

Materials and methods

All trauma patients admitted by the Pietermaritzburg Metropolitan Trauma Service (PMTS) for the period December 2012-April 2018 were retrieved from the Hybrid Electronic Medical Registry (HEMR) for analysis.

Results

Over the five-year period, a total of 8722 trauma patients were admitted to Grey's Hospital. There were 7242 (83.0%) males. The average age was 29.66 years. A total of 1719 (19.7%) patients less than 19 years of age, 377 (4.3%) older than 60 years of age and 1480 (17.0%) female patients were admitted following trauma. Table 3 breaks down the mechanism of trauma. A total of 5027 patients sustained blunt trauma (57.6%), and 3334 (38.5%) sustained penetrating trauma. A total of 4808 patients sustained intentional trauma implying that 55.1% of all trauma was secondary to grievous bodily harm or assault either in the form of a stab wound or GSW or of an assault. There was a total of 2232 road traffic-related incidents, of which 37.9% (845) were pedestrian victims. The mortality rate for all trauma admissions was 4.5% (396). Of these 396 deaths, 64 (16.2%) were classified at the morbidity and mortality conference as being avoidable.

Conclusions

The HEMR has allowed us to track the burden of trauma presenting to our institution over a five-year period. This confirms previous studies over shorter time periods from our institution. The pattern of trauma has remained consistent, and the previously described high levels show no sign of decreasing. Interventions to try and reduce this burden are urgently required.

https://ift.tt/2R65njI

Cross-Ring Fragmentation Patterns in the Tandem Mass Spectra of Underivatized Sialylated Oligosaccharides and Their Special Suitability for Spectrum Library Searching

Abstract

Reference spectral library searching, while widely used to identify compounds in other areas of mass spectrometry, is not commonly used in glycomics. Building on a study by Cotter and coworkers on analysis of sialylated oligosaccharides using atmospheric pressure-matrix-assisted laser-induced tandem mass spectrometry (MS/MS), we show that library search methods enable the automated differentiation of such sialylated oligosaccharide isomers using MS/MS derived from electrospray collision-induced dissociation in ion trap and beam-type fragmentation mass spectrometers. We compare MS/MS spectra of five sets of native sialylated oligosaccharide isomers and show a spectral library search method that can distinguish between these isomers using the precursor ion [M+2X-H]⁺, where X=Li, Na, or K. Sialic acid linkage (α2,3 vs. α2,6) is known to have a dramatic effect on the fragmentation of the sialylated compounds. We found that ^2,4A3 cross-ring fragment at the terminal monosaccharide in sialyllactoses, sialyllactosamines, and sialyl pentasaccharides is highly abundant in the MS/MS spectra of [M+2X-H]⁺ species of α2,6-NeuAc glycans, while (^2,4A3-H2O) fragment is highly abundant in α2,3-NeuAc moiety. The ^2,4A3-H2O peak is specific to NeuAc-α2,3-Gal-β1,4-Y (Y=GlcNAc or Glc). To our knowledge, this observation was not reported previously. Theoretical calculations reveal major conformational differences between α2,6-NeuAc and α2,3-NeuAc structures that provide reasonable explanations for the observed fragmentation patterns. Other singly-charged ions ([M+X]⁺) do not show similar cross-ring cleavages. Implemented in a searchable library, these spectral differences provide a facile method to distinguish sialyl isomers without derivatization. We also found good spectral matching across instruments. MS/MS spectra and tools are available at http://chemdata.nist.gov/glycan/spectra.

Graphical Abstract

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https://ift.tt/2Lt4xZm

Idiopathic intracranial hypertension in the British population with obesity

Abstract

Purpose

Idiopathic intracranial hypertension (IIH) is a syndrome that is characterized by persistently high intracranial pressure and associated with high rates of morbidity and visual loss. Its exact etiology and clinical picture is poorly understood, but it is known to be associated with obesity. The aim of this study was to investigate the prevalence and clinical manifestations of IIH using a large nationwide database of British subjects.

Materials and methods

The anonymized healthcare records of patients with a BMI of ≥ 30 kg/m² were extracted from the Clinical Practice Research Datalink (CPRD), and analyzed.

Results

The patients with IIH were older and more likely to have peripheral vascular disease, ischemic heart disease, and anemia; to have had a previous myocardial infarction; and have used non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. Multivariate analysis with adjustment for confounders showed that anemia (p = 0.033) and the use of NSAIDs (p = 0.011) were the only factors independently associated with IIH. Increases in BMI beyond the threshold of obesity did not independently increase risk of IIH.

Conclusions

IIH is a multifactorial disease; the risk of which is increased in patients with a background of anemia, and those who use NSAIDs. Across BMI categories beyond the threshold for obesity (BMI ≥ 30 kg/m²), there is no continuation of the previously described "dose-response" relationship between BMI and IIH.

Ethical approval

Scientific approval for the study was granted from the Regulatory Agency's Independent Scientific Advisory Committee and ethical approval by the Health Research Authority IRAS Project ID: 203143. ISAC approval registration number 16_140R2.

https://ift.tt/2EAIIGD

Taeniectomy Versus Transverse Coloplasty as Neorectum After Low Rectal Resection

Abstract

Purpose

Restorative surgery for rectal cancer is usually criticized by its functional outcomes. The aim of this study is to assess the efficacy "taeniectomy" pouch in comparison with transverse coloplasty pouch.

Study design

This was a prospective controlled study. Most patients who were candidate for low rectal resection presented to colorectal unit at Cairo university hospitals during the period from February 2013 to August 2016 were divided into two groups. The total number of patients enrolled in the study was 180 patients. Ninety patients were subjected to low rectal resection with the transverse coloplasty pouch, and 90 patients were subjected to low rectal resection with the newly described taeniectomy pouch. Safety and feasibility of both techniques were assessed about leakage, operative time, difficulty in evacuation, incontinence, number of daily motions and postoperative urgency. Both groups were assessed clinically, by means of defecography and anorectal manometry.

Results

There was no significant statistical difference between taeniectomy and transverse coloplasty regarding postoperative leakage (P value = 0.988), postoperative mortality (P value = 0.99) and functional outcomes including number of motions per day (P value was 0.403 at 3 months and 0.361 at 12 months), urgency (P value was 0.688), continence grade (P value was 0.320 and 0.683 in 3 and 12 months, respectively) and manometric findings. However, taeniectomy is statistically significant better in terms of operative time (P value = 0.001).

Conclusions

Taeniectomy is a newly described, technically easier technique for pouch formation after low rectal resection that can be used as a safe and effective alternative for the widely used transverse coloplasty.

https://ift.tt/2S8p4Vx

Understanding Disparities in Surgical Outcomes for Medicaid Beneficiaries

Abstract

Background

Few studies have evaluated whether outcome disparities between Medicaid and private insurance beneficiaries are driven by the hospital at which the patient receives care. The purpose of this study was to evaluate the effect of the hospital on surgical outcomes in Medicaid beneficiaries.

Methods

We identified 139,566 non-elderly Medicaid and private insurance beneficiaries undergoing general, vascular, or gynecological surgery between 2012 and 2017 using a statewide clinical registry in Michigan. We calculated risk-adjusted rates of complications, readmissions, emergency department (ED) visits, and post-acute care utilization using multivariable logistic regression, accounting for patient and procedural factors. We then evaluated whether, and to what extent, the hospital influenced outcome disparities between Medicaid and privately insured beneficiaries.

Results

Risk-adjusted rates for all outcomes were higher in Medicaid beneficiaries. For example, overall post-discharge ED visit rates were 14.3% (95% CI 13.7% to 14.9%) for Medicaid compared to 7.5% (95% CI 7.1% to 7.9%, P < 0.01) for private insurance beneficiaries. Hospital factors explained 3.9% of the observed difference in complication rates between Medicaid and private insurance beneficiaries. In contrast, hospital factors explained a greater proportion of the disparities in readmissions (30.6%), ED visits (33.0%), and post-acute care utilization (16.1%). Results were similar when restricting the study population to elective cases only.

Conclusions

Hospital factors account for a significant proportion of the disparities in post-discharge resource utilization between Medicaid and private insurance beneficiaries. Policies aiming to improve the quality and equity of surgical care for Medicaid beneficiaries should focus on the post-discharge period.

https://ift.tt/2A38jnK

Pure Laparoscopic Right Posterior Sectionectomy Using the Glissonean Approach and a Modified Liver Hanging Maneuver (Video)

Abstract

Background

Laparoscopic right posterior sectionectomy is technically challenging secondary to poor exposure of the surgical field and difficulty with controlling hemorrhage during deeper parenchymal transection Cho et al., Surgery 158:135–141, 2015; Lee et al., Surgery 160:1219–1226, 2016. We present laparoscopic right posterior sectionectomy using the Glissonean approach and a modified liver hanging maneuver.

Methods

A 57-year-old man presented with a single mass in segment 7 of the liver. He was placed in the lithotomy position, and five trocars were used in the upper abdomen. The hepatoduodenal ligament was encircled using an umbilical tape to perform the intermittent Pringle maneuver.

After detachment of the hilar plate, the right posterior Glissonean pedicle was dissected and clamped to confirm ischemic delineation Takasaki, J Hepato-Biliary-Pancreat Surg 5:286–291, 1998. After complete mobilization of the right liver, the hanging tape was placed along the inferior vena cava between the caval ligament and the right hepatic vein. The hanging tape elevates the liver and guides the surgeon to achieve an accurate transection plane

Belghiti et al., J Am Coll Surg 193:109–111, 2001; Kim et al., Surg Endosc 30:3611–3617, 2016; Kim, Choi, J Gastrointest Surg 21:1181–1185, 2017; Kim et al., Langenbecks Arch Surg 403:131–135, 2018 . The transection plane used during a right posterior sectionectomy is horizontal and follows the inferior vena cava. However, with the liver hanging maneuver, the horizontal transection plane becomes vertical.

Result

The operation time was 290 min, the estimated blood loss was 120 mL, and the total Pringle maneuver time was 60 min. Final histopathological diagnosis showed a 1.7-cm-sized hepatocellular carcinoma with the resection margin measuring 1.5 cm. The patient was discharged on postoperative day 7 without any complications.

Conclusion

A Glissonean approach with a modified liver hanging maneuver is feasible and useful for laparoscopic right posterior sectionectomy.

https://ift.tt/2PL17Bx

Periampullary Gangliocytic Paraganglioma

Abstract

Background

Gangliocytic paraganglioma (GP) is rare and difficult to be differentiated from other periampullary neoplasms. The clinical characteristics and optimal treatment of periampullary GPs have not been clarified.

Methods

The data pool for the analysis comprised of cases of periampullary GP encountered in our institution and sporadic cases reported in the English literature.

Results

A total of 117 cases with periampullary GP were studied, including 2 from our institute, and among them, duodenal GP was the most common (53.0%). GP size ranged from 0.7 to 19.0 cm, with a median of 2.2 cm. The most common presenting symptom for overall periampullary GPs was epigastric pain in 49.5% cases, followed by gastrointestinal bleeding in 35.4% cases. Most (84.1%) of the periampullary GPs were benign, whereas 15.9% were malignant. Metastasis was noted in 26.3% of periampullary GPs, with 14.5% showing lymph node metastasis and 1.8% showing liver metastasis. Of the periampullary GP cases included, 30.1% were treated with pancreaticoduodenectomy, 40.6% with local excision, and 17.7% with endoscopic resection.

Conclusions

Periampullary GP should be considered as a tumor with malignant potential. Endoscopic resection is the treatment of choice for most of the duodenal GPs, whereas pancreaticoduodenectomy is recommended for GPs with possible malignancy, such as large size, with submucosal invasion, or pancreatic GP.

https://ift.tt/2UXReED

Idiopathic Rectal Ulcer Associated with Human Immunodeficiency Virus Infection

https://ift.tt/2UOUZvX

The Influence of Age on Complications and Overall Survival After Ivor Lewis Totally Minimally Invasive Esophagectomy

Abstract

Background

The number of elderly patients suffering from esophageal cancer is increasing, due to an increasing incidence of esophageal cancer and increasing life expectancy. However, the effect of age on morbidity, mortality, and survival after Ivor Lewis total minimally invasive esophagectomy (TMIE) is not well known.

Methods

A prospectively documented database from December 2010 to June 2017 was analyzed, including all patients who underwent Ivor Lewis TMIE for esophageal cancer in three Dutch high-volume esophageal cancer centers. Patients younger than 75 years (younger group) were compared to patients aged 75 years or older (elderly group). Baseline patient characteristics and perioperative data were included. Surgical complications were graded using the Clavien-Dindo scale. The primary outcome was postoperative complications Clavien-Dindo ≥ 3. Secondary outcome parameters were postoperative complications, in-hospital mortality, 30- and 90-day mortality and survival.

Results

Four hundred and forty-six patients were included, 357 in the younger and 89 in the elderly group. No significant differences were recorded regarding baseline patient characteristics. There was no significant difference in complications graded Clavien-Dindo ≥ 3 and overall complications, short-term mortality, and survival. Delirium occurred in 27.0% in the elderly and 11.8% in the younger group (p < 0.001). After correction for baseline comorbidity this difference remained significant (p = 0.001). Median hospital length of stay was 13 days in the elderly and 11 days in the younger group (p = 0.010).

Conclusions

Ivor Lewis TMIE can be safely performed in selected elderly patients without increasing postoperative morbidity and mortality.

https://ift.tt/2PKl0sp

Gastric Synovial Sarcoma

https://ift.tt/2UTQ6BS

A New Model for Congenital Vestibular Disorders

Abstract

Many developmental disorders of the inner ear are manifested clinically as delayed motor development and challenges in maintaining posture and balance, indicating involvement of central vestibular circuits. How the vestibular circuitry is rewired in pediatric cases is poorly understood due to lack of a suitable animal model. Based on this, our lab designed and validated a chick embryo model to study vestibular development in congenital vestibular disorders. The developing inner ear or "otocyst" on the right side of 2-day-old chick embryos (E2) was surgically rotated 180° in the anterior–posterior axis, forming the "anterior–posterior axis rotated otocyst chick" or ARO chick. The ARO chick has a reproducible pathology of a sac with truncated or missing semicircular canals. A sac is the most common inner ear defect found in children with congenital vestibular disorders. In E13 ARO chicks, the sac contained all three cristae and maculae utriculi and sacculi, but the superior crista and macula utriculi were shortened in anterior–posterior extent. Also, the number of principal cells of the tangential vestibular nucleus, a major avian vestibular nucleus, was decreased 66 % on the rotated side. After hatching, no difference was detected between ARO and normal chicks in their righting reflex times. However, unlike normal chicks, ARO hatchlings had a constant, right head tilt, and after performing the righting reflex, ARO chicks stumbled and walked with a widened base. Identifying the structure and function of abnormally developed brain regions in ARO chicks may assist in improving treatments for patients with congenital vestibular disorder.

https://ift.tt/2QZyJjV

Removal of Agrichemicals from Water Using Granular Activated Carbon Filtration

Abstract

The objective was to evaluate removal efficacy of agrichemicals from water using a small-scale granular activated carbon (GAC) system. The GAC system consisted of a series of three 1.9- to 4.1-L filter canisters filled with 8 × 30 US mesh (595 to 2380 μm) bituminous coal GAC. In experiment 1, 11 agrichemicals (acephate, bifenthrin, chlorpyrifos, flurprimidol, glyphosate, hydrogen peroxide + peracetic acid, imidacloprid, paclobutrazol, didecyldimethylammonium chloride (DDAC), triclopyr, and uniconazole) used in greenhouse and nursery production were exposed to 0, 12, or 64 s of GAC contact time. Chemical concentrations were prepared at a 1:10 dilution of a recommended label rate for ornamental crops to represent a possible residual concentration found in recaptured irrigation or surface water. In experiment 2, three other chemicals [iron ethylene diamine-N,N′-bis(hydroxy phenyl acetic acid) (iron-EDDHA, a chelated iron fertilizer), soracid blue dye (a fertilizer dye), and sodium hypochlorite (a sanitizing agent)] were also tested with 0, 12, 38, or 64 s of GAC contact time. Agrichemical concentration was reduced with 12 s of GAC contact time compared with the 0 s for all chemicals tested, and in most cases was further increased at 64-s contact time. Chemicals reduced below their minimum detection limits with 64 s GAC included acephate, flurprimidol, paclobutrazol, uniconazole, peracetic acid, DDAC, and chlorine (free and total). Percent reduction for other chemicals with 64 s GAC was 72.2% for bifenthrin, 89% chlorphyrifos, 85.3% imidacloprid, 99% glyphosate, 99.4% triclopyr, 99.3% hydrogen peroxide, 47.6% iron-EDDHA, and 94.6% soracid blue dye. Iron-EDDHA and soracid blue dye could be used as indicator chemicals for onsite monitoring of GAC filter efficacy. Results indicate that GAC filtration can remove a wide range of agrichemical contaminants commonly used in greenhouse and nursery production, although the required contact time in commercial production is expected to be greater than in this research study.

https://ift.tt/2BqQtLb

Degradative enzymes for type II arabinogalactan side chains in Bifidobacterium longum subsp. longum

Abstract

Type II arabinogalactan (AG) is a soluble prebiotic fiber stimulating the proliferation of bifidobacteria in the human gut. Larch AG, which is comprised of type II AG, is known to be utilized as an energy source for Bifidobacterium longum subsp. longum (B. longum). We have previously characterized GH43_24 exo-β-1,3-galactanase (Bl1,3Gal) for the degradation of type II AG main chains in B. longum JCM1217. In this study, we characterized GH30_5 exo-β-1,6-galactobiohydrolase (Bl1,6Gal) and GH43_22 α-l-arabinofuranosidase (BlArafA), which are degradative enzymes for type II AG side chains in cooperation with exo-β-1,3-galactanase. The recombinant exo-β-1,6-galactobiohydrolase specifically released β-1,6-galactobiose (β-1,6-Gal₂) from the nonreducing terminal of β-1,6-galactooligosaccharides, and the recombinant α-l-arabinofuranosidase released arabinofuranose (Araf) from α-1,3-Araf-substituted β-1,6-galactooligosaccharides. β-1,6-Gal₂ was additively released from larch AG by the combined use of type II AG degradative enzymes, including Bl1,3Gal, Bl1,6Gal, and BlArafA. The gene cluster encoding the type II AG degradative enzymes is conserved in all B. longum strains, but not in other bifidobacterial species. The degradative enzymes for type II AG side chains are thought to be important for the acquisition of type II AG in B. longum.

https://ift.tt/2SQNVx0

Metabolic engineering of Corynebacterium glutamicum for l -cysteine production

Abstract

l-cysteine, a valuable sulfur-containing amino acid, has been widely used in food, agriculture, and pharmaceutical industries. Due to the toxicity and complex regulation of l-cysteine, no efficient cell factory has yet been achieved for l-cysteine industrial production. In this study, the food-grade microorganism Corynebacterium glutamicum was engineered for l-cysteine production. Through deletion of the l-cysteine desulfhydrases (CD) and overexpression of the native serine acetyltransferase (CysE), the initial l-cysteine-producing strain CYS-2 was constructed to produce 58.2 ± 5.1 mg/L of l-cysteine. Subsequently, several metabolic engineering strategies were performed to further promote l-cysteine biosynthesis, including using strong promoter tac-M to enhance expression intensity of CysE, investigating the best candidate among several heterogeneous feedback-insensitive CysEs for l-cysteine biosynthesis, overexpressing l-cysteine synthase (CysK) to drive more metabolic flux, evaluating the efflux capacity of several heterogeneous l-cysteine transporters, engineering l-serine biosynthesis module to increase the precursor l-serine level and using thiosulfate as the sulfur source. Finally, the l-cysteine concentration of the engineered strain CYS-19 could produce 947.9 ± 46.5 mg/L with addition of 6 g/L Na₂S₂O₃, approximately 14.1-fold higher than that of the initial strain CYS-2, which was the highest titer of l-cysteine ever reported in C. glutamicum. These results indicated that C. glutamicum was a promising platform for l-cysteine production.

https://ift.tt/2CkkpKx

A Kinetic Study on the Evolution of Martensitic Transformation Behavior and Microstructures in Ti–Ta High-Temperature Shape-Memory Alloys During Aging

Abstract

Ti–Ta alloys represent candidate materials for high-temperature shape-memory alloys (HTSMAs). They outperform several other types of HTSMAs in terms of cost, ductility, and cold workability. However, Ti–Ta alloys are characterized by a relatively fast microstructural degradation during exposure to elevated temperatures, which gives rise to functional fatigue. In the present study, we investigate how isothermal aging affects the martensitic transformation behavior and microstructures in Ti₇₀Ta₃₀ HTSMAs. Ti–Ta sheets with fully recrystallized grain structures were obtained from a processing route involving arc melting, heat treatments, and rolling. The final Ti–Ta sheets were subjected to an extensive aging heat treatment program. Differential scanning calorimetry and various microstructural characterization techniques such as scanning electron microscopy, transmission electron microscopy, conventional X-ray, and synchrotron diffraction were used for the characterization of resulting material states. We identify different types of microstructural evolution processes and their effects on the martensitic and reverse transformation. Based on these results, an isothermal time temperature transformation (TTT) diagram for Ti₇₀Ta₃₀ was established. This TTT plot rationalizes the dominating microstructural evolution processes and related kinetics. In the present work, we also discuss possible options to slow down microstructural and functional degradation in Ti–Ta HTSMAs.

https://ift.tt/2UXOl6L

Tumor Ablation Enhancement by Combining Radiofrequency Ablation and Irreversible Electroporation: An In Vitro 3D Tumor Study

Abstract

We hypothesized and demonstrated for the first time that significant tumor ablation enhancement can be achieved by combining radiofrequency ablation (RFA) and irreversible electroporation (IRE) using a 3D cervical cancer cell model. Three RFA (43, 50, and 60 °C for 2 min) and IRE protocols (350, 700, and 1050 V/cm) were used to study the combining effect in the 3D tumor cell model. The in vitro experiment showed that both RFA enhanced IRE and IRE enhanced RFA can lead to a significant increase in the size of the ablation zone compared to IRE and RFA alone. It was also noted that the sequence of applying ablation energy (RFA → RE or IRE → RFA) affected the efficacy of tumor ablation enhancement. The electrical conductivity of 3D tumor was found to be increased after preliminary RFA or IRE treatment. This increase in tumor conductivity may explain the enhancement of tumor ablation. Another explanation might be that there is repeat injury to the transitional zone of the first treatment by the second one. The promising results achieved in the study can provide us useful clues about the treatment of large tumors abutting large vessels or bile ducts.

https://ift.tt/2ECcV7Y

Stapler-Less Robotic Partial Gastrectomy: a Safety and Feasibility Experimental Study

Abstract

Background

No true preliminary work has been performed and published on the use of the bipolar cautery devices for transection of the stomach when performed as a part of the sleeve gastrectomy or gastric wedge resection. The objective of this study was to investigate the feasibility and safety of substitution of linear surgical stapling devices for use of a bipolar electrosurgical sealing instrument in the performance of a totally robotic partial gastrectomy (TRPG).

Methods

Ten female pigs were assigned to an intervention or control group. Intervention included TRPG with a robotic bipolar tissue coagulation device. In the control group, TRPG was performed using the staplers. Assessed outcomes included presence of the intraoperative and postoperative bleeding or leak and features of the sections from the stapled line or sutured line.

Results

Mean operating time was (130 ± 31 min) and (87 ± 23 min) in the study and control groups (p = 0.03). Intraoperative gastroscopy revealed slow bleeding associated with the staple line in 3/5 control pigs; oozing was not appreciated in any of the study pigs (0/5). No leak was detected during intraoperative gastroscopy. No major complications were suspected postoperatively or identified at postmortem exam in either group. Mean injury width was (1.12 ± 0.93 mm) in the control group with greater mean injury width (7.88 ± 3.73 mm) in the study group (p = 0.001). Mean depth of ulceration was (0.99 ± 0.94 mm) in the control group, with greater mean ulceration depth (2.25 ± 0.84 mm) in the study group (p = 0.002).

Conclusion

The study showed the technical feasibility of performing stapler-less gastric wedge resection. The electrocautery alone failed to demonstrate the technical feasibility which was obtained with the concomitant use of a tissue clamp and a suture.

https://ift.tt/2rIfQUc

Reply to Gagner’s Letter RE Features of MGB and OAGB

https://ift.tt/2Low51J

The Foundation of the Future of MCH

Abstract

The accompanying article on the Future of Public Health is a timely call to action. It reminds us of our strong roots and also compels us to consider larger societal issues in pursuing our shared goals.

https://ift.tt/2UQoFsu

Interactive effects of linguistic abstraction and stimulus statistics in the online modulation of neural speech encoding

Abstract

Speech processing is highly modulated by context. Prior studies examining frequency-following responses (FFRs), an electrophysiological 'neurophonic' potential that faithfully reflects phase-locked activity from neural ensembles within the auditory network, have demonstrated that stimulus context modulates the integrity of speech encoding. The extent to which context-dependent encoding reflects general auditory properties or interactivities between statistical and higher-level linguistic processes remains unexplored. Our study examined whether speech encoding, as reflected by FFRs, is modulated by abstract phonological relationships between a stimulus and surrounding contexts. FFRs were elicited to a Mandarin rising-tone syllable (/ji-TR/, 'second') randomly presented with other syllables in three contexts from 17 native listeners. In a contrastive context, /ji-TR/ occurred with meaning-contrastive high-level-tone syllables (/ji-H/, 'one'). In an allotone context, TR occurred with dipping-tone syllables /ji-D/, a non-meaning-contrastive variant of /ji-TR/. In a repetitive context, the same /ji-TR/ occurred with other speech tokens of /ji-TR/. Consistent with prior work, neural tracking of /ji-TR/ pitch contour was more faithful in the repetitive condition wherein /ji-TR/ occurred more predictably (p = 1) than in the contrastive condition (p = 0.34). Crucially, in the allotone context, neural tracking of /ji-TR/ was more accurate relative to the contrastive context, despite both having an identical transitional probability (p = 0.34). Mechanistically, the non-meaning-contrastive relationship may have augmented the probability to /ji-TR/ occurrence in the allotone context. Results indicate online interactions between bottom-up and top-down mechanisms, which facilitate speech perception. Such interactivities may predictively fine-tune incoming speech encoding using linguistic and statistical information from prior context.

https://ift.tt/2GvheDV

Interobserver agreement using Schlapbach graded scale for diffuse idiopathic skeletal hyperostosis (DISH): can we reduce the cut-off point of vertebral affection?

Abstract

Resnick-Niwayama criteria for diagnosing DISH depict an advanced stage, and a new reduced cut-off point with three contiguous vertebrae affected (two bone bridges) has been proposed. The aim has been to know the interobserver agreement by using a graded scale of DISH in which grade II matches with the new proposed cut-off point and grade III matches with the first criterion of Resnick-Niwayama. Males ≥ 50 years and postmenopausal women included in a population-based prospective study (the Camargo Cohort) were analyzed. Sample size was obtained according to an expected kappa of 0.95 and an accuracy of ± 8%. Three physicians applied independently Schlapbach graded scale (ranged from grade 0, no ossification, to grade III, ≥ 3 consecutive bone bridges) on the lateral radiographs of thoracic and lumbar spine of participants. We calculated inter- and intra-observer agreement and correlation. One hundred and fifty eight radiographs (79 patients, 68 ± 9 years) were assessed. Kappa values (95% confidence interval) for grades 0, I, II, and III were 0.63 (0.50–0.77), 0.49 (0.37–0.62), 0.32 (0.17–0.47), and 0.69 (0.60–0.77), respectively. Weighted kappa for the three pairs of raters were 0.87 (0.82–0.93), 0.84 (0.77–0.91), and 0.81 (0.72–0.90). Grade III was the image that generated greater agreement, while a significant decrease was noted in grade II, the new proposed criterion. The simultaneous presence of an incomplete DISH and osteoarthritis, in a thoracic spinal segment with peculiar anatomical characteristics (reduced disk spaces, kyphotic curve), is thought to be a major cause of variability in the results.

https://ift.tt/2S7hKcI

Real-Time Bioimpedance-Based Biopsy Needle Can Identify Tissue Type with High Spatial Accuracy

Abstract

Histological analysis is meaningful in diagnosis only if the targeted tissue is obtained in the biopsy. Often, physicians have to take a tissue sample without accurate information about the location of the instrument tip. A novel biopsy needle with bioimpedance-based tissue identification has been developed to provide data for the automatic classification of the tissue type at the tip of the needle. The aim of this study was to examine the resolution of this identification method and to assess how tissue heterogeneities affect the measurement and tissue classification. Finite element method simulations of bioimpedance measurements were performed using a 3D model. In vivo data of a porcine model were gathered with a moving needle from fat, muscle, blood, liver, and spleen, and a tissue classifier was created and tested based on the gathered data. Simulations showed that very small targets were detectable, and targets of 2 × 2 × 2 mm³ and larger were correctly measurable. Based on the in vivo data, the performance of the tissue classifier was high. The total accuracy of classifying different tissues was approximately 94%. Our results indicate that local bioimpedance-based tissue classification is feasible in vivo, and thus the method provides high potential to improve clinical biopsy procedures.

https://ift.tt/2PQ7Udq

The Foundation of the Future of MCH

Abstract

The accompanying article on the Future of Public Health is a timely call to action. It reminds us of our strong roots and also compels us to consider larger societal issues in pursuing our shared goals.

https://ift.tt/2UQoFsu

Modified Lichtenstein Technique for Transinguinal Preperitoneal Prosthesis (Tipp) Repair of Groin Hernia

Abstract

For the preperitoneal mesh hernioplasty of groin hernias through posterior approaches and other published anterior approaches, the mesh fixation is not done with the inguinal ligament inferiorly, rather, the mesh is overlapped behind the inguinal ligament and on the area which contains the external iliac vessels and important nerves. With the modified Lichtenstein technique, transinguinal preperitoneal placement of the mesh is achieved avoiding dissection or exposure of blood vessels behind the inguinal ligament, the mesh is fixed inferiorly to inguinal ligament as is standard for Lichtenstein technique. Superiorly, medially, and laterally, the mesh is placed preperitoneally behind the buttress of the inguinal muscles.

https://ift.tt/2QCV5bj

Evaluation of Male Breast Glandular Liposculpturing, Response on Commentary

https://ift.tt/2Lqaoye

Integrated Framework for Fast Prototyping and Testing of Autonomous Systems

Abstract

Validating the behavior of a complex system is a fundamental step in the development process to avoid costly damages and dangerous circumstances. Such a phase requires a realistic simulation of the system and the reproduction of the full operative scenario, including the environment with all the possible events and situations in which the system could get into. Although several tools exist to design, simulate and validate specific functions, checking the overall system behavior in an operative scenario usually requires the development of custom simulation frameworks. These are often tailored to the specific system under study, with the consequence that they are either incomplete or not fully reusable for other projects. This paper presents a modular hardware-in-the-loop development simulation framework that allows realistic simulation, supporting multi-vehicle scenario and comprehending tools for reproducing realistic testing environments with advanced sensors. A case of study is presented to show the employment of the proposed framework for testing the behavior of unmanned vehicles, focusing on the timing properties of the system. Category (2).

https://ift.tt/2rIRTML

Meiotic spindle assembly checkpoint and aneuploidy in males versus females

Abstract

The production of gametes (sperm and eggs in mammals) involves two sequential cell divisions, meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate to different daughter cells, and meiosis II resembles mitotic divisions in that sister chromatids separate. While in principle the process is identical in males and females, the time frame and susceptibility to chromosomal defects, including achiasmy and cohesion weakening, and the response to mis-segregating chromosomes are not. In this review, we compare and contrast meiotic spindle assembly checkpoint function and aneuploidy in the two sexes.

https://ift.tt/2S2Wgxw

New host records of three Kudoa spp. ( K. yasunagai , K. thalassomi , and K. igami ) with notable variation in the number of shell valves and polar capsules in spores

Abstract

To date, 26 Kudoa spp. (Myxozoa: Myxosporea: Multivalvulida) have been recorded in edible marine fishes in Japan. In the future, it is likely that even more marine fish multivalvulid myxosporeans will be characterized morphologically and genetically, which will aid the precise understanding of their biodiversity and biology. We examined 60 individuals of six fish species collected from the Philippine Sea off Kochi or from the border between the Philippine Sea and East China Sea around Miyako Island, Okinawa, i.e., the southern part of Japan. Newly collected parasite species included Kudoa yasunagai from the brain of Japanese meagre (Argyrosomus japonicus) and Japanese parrotfish (Calotomus japonicus), Kudoa miyakoensis n. sp. and Kudoa thalassomi from the brain and trunk muscle, respectively, of bluespine unicornfish (Naso unicornis), and Kudoa igami from the trunk muscle of Carolines parrotfish (Calotomus carolinus), African coris (Coris gaimard), and Pastel ringwrasse (Hologymnosus doliatus). With the exception of Japanese parrotfish for K. yasunagai, all these fish are new host records for each kudoid species. Notable variation in the number of shell valves (SV) and polar capsules (PC) was observed for all four kudoid species. In particular, spores with seven or eight SV/PC were prominent in K. igami isolates, despite the original Japanese parrotfish-derived description characterizing it as having spores with six, or less commonly five, SV/PC. However, molecular genetic characterization based on the ribosomal RNA gene (rDNA) and mitochondrial DNA (cytochrome c oxidase subunit 1 and ribosomal RNA small and large subunits) found no significant differences in the nucleotide sequences of isolates with different phenotypical features as far as examined in the present study. A newly erected species, K. miyakoensis n. sp., was determined to be phylogenetically closest to brain-parasitizing species, such as K. chaetodoni, K. lemniscati, and K. yasunagai based on rDNA nucleotide sequences, but differed from them morphologically.

https://ift.tt/2BvUWvV

Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study

Abstract

This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10 at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1–14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β = − 1.1%/year; 95% confidence interval [CI], − 1.8% to − 0.4%; p = 0.005) and no use of ACEI (β = − 3.1%; 95% CI, − 5.4% to − 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9–6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.

https://ift.tt/2QFK49s

Triangular titanium implants for sacroiliac joint fusion

Abstract

Background

Sacroiliac joint (SIJ) dysfunction is an underdiagnosed condition. Several published cohorts have reported favorable midterm outcomes after SIJ fusion using titanium implants placed across the SIJ. Herein, we report 12-month follow-up from SIJ fusion in a standard clinic setting.

Methods

A carefully selected group of 160 consecutive patients with painful SIJ dysfunction were diagnosed at a single center and underwent unilateral or staged bilateral SIJ fusion using triangular titanium implants. Patients were routinely seen in clinic for follow-up every 3 months where they completed visual analog scale (0–10 range) pain ratings and Oswestry Disability Index (ODI). Follow-up CT scan was performed at 1 year.

Results

Mean patient age was 58 years, and 68% were women. 30% underwent staged bilateral SIJ fusion. By month 12, SIJ pain decreased from 8.0 to 2.5 (p < 0.0001) and disability (ODI) decreased from 45.3 to 16.4 (p < 0.0001). The proportion with clinically significant improvements in SIJ pain and ODI was high (> 95%). Perioperative adverse events were mild and decreased with increasing surgical experience with the procedure. Subgroup analysis showed slightly smaller improvements in those undergoing bilateral surgery and those with a spinal cord stimulator in place. CT scan at 1 year showed reabsorption along one or more implants in 16% of cases, but there were no breakages or implant removals.

Conclusions

In standard clinical practice, SIJ fusion with triangular titanium implants produces significant improvement in pain and disability related to SIJ dysfunction.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

https://ift.tt/2SV004o