Tailoring structural properties of spray-dried methotrexate-loaded poly (lactic acid)/poloxamer microparticle blends

Abstract

Drug delivery systems can overcome cancer drug resistance, improving the efficacy of chemotherapy agents. Poly (lactic acid) (PLA) microparticles are an interesting alternative because their hydrophobic surface and small particle size could facilitate interactions with cells. In this study, two poloxamers (PLX 407 and 188) were applied to modulate the structural features, the drug release behavior and the cell viability from spray-dried microparticles. Five formulations with different PLA: PLX blend ratio (100:0, 75:25, 50:50, 25:50, and 0:100) were well-characterized by SEM, particle size analysis, FTIR spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD). The spray-dried microparticles showed higher drug loading, spherical-shape, and smaller particle size. The type of poloxamer and blend ratio affected their structural and functional properties such as morphology, crystallinity, blend miscibility, drug release rate, and cell viability. The methotrexate (MTX), a model drug, was loaded in amorphous spray-dried microparticles. Moreover, the drug release studies demonstrated that PLX induced a leaching-effect of MTX from PLA: PLX blends, suggesting the formation of MTX/PLX micelles in aqueous medium. This finding was better established by cell viability assays. Therefore, biocompatible PLA: PLX blends showed promising in vitro results, and further in vivo studies will be performed to evaluate the performance of this chemotherapeutic agent.

http://bit.ly/2LWDpC9

Transdermal delivery of curcumin-loaded supramolecular hydrogels for dermatitis treatment

Abstract

Curcumin (CUR) is a hydrophobic polyphenol with anti-inflammatory activity. However, its low water-solubility and poor skin permeation limited its application in the treatment of dermititis. CUR-loaded micelles were prepared using thin membrane hydration method with methoxy poly (ethylene glycol)-block-poly (ε-caprolactone) (MPEG-PCL) as carrier material. The drug loading capacity and encapsulation efficiency were 12.14 ± 0.33 and 93.57 ± 1.67%, respectively. CUR-loaded micelles increased CUR's water-solubility to 1.87 mg/mL, being 1.87 × 10⁶-folds higher than native CUR. CUR-loaded supramolecular hydrogels (CUR-H) were prepared through mixing the CUR-loaded micelles solution with α-cyclodextrin (α-CD) solution. The CUR-H presented continuous dissolution behaviour in aqueous medium for 4.5 h. The ex vivo skin permeation test and confocal fluorescence microscopy evaluation confirmed that CUR-H obviously enhanced skin deposition of CUR without drug flux from skin. In vivo experimental results confirmed that the CUR-H was more effective than dexamethasone ointments against croton oil-induced ear edema. The CUR-H composed of MPEG-PCL and α-CD is a promising formulation for skin inflammatory treatment.

http://bit.ly/2shRrVG

Selection of Agricultural Straws as Sustained-Release Carbon Source for Denitrification in a Drawer-Type Biological Filter

Abstract

The aim of this paper is to select feasible agricultural straws as high-quality sustained-release carbon source and examine the effect of determined agricultural organic waste on improving denitrification efficiency. Five kinds of agricultural straws, i.e., the rice straw, the corn straw, the wheat straw, the broomcorn straw, and the reed straw, were evaluated in a self-designed drawer-type biological filter. Results showed that the contents of C, H, and N in the five straws were 34.0~41.0%, 4.9~5.4%, and 1.1~1.5% respectively. The highest TOC release capacity of the rice straw was 12.4 ± 1.3 mg g⁻¹ and the average TOC release of other waste straws ranged from 6.0 to 9.2 mg g⁻¹. The TN release capacities of all the five straws were at a low level, ranging from 0.2 to 1.4 mg g⁻¹. Preliminary denitrification studies showed that the corn and the rice straw could be used as high-quality carbon sources, achieving a COD removal rate of 47.3~50.2% and a TN removal rate of 21.8~24.8% for wastewater with low C/N ratio. The rice straw and the corn straw founctioned both as favorable solid carbon sources and biofilm carriers; the carbon source quality of the corn straw lixivium is more beneficial to microbial utilization. The drawer-type biological filter has showed a good efficiency of denitrification for nitrogen removal when using agricultural straws as biofilm carriers.

http://bit.ly/2QsGIBz

Exploring the Association between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study

Abstract

Introduction

Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior.

Objective

The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action.

Methods

We included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer).

Results

Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0–6.4; and ROR 5.1, 95% CI 4.2–6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9–18.3; and ROR 20.2, 95% CI 12.4–33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8–2.0) for depression and 3.6 (95% CI 3.0–4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases.

Conclusion

Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.

http://bit.ly/2C9ky27

Nuclear Medicine

Distribution of bone tracer uptake in symptomatic knees after ACL reconstruction compared to asymptomatic non-operated knees: a method for better differentiating patient-specific from disease-specific bone tracer uptake in SPECT/CT Abstract Objective To evaluate the differences of bone tracer uptake (BTU) in symptomatic and asymptomatic contralateral knees in patients after reconstruction of the anterior cruciate ligament (ACL-R) and to identify typical BTU patterns and threshold values to differentiate pathological from physiological BTU. Methods 53 patients after unilateral ACL-R were retrospectively included in the study. The population was subdivided into a group of symptomatic operated knees and a group of contralateral asymptomatic non-operated knees. BTU was measured in SPECT/CT using a validated anatomical localization-scheme and normalized mean BTU values were calculated in both knees. Wilcoxon signed rank-test and Pearson's rank-correlation coefficient were used (p < 0.05). Results Symptomatic knees after ACL-R showed significantly more BTU than asymptomatic ones (p < 0.01).Based on the measured BTU activity in SPECT/CT in symptomatic operated and asymptomatic non-operated knees, intensity thresholds of pathological BTU were established. A BTU threshold of greater than the Median + 1 SD of the asymptomatic non-operated knee was defined as pathological. In both groups the highest mean BTU was found on the femoral, tibial and patellar articular surfaces, the lowest BTU in femoral and tibial regions far from the joint. Conclusions The established BTU thresholds for SPECT/CT in knees after ACL-R help to differentiate disease-specific from patient-specific BTU. It could be speculated that BTU in asymptomatic knees equates to the preoperative condition of the knee joint before ACL-R. Therefore, the results of this study help to understand in-vivo loading of the knee and ultimately lead to prediction of development of osteoarthritis in an early stage.

18 F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma Abstract Objective The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4‑dihydroxy‑6‑[18F]‑fluoro-l‑phenylalanine (F-DOPA) uptake parameters with IDHmutation, 1p/19q status, and survival outcomes in patients with glioma. Methods The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13 years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDHmutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan–Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. Results There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5 months (range 3.5–74 months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. Conclusions F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

Fundamental study of radiogallium-labeled aspartic acid peptides introducing octreotate derivatives Abstract Objective Somatostatin receptors are highly expressed in neuroendocrine tumors, and many radiolabeled somatostatin analogs for diagnosis and treatment have been developed. To simultaneously detect not only primary cancer but also bone metastases, this study aimed to develop a positron emission tomography probe using generator-produced nuclide Gallium-68 (T1/2 = 68 min), in which a carrier for primary cancer, a carrier for bone metastases lesions, and a stable gallium complex are introduced into the one molecule. Based on this strategy, the somatostatin receptor-targeted peptide, [Tyr3]-octreotate (TATE), aspartic acid peptide (Dn) with high binding affinity for hydroxyapatite, and Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a stable gallium complex were selected. The novel complexes, Ga-DOTA-Dn-TATE (n = 0, 2, 5, 8, or 11), were designed, synthesized, and evaluated. The radiogallium complexes were prepared using the easy-to-handle radioisotope 67Ga due to relatively long half-life. Methods The radiogallium complex precursor DOTA-Dn-TATE was synthesized by the Fmoc-based solid-phase method and by the air oxidation method to form the disulfide bond. [67Ga]Ga-DOTA-Dn-TATE was synthesized by reacting DOTA-Dn-TATE and 67Ga. Hydroxyapatite binding assays, in vitro cellular uptake experiments in AR42J tumor cells, in biodistribution experiments in AR42J tumor-bearing mice, were performed using [67Ga]Ga-DOTA-Dn-TATE. Results The radiochemical purities of [67Ga]Ga-DOTA-Dn-TATE were > 96.0%. In in vitro and in vivo experiments, [67Ga]Ga-DOTA-D11-TATE had a high affinity for hydroxyapatite and highly accumulated in bone. However, the uptake of [67Ga]Ga-DOTA-D11-TATE into somatostatin receptor-positive AR42J cells was lower than that of [67Ga]Ga-DOTA-TATE, and the accumulation of [67Ga]Ga-DOTA-D11-TATE in tumor was significantly low. Conclusion Ga-DOTA-D11-TATE may not be recognized by somatostatin receptor by the introduction of D11, and the charge adjustment may be important for somatostatin receptor-positive cell uptake.

Brain 18 F-FDG distribution: which region is most affected by increased plasma glucose levels?

Clinical feasibility of early scanning after administration of 68 Ga-DOTATOC Abstract Objective Positron emission tomography (PET)/computed tomography (CT) using 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) is usually performed about 1-h post-injection; however, because of rapid blood clearance, the waiting time for scanning could possibly be shortened without affecting diagnostic performance. The purpose of this study was to investigate the feasibility of early scanning at 30 min post-injection. Methods Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min and 60-min post-injection. The number of known or suspected pathological lesions, and quantitative values of those lesions and physiological uptake were compared. SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were calculated as quantitative values of the pathological lesions. Results A total of 125 known or suspected pathological lesions were found at both timepoints, with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU were highly reproducible, with Spearman's ρ of 0.983, 0.986, 0.918, and 0.981, respectively. The average percent differences (%DIFFave) defined as the differences of the values divided by the value at 1-h post-injection were 11.1% for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological uptake in the two datasets was closely comparable in the pituitary gland (Spearman's ρ = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970, 6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%). Conclusion The diagnostic performance of visual interpretation should be comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post-injection. Some differences between quantitative values may exist; however, they appear to be minimal.

Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review Abstract To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.

The significant value of predicting prognosis in patients with colorectal cancer using 18 F-FDG PET metabolic parameters of primary tumors and hematological parameters Abstract Objects The purpose was to evaluate the correlation of the pre-treatment hematological parameters with metabolic parameters of primary tumor in baseline 18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the prognostic value of both. Methods We retrospectively investigated 231 patients with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested in the same term. PET parameters in term of hematological parameters and pathological characteristics of primary tumor were compared. Kaplan–Meier survival analysis was performed in the patients without distant metastasis. The differences of disease-free survival between groups were compared by log-rank tests. Results Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were significantly correlated with all the metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV (24.82 ± 18.16 vs 19.06 ± 13.30, P = 0.039) and TLG (219.04 ± 186.94 vs 166.45 ± 146.39, P = 0.047) than those whose NLR ≤ 3. NLR in those patients with distant metastasis was significantly higher than those without distant metastasis (P = 0.018) while LMR in those patients with distant metastasis was significantly lower than those without distant metastasis (P = 0.032). Survival analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008) and high LMR (P = 0.027) revealed significant survival benefit. Conclusions There was a significant association between the pre-treatment hematological parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients with CRC. It might be helpful in those patients with high NLR and low LMR to undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.

Comparison of 18 F-Choline PET/CT and MRI functional parameters in prostate cancer Abstract Aim 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. Materials and methods Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. Results The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). Conclusions No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis Abstract Objective To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed. Methods This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT and clinical follow-up. The image data were reconstructed with CT attenuation correction and scatter correction, and with only CT attenuation correction (CTAC). The new method extracted striatal VOI according to the high-level counts and the average striatum volume, and calculated SBR using the reference occipital counts. The SBR values for each patient were obtained using the Tossici-Bolt method (SBRBolt) and our method. Reproducibility of SBR calculation using our method was compared by two operators. Results The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBRBolt (p < 0.001), except for the CTAC images. There were no differences in SBR between the two operators using our method. The diagnostic accuracies with our method for the PS and DLB groups were 98.4 and 96.0%, respectively. Conclusion Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions Abstract Objective To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. Methods 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA. Results 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/Gratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. Conclusions 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.

Dental Research

Load-deflection characteristics of coated and noncoated nickel-titanium wires in self-ligating brackets using a modified bending test: An in vitro study Tripti Tikku, Rohit Khanna, Akhil Agarwal, Kamna Srivastava, Shashank Shekhar, Ivy Shukla Dental Research Journal 2019 16(1):1-6 Background: To determine and compare the force-deflection values of different types of nickel-titanium (NiTi) wires during unloading phase at varying deflections, that is 1 mm, 1.5 mm, 2 mm, and 2.5 mm, with the use of self-ligating ceramic brackets using modified bending test on a typodont under controlled temperature conditions. Materials and Methods: In this in vitro study total of 45 wires of ovoid shape of three different NiTi wires – pseudoelastic NiTi (Group I), heat activated NiTi (Group II), and esthetic coated NiTi (Group III) for maxillary arch were tested after insertion in ceramic self-ligating brackets bonded to plastic teeth of phantom jaw . The maxillary left lateral incisor was removed to simulate a malpositioned tooth which acted as the load site, and load-deflection characteristics were measured during unloading using Instron, and data analyzed statically by two-way analysis of variance ,Tukey's post hoc test, intraclass correlation coefficient and Pearson correlation coefficient. A two-sided (α = 2) P < 0.05 was considered statistically significant. Results: When wires were compared at each deflection statistically significant difference was observed between the three groups of wires (Group I > Group II > Group III) at all the four levels of deflection except for Group II versus Group III at 1 mm, 1.5 mm, and 2 mm of deflection. Statistically significant difference was noted in mean load values for comparisons made at different deflections for each wire except for the comparison made at 1.5 versus 2 mm for Group II and Group III. Conclusion: Overall comparison showed esthetic coated Ni-Ti wires gave significantly lower mean load values, followed by heat activated and pseudoelastic NiTi wires. Thus, heat activated NiTi wires are best suited in patients with severe malpositions/periodontitis, while for esthetically conscious patients esthetic coated NiTi can be used.

Effects of menthol-flavored substances at the cellular level on oral mucosal sites Nanda Prasad, Sarvesh Vijay, A Yashwanth Reddy, S Nonitha Dental Research Journal 2019 16(1):7-11 Background: The purpose of this study was to determine the effects of menthol-flavored substances at the cellular level in different mucosal sites of the oral cavity and to compare the cellular changes between individuals without the habit of chewing menthol-flavored substances and individuals with the habit. Materials and Methods: This was an experimental cytology study including a total of 500 individuals belonging to the age group of 18–45 years based on the inclusion or exclusion criteria. The selected participants were divided into two groups of 250 participants each, based on participants not having the habit of chewing menthol-flavored substances (Group I) and participants having the habit of chewing menthol-flavored substances (Group II). Cytological smears were taken by gently scraping the mucosal surfaces in different sites of the oral mucosa using a wooden spatula and stained with Papanicolaou, analyzed under microscope for any cellular changes. The results were tabulated and statistically analyzed using Chi-square test and Fisher's exact test. P < 0.05 was considered statistically significant. Results: Micronuclei seen in all the participants belonging to group with the habit of chewing menthol-flavored substances with a P < 0.001 which was considered highly significant. Alteration in the nuclear-cytoplasmic ratio was also seen P = 0.001, which showed significant at 1% significance level. Conclusion: Participants with habit of chewing menthol-flavored substances showed the presence of micronuclei and slight alteration in the nuclear-cytoplasmic ratio, which could be directly related to genotoxicity and cell damage.

Impact of occupational dental erosion on oral health-related quality of life among battery factory workers in Bengaluru, India Amit Kumar, Manjunath P Puranik, KR Sowmya, Soni Rajput Dental Research Journal 2019 16(1):12-17 Background: A greater understanding of impact of occupational dental erosion on oral health-related quality of life (OHRQoL) will sensitize both employee and employers to adopt strict protective measures for oral health. The research aimed to determine the relationship between occupational dental erosion and OHRQoL among battery and other factory workers in Bengaluru, India. Materials and Methods: This cross-sectional comparative study enrolled a total of 400 workers. Structured proforma assessed information on sociodemographic details, oral hygiene practices, adverse oral habits, and work-related practices. OHRQoL was determined using oral health impact profile-14 (OHIP-14). Dental erosion was measured using Smith and Knight's tooth wear index modified by Millward et al. 1994 scoring system independent t-test, Mann–Whitney U-test and Spearman's correlation was performed. P < 0.05 was considered statistically significant. Results: The mean age of the participants in the study and control groups was 43.11 ± 8.02 and 45.93 ± 6.16 years, respectively. Less than half of the participants in the study group had positive behavioral work practice. The prevalence and severity of dental erosion was significantly higher in study group (39.5%) than control group (11.5%). Mean OHIP-14 score was significantly lower in study group (23.88 ± 0.88) than control group (26.06 ± 9.67). Dental erosion significantly correlated with work experience and OHIP-14. Conclusion: The findings highlight the impact of occupational dental erosion on OHRQoL. Measures to enhance occupational safety thereby reducing exposure to occupational hazards are needed.

Comparative investigation of primary stability of four different dental implants in low-density bone model Saied Nokar, Amirali Reza Rasouli-Ghahroudi, Elham Shidvash, Faezeh Atri Dental Research Journal 2019 16(1):18-23 Background: Primary stability is one of the prerequisites of immediate loading. The aim of this study was to compare the primary stability of four different implant systems in low-density bone models. Materials and Methods: In this in vitro experimental study, 20 fixtures from four implant body designs were selected: Zimmer Tapered Screw-Vent (ZTSV), NobleReplace Tapered (NRT), Replace Select Tapered (RST), and Dentium SuperLine (DSL). Fixtures were inserted in low-density bone models according to manufacturer drilling protocol by one surgeon. Measurement of insertion torque value (ITV), resonance frequency analysis (implant stability quotient [ISQ]), and reverse torque value (RTV) was recorded for each fixture. The data were analyzed with one-way ANOVA and post hoc tests (Tukey honestly significant difference) (P < 0.05). Results: ZTSV had significantly lower amount of insertion torque in comparison to other systems (P = 0.045). RTV was significantly lower in ZTSV in comparison to DSL and NRT (P = 0.004). ISQ value in NRT (ISQ = 67) was significantly higher than other systems (P = 0.000). The lowest amount of ISQ was in RST system (ISQ = 53) with significant difference (P = 0.000). Conclusion: This study demonstrated that primary stability of different implant systems was not comparable and implant design was effective on ITV, RTV, and ISQ.

Assessment of antimicrobial activity of different concentrations of Tinospora cordifolia against Streptococcus mutans: An in vitro study Sankalp Agarwal, Priyadarshini H Ramamurthy, Bennete Fernandes, Avita Rath, Preena Sidhu Dental Research Journal 2019 16(1):24-28 Background: The antimicrobial property of Tinospora cordifolia has been tested against a variety of microorganisms in the literature. The present study aimed to assess the antimicrobial activity of different concentrations of commercially available T. cordifolia powder against Streptococcus mutans. Materials and Methods: An in vitro study was undertaken in which extract of T. cordifolia was obtained using 100% ethanol by maceration. Seven different concentrations were prepared and tested against S. mutans in brain–heart infusion agar medium. Plates were incubated aerobically at 37°C for 48 h, and zone of inhibition was measured using Vernier caliper. 0.2% chlorhexidine and dimethylformamide were used as positive and negative controls respectively. The data were analysed by descriptive analytic tests. Results: The maximum antibacterial activity of T. cordifolia was observed with a volume of 40 μl at 2% concentration with a zone of inhibition of 19 mm. A 30 μl volume of 0.2% chlorhexidine showed a zone of inhibition of 28 mm, and no zone of inhibition was observed with dimethylformamide. Conclusion: Tinospora exhibited antimicrobial activity against S. mutans. However, it needs to be confirmed further with in vivo studies.

Association between quality of sleep and chronic periodontitis: A case–control study in Malaysian population Vijendra Pal Singh, Joe Yin Gan, Wei Ling Liew, Htoo Htoo Kyaw Soe, Sowmya Nettem, Sunil Kumar Nettemu Dental Research Journal 2019 16(1):29-35 Background: Periodontitis is a public health concern since it is a major factor in tooth loss worldwide and has association with many systemic diseases. Sleep is a complex and essentially biological process and a critical factor for maintaining mental and physical health. Since inflammation is characteristic of both chronic periodontitis and sleep deprivation, few studies in recent years present the contradictory results regarding this potential association. The objective of the present study was to investigate the association between quality of sleep and chronic periodontitis. Materials and Methods: A total of 200 individuals participated in this study. All participants underwent a comprehensive clinical periodontal examination. Case–control were identified using the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions for periodontal disease. The quality of sleep was assessed by Pittsburgh Sleep Quality Index. The univariate and multivariate logistic regression analysis was used to test the influence of variables (quality of sleep, age, sex, ethnicity, education, and socioeconomic status), in the occurrence of periodontitis. Odds ratio (OR) and respective confidence intervals (CIs) were calculated and reported. P ≤0.05 was considered statistically significant. Results: The prevalence of poor quality of sleep was 56.75% in cases (periodontitis group) and 43.24% in control group. There was positive association between quality of sleep and chronic periodontitis (OR = 3.04; 95% CI = 1.42–6.5; P = 0.004). In multivariate logistic regression analysis, only the age was significantly related to the periodontitis (OR = 1.11; 95% CI = 1.07–1.41; P < 0.001), other variables failed to reach the significant level. Conclusion: Poor quality of sleep was significantly associated with chronic periodontitis. Only the age was significantly related to periodontitis among the other covariable measured.

Sealants revisited: An efficacy battle between the two major types of sealants – A randomized controlled clinical trial B Prathibha, P Parthasarthi Reddy, Md Shakeel Anjum, M Monica, BH Praveen Dental Research Journal 2019 16(1):36-41 Background: The aim of this study is comparing the retention and caries preventive effect of the glass-ionomer fissure sealant and resin-based fissure sealant. Materials and Methods: A randomized-controlled split-mouth study was conducted to compare the retention and the caries preventive effect of light-cured resin-based sealant (3M ESPE) and glass ionomer sealant (Fuji VII). The sealants were applied to either the right or the left lower mandibular molars (7-9 yrs of age) in 120 school children, based on the randomization process. They were recalled for assessment of clinical retention at intervals of 3, 6, and 12 months. The caries-preventive effect between the two materials was tested statistically by the McNemar's test for matched pairs, and the differences observed with regard to the retention of the materials was tested by Chi-square tests. The level of significance was set to be at P < 0.05. Results: At the end of 12th month, sealant retention is found to be higher in the resin-based sealant group compared to the glass ionomer group. In the glass ionomer sealants placed, 101 (91%) were caries-free and 10 (9%) had caries. In the resin-based sealant, 105 (94.60%) had sound teeth and 6 (5.4%) had dental caries (P = 0.34). Conclusion: The glass ionomer sealant was less retentive when compared to resin sealants. The caries incidence between the glass ionomer and resin-based sealants was not statistically significant.

A comparative study of the clinical efficiency of chemomechanical caries removal using Carie-Care gel for permanent teeth of children of age group of 12–15 years with that of conventional drilling method: A randomized controlled trial Priyanka Sontakke, Prateek Jain, Aniket Dhote Patil, Gautam Biswas, Pramod Yadav, Diljot Kaur Makkar, Vikas Jeph, Banu Pyari Sakina Dental Research Journal 2019 16(1):42-46 Background: Dental caries is considered as one of the most serious dental diseases that results in localized dissolution and destruction of the calcified tooth tissues. As possible alternatives to conventional techniques of caries removal, chemomechanical caries removal systems have emerged. This study aims to clinically observe the advantages of chemomechanical method of caries removal over conventional technique. Materials and Methods: Inthis randomized controlled trial a total of 60 children with Class 1 open carious lesions were selected for the study. They were divided into two equal groups according to a method of caries removal (30 chemomechanical and 30 conventional on permanent molars). In Group A, caries was removed using the Carie-Care system and in Group B with the conventional drill and were restored equally with glass ionomer cement. The visual analogy face scale was used to determine the level of anxiety in children at baseline, during treatment and after treatment. Results: The results were subjected to statistical analysis using Student's unpaired t-test. It showed that though chemomechanical technique took a marginal increase in time compared to the conventional technique, it was found to be more comfortable for all the children. Conclusion: Chemomechanical technique though time-consuming is definitely superior compared to the conventional technique provided we use a less technique sensitive restorative material which retains in the oral cavity for longer period. It is definitely a better treatment protocol in school-based dental treatment and atraumatic restorative dentistry compared to the conventional technique.

The effect of office bleaching on the color and bond strength of resin restorations Homayoon Alaghehmand, Marzieh Rohaninasab, Ali Bijani Dental Research Journal 2019 16(1):47-52 Background: Bleaching may affect the bond strength of existing composite fillings and may weaken it. Hence, the aim of this study was to find the best method of in-office bleaching with the least effect on microshear bond strength (MSBS) of existing composite resin fillings to tooth structure. Materials and Methods: In this in vitro study, Class V cavities were prepared on buccal surface of 50 extracted third human sound molars. The cavities in 25 teeth had enamel axial walls, Group E, which were divided into five subgroups of E1 through E5 and in 25 teeth had dentin axial walls, Group D, which were divided into five subgroups of D1 through D5. Cavities were treated with Single Bond 2 adhesive system and restored with composite resin (Z250). The corresponding subgroups received similar bleaching methods and materials; 1 – not bleached, 2 – hydrogen peroxide (HP) 25%, 3 – HP + ultraviolet light, 4 – HP + light-emitting diode-curing device, and 5 – HP + diode laser. Teeth colors were monitored before and after bleaching, and MSBS test and failure modes were examined. Results were analyzed with one-way ANOVA and Kruskal–Wallis tests. P < 0.05 was considered significant. Results: One-way ANOVA did not show differences in MSBS of enamel subgroups but showed significant differences in dentin subgroups (P < 0.00). Adhesive fracture in all of the subgroups was the most frequent mode of failure. Kruskal–Wallis test showed that laser was the most effective instrument to change ΔE. Conclusion: Diode laser was the best method for tooth bleaching because lowering the shear bond strength between composite resin and enamel was minimum and also had the most ΔE in tooth bleaching.

In vitro evaluation of coronal discoloration following the application of calcium-enriched mixture cement, Biodentine, and mineral trioxide aggregate in endodontically treated teeth Solmaz Araghi, Atefeh Khavid, Mostafa Godiny, Mahshid Saeidipour Dental Research Journal 2019 16(1):53-59 Background: This study sought to assess and compare coronal discoloration following the application of white mineral trioxide aggregate, Biodentine, and calcium-enriched mixture cement in endodontically treated teeth. Materials and Methods: In this in vitro experimental study, 64 freshly extracted sound human premolars were selected, cleaned, and stored in saline. After cleaning, shaping, and obturation the root canal of the teeth, the teeth were randomly assigned to one control (n = 4) and three experimental (n = 20) groups. In the experimental groups, the cement were applied over the canal orifices in 3-mm thickness. All teeth were then restored with composite resin. Color parameters, according to the CIE L*a*b* system, were measured using Vita Easyshade spectrophotometer before application of cement and at 1 week, 1 month, 2 months, and 3 months after the application of cement. The recorded values were statistically analyzed using descriptive and analytical statistics. For analytical statistics, Kolmogorov–Smirnov test was applied to assess normal distribution of data. ANOVA was used to compare the results at baseline and repeated measures. P < 0.05 was considered statistically significant Results: Significant differences were noted in color change (ΔE) between all time points except between ΔE4 (2 months) and ΔE5 (3 months) (P < 0.01). However, tooth discoloration caused by the three cement was not significantly different (P = 0.343). Conclusion: The three tested cement were not significantly different in terms of causing coronal discoloration in endodontically treated teeth.

The Parkinson fatigue scale: an evaluation of its validity and reliability in Greek Parkinson’s disease patients

Abstract

Objective

Fatigue is one of the most frequent and important nonmotor symptoms of patients with Parkinson disease (PD), affecting quality of life. Although, in some cases, it may be a severe and debilitating complaint, it remains relatively unexplored. The PFS-16 is a fatigue measure, specifically designed for PD patients. The aim of this study was to investigate the psychometric properties of Parkinson fatigue scale (PFS-16) in Greek PD patients.

Methods

In total, 99 patients with PD were assessed. The following psychometric properties were tested: data quality, floor/ceiling effects, reliability (internal consistency, test–retest reliability), and construct validity. Construct validity was evaluated by examining correlations with other variables including other fatigue measures such as Fatigue Severity Scale (FSS) and the vitality scale (SF-VT) of SF-36. Moreover, assumptions were explored about "known" groups concerning fatigue.

Results

The mean score for the PFS-16 was 2.95 (± 0.91); acceptability was good with negligible floor and ceiling effects. Results showed high internal consistency (Cronbach's alpha, 0.96) and test–retest reliability (ICC, 0.93). Strong correlations were observed between the PFS-16 and other fatigue (FFS and SF-VT) measures (rs = 0.77 and − 0.70, p < 0.001), revealing appropriate validity. Furthermore, predictions for "known" groups validity were verified.

Conclusion

The Greek version of the PFS-16 showed satisfactory reliability and validity and thus can be regarded as a useful tool in assessing fatigue in PD.

http://bit.ly/2FdVYkz

IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study

Summary

Purpose The current standard treatment for locally advanced nasopharyngeal carcinoma (LANPC) is intensity-modulated radiation therapy (IMRT) plus cisplatin concurrent chemoradiotherapy (CCRT). However, this regimen has well-known hematological and gastrointestinal toxicities. Many studies have reported that S-1 was effective in the treatment of multiple solid cancers with mild toxicities. However, knowledge regarding IMRT plus S-1 CCRT in LANPC is lacking. Therefore, we conducted this prospective phase II trial to evaluate the efficacy and safety of this regimen in LANPC. Patients and Methods Eligible patients with histologically confirmed LANPC were enrolled in this study. IMRT was given in 30–32 fractions five times per week. Concurrently, S-1 was administrated twice per day orally based on the body surface area (BSA < 1.25 m², 30 mg; BSA: 1.25–1.5 m², 40 mg; BSA > 1.5 m², 50 mg). The primary endpoints were progression-free survival (PFS) and adverse events. Results From August 1, 2013, to December 15, 2017, 131 patients were enrolled in this study. The distribution of disease stages among the patients was as follows: 21 patients were in stage II (16.0%), 42 patients were in stage III (32.0%), and 68 patients were in stage IV (52.0%). After CCRT, the 3-year PFS, overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates were 87.4%, 95.7%, 94.7%, and 91.5%, respectively. The severity of most toxicities was mild. Approximately two-thirds of patients had no hematological toxicity. Grade 2 hematological toxicities included leukopenia (11.5%), anemia (1.5%), and thrombocytopenia (0.8%). Grade 3 hematological toxicities were rarely observed. Conclusion The results demonstrated that IMRT plus S-1 CCRT was effective with mild toxicity for patients with LANPC.

http://bit.ly/2Fen0IQ

Medulloepithelioma with heterologous osteoid component: a case report and review of literature

Abstract

Purpose

Medulloepithelioma is a rare brain tumor that has been classified as embryonal tumor with multilayered rosettes (ETMR) if it harbors C19MC amplification. In rare instances, it shows evidence of heterologous differentiation.

Methods

We report a case of a 10-year-old female who presented with headache, squint, and minimal left sided weakness of 1 week duration.

Results

Microscopy revealed a small round blue cell tumor with focal glandular and tubular differentiation. In one focus, well-developed osteoid was identified. The tumor labeled with LIN28A immunostain.

Conclusions

Unusual features can be encountered in medulloepithelioma which should be in the differential diagnosis of CNS embryonal tumors. Full description of the case with review of the literature and comparison between cases with and without heterologous elements is presented.

http://bit.ly/2H3pUBJ

Preparation of diamine-based polybenzoxazine coating for corrosion protection on mild steel

Abstract

The diamine-based polybenzoxazine (PpC-mda) coating was prepared on mild steel (MS) by spray coating and thermal curing method. The thermal curing process and thermal stability of PpC-mda were studied by differential scanning calorimeter (DSC) and thermogravimetric analysis (TGA), respectively. The corrosion resistance properties of PpC-mda coating were investigated by electrochemical measurements. The results revealed that the hydrophobic PpC-mda coating exhibited high corrosion resistance on mild steel with the protection efficiency of 99.93%.

http://bit.ly/2RFzFdm

Effects of modified nano-silica on the microstructure of PVDF and its microporous membranes

Abstract

In this study, effects of modified silica on the microstructure of polyvinylidene fluoride and its microporous membranes were investigated. The silica was modified by 3-Methacryloxypropyltrimethoxysilane to improve its compatibility with the polyvinylidene fluoride matrix. The relaxation time of polyvinylidene fluoride was markedly improved by modified nano-silica, especially at the loading of 0.1 wt‰. Effects of the modified silica on the nanocomposite microstructure, such as crystallization and orientation behavior, were studied in the manuscript. Furthermore, adding 3-Methacryloxypropyltrimethoxysilane modified silica could effectively handicap the relaxation of orientation structure in polyvinylidene fluoride and facilitate the formation of uniform lamellar structures which could be described by two-dimensional small-angle X-ray scattering testing. Finally, casting films with more uniform lamellar structure was also in favor of fabricating polyvinylidene fluoride microporous membranes by melt-stretching method.

http://bit.ly/2H2d5aR

IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study

Summary

Purpose The current standard treatment for locally advanced nasopharyngeal carcinoma (LANPC) is intensity-modulated radiation therapy (IMRT) plus cisplatin concurrent chemoradiotherapy (CCRT). However, this regimen has well-known hematological and gastrointestinal toxicities. Many studies have reported that S-1 was effective in the treatment of multiple solid cancers with mild toxicities. However, knowledge regarding IMRT plus S-1 CCRT in LANPC is lacking. Therefore, we conducted this prospective phase II trial to evaluate the efficacy and safety of this regimen in LANPC. Patients and Methods Eligible patients with histologically confirmed LANPC were enrolled in this study. IMRT was given in 30–32 fractions five times per week. Concurrently, S-1 was administrated twice per day orally based on the body surface area (BSA < 1.25 m², 30 mg; BSA: 1.25–1.5 m², 40 mg; BSA > 1.5 m², 50 mg). The primary endpoints were progression-free survival (PFS) and adverse events. Results From August 1, 2013, to December 15, 2017, 131 patients were enrolled in this study. The distribution of disease stages among the patients was as follows: 21 patients were in stage II (16.0%), 42 patients were in stage III (32.0%), and 68 patients were in stage IV (52.0%). After CCRT, the 3-year PFS, overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates were 87.4%, 95.7%, 94.7%, and 91.5%, respectively. The severity of most toxicities was mild. Approximately two-thirds of patients had no hematological toxicity. Grade 2 hematological toxicities included leukopenia (11.5%), anemia (1.5%), and thrombocytopenia (0.8%). Grade 3 hematological toxicities were rarely observed. Conclusion The results demonstrated that IMRT plus S-1 CCRT was effective with mild toxicity for patients with LANPC.

http://bit.ly/2Fen0IQ

Current Controversies in Metabolic Surgery for Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents the most common liver disease, and it is expected to become the leading cause of end-stage liver disease in the near future. Bariatric operations have beneficial effects on NAFLD, inducing histological resolution of liver damage through weight loss-dependent and weight loss-independent mechanisms. Due to lack of randomized controlled trials, no specific guidelines have been established so far. Yet there is growing evidence that NAFLD will eventually become a formal indication for metabolic surgery. Data regarding the choice of procedure are conflicting, although gastric bypass seems to be slightly superior to sleeve gastrectomy. The purpose of this review is to provide an update on the ongoing research regarding the role of metabolic surgery in NAFLD management.

http://bit.ly/2ACoo3V

Short- and Long-Term Effects of Bariatric Surgery on Vascular Phenotype

Abstract

Background

Retinal microvascular diameters and large artery stiffness are valid biomarkers of cardiovascular risk. This study assessed short- and long-term micro- and macrovascular improvements after bariatric surgery (BS).

Methods

Sixteen patients (44 ± 12 years) underwent BS in this observational study. Two weeks before as well as 6 weeks and 4 years after surgery, retinal vessel analysis and assessment of brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI), and anthropometry were performed. Three patients were lost to follow-up.

Results

Six weeks after BS, retinal arteriolar diameters (CRAE) were wider (180.1 μm vs. 188.1 μm; p = 0.001), and the arteriolar-to-venular diameter ratio (AVR) was higher (0.82 vs. 0.86; p < 0.001) compared to baseline levels. During the 4 years of follow-up, the retinal changes sustained but further improvements did not occur. Both indices of large artery stiffness, baPWV and CAVI, remained unchanged 6 weeks and 4 years after surgery.

Conclusions

Retinal microvascular phenotype improved 6 weeks after BS. The improvements in microvascular health were maintained during 4 years of follow-up but, despite significant further reductions in body mass index, did not improve further long-term. baPWV and CAVI were unaffected after surgery indicating that BS primarily affects microvascular phenotype rather than large artery stiffness. Retinal vessel imaging seems to be a feasible diagnostic tool to monitor microvascular health after BS. Normalization of BMI and blood pressure may be necessary to achieve long-term improvement of large artery phenotype after BS.

http://bit.ly/2SIpP7Y

Cardiogastric Fistula as a Rare Complication After Gastric Banding and Hiatal Hernia Surgery

http://bit.ly/2ACCulI

Dosage adjustments in pivotal clinical trials with oral targeted therapies in solid tumors conducted in Europe

Abstract

Purpose

The aim of this study was to evaluate in what measure is dosage adjustment particularly prevalent in pivotal clinical trials of oral targeted therapy drugs approved by the European Medicine Agency as of July 31, 2018, for the treatment of solid tumors.

Methods

We performed a search on the official EMA site on human medicines, using as Keyword Search the ATC Code L01X (other antineoplastic agents); from the list of drugs results, we subsequently excluded antineoplastic drugs for hematological diseases, as well as refused and withdrawn drugs. For all analyzed drugs, we recorded full dosages, dose adjustments with relative reduction percentage, reason for the adjustments, number of patients included in the trial, percentage of patients who reduced their dosage or temporarily discontinued therapy, cause of dose reduction, and presence or absence of reference to a clinical outcome in patients who reduced their dose or discontinued therapy.

Results

We considered 74 pivotal trials on 29 target therapies, of which 56 (76%) provide information on dosage reduction, 41 (55%) on therapy suspension, and 29 (39%) on the dose taken by the sample. Trials that provide information on dosage adjustment include reduction and suspension data widely used to manage side effects; they concern, respectively, 32 and 44% of the samples considered. No trial results take account of the possible role of adjustment in clinical outcomes.

Conclusion

It would be advisable for pivotal clinical trials to give more relevance to dose management, which is a widely used tool for the management of adverse events in clinical practice. To date, such information is lacking.

http://bit.ly/2SJKtVe

Self-perceived burden mediates the relationship between self-stigma and quality of life among Chinese American breast cancer survivors

Abstract

Purpose

Cancer-related self-stigma (the internalized sense of shame about having cancer) has been found to associate with poorer quality of life (QoL) among cancer survivors. However, culturally salient illness beliefs (e.g., cancer is contagious; cancer is a result of karma; and cancer brings shame to the family) may make Chinese cancer survivors vulnerable to self-stigmatization. This study examined the association between self-stigma and QoL among Chinese American breast cancer survivors (BCS). To understand the potential mechanism, the mediating role of self-perceived burden to caregivers between self-stigma and QoL was also examined.

Methods

Chinese American BCS (n = 136) were recruited through community-based cancer associations. Participants' self-stigma, self-perceived burden, and QoL were measured in a questionnaire package.

Results

Structural equation modeling results supported the proposed mediation model in predicting physical QoL (χ²(100) = 123.041, CFI = 0.982, TLI = 0.975, RMSEA = 0.041) and emotional QoL (χ²(84) = 137.277, CFI = 0.958, TLI = 0.940, RMSEA = 0.069), with satisfactory model fit indices. Both the indirect effects from self-stigma to QoL via self-perceived burden (physical: β = − 0.13; 95% CI = − 0.22, − 0.07 and emotional: β = − 0.11; 95% CI = − 0.22, − 0.04) and the direct effects from self-stigma to poorer QoL were significant (physical: β = − 0.22; 95% CI = −0.34, −0.10 and emotional: β = − 0.39; 95% CI = − 0.54, − 0.23), suggesting a partial mediation effect of self-perceived burden between self-stigma and QoL.

Conclusions

Self-stigma could reduce physical and emotional QoL through increasing self-perceived burden. Interventions aiming to reduce Chinese American BCS' self-stigma and perceptions of burdensomeness may facilitate improvement in QoL, which in turn promotes better cancer survivorship.

http://bit.ly/2H0nq7l

Intracranial volume (ICV) in isolated sagittal craniosynostosis: a retrospective case-matched-control study

Abstract

Purpose

Children with sagittal craniosynostosis (SC) are at risk of developing raised intracranial pressure (ICP). This is thought to result from cephalocranial disproportion—the restriction of normal cerebral development by a small cranial vault. It remains unclear whether intracranial volume (ICV) is altered in SC. This study offers a novel volumetric analysis of the scaphocephalic skull, comparing supratentorial (ST) volume, infratentorial (IT) volume, and total ICV of patients with sagittal synostosis to normal controls.

Methods

ICVs of 32 consecutive patients undergoing total calvarial vault remodelling (TCVR) for isolated SC were compared to 32 age- and sex-matched normal controls. ICV was measured with manual techniques on head computerised tomographic (CT) scans using OsiriX software. A paired t test was used to compare data between cases and controls.

Results

Mean total ICV, ST volume and IT volume were larger in SC than in controls, except in females > 6 months of age. There was no statistical significance. Regression analysis demonstrated larger ICVs in diseased children than in controls younger than 10 months, at which age trend lines intersected and the reverse became true for older children. This likely represents an evolving risk of cephalocranial disproportion beyond 10 months of age. The IT/ST volume ratio was conserved in scaphocephaly, and very closely approximated that of controls.

Conclusions

Sagittal craniosynostosis appears to be associated with a larger cranial vault at less than 10 months and a smaller vault at greater than 10 months, although statistical significance was not achieved.

http://bit.ly/2FcWq2z

Expression of cry genes in Bacillus thuringiensis biotechnology

Abstract

Bacillus thuringiensis is a gram-positive, spore-forming bacterium that produces insecticidal crystal proteins during sporulation. The production of these crystals results primarily from the expression of cry genes. In this review, we focus on the expression and application of cry genes directed by both cry gene promoters and non-cry gene promoters in different hosts. However, not all cry genes and niches are compatible with B. thuringiensis. New delivery systems offsetting the current limitations in B. thuringiensis application are needed to improve Cry production, niche fitness, and persistence. This review examines currently available research and highlights areas in need of further research and development for more effective production and utilization of Cry insecticidal proteins.

http://bit.ly/2CW1C8I

Bone resorption in autologous cryopreserved cranioplasty: quantitative evaluation, semiquantitative score and clinical significance

Abstract

Background

Changes after reimplantation of the autologous bone have been largely described. However, the rate and the extent of resorption in cranial grafts have not been clearly defined. Aim of our study is to evaluate the bone flap resorption (BFR) after cryopreservation.

Methods

We retrospectively reviewed 27 patients, aged 18 years or older, subjected to cranioplasty (CP) adopting autologous cryopreserved flap. The BFR was derived from the percentage of decrease in flap volume (BFR%), comparing the first post-operative computed tomography (CT) and the last one available (performed at least 1 year after surgery). We also proposed a semiquantitative scoring system, based on CT, to define a clinically workable BFR classification.

Results

After a mean ± SE follow-up of 32.5 ± 2.4 months, the bone flap volume decreased significantly (p < 0.0001). The mean BFR% was 31.7 ± 3.8% and correlated with CT-score (p < 0.001). Three BFR classes were described: mild (14.8% of cases) consisting in minimal bone remodelling, CT-score ≤ 6, mean BFR% = 3.5 ± 0.7%; moderate (51.9% of cases) corresponding to satisfactory cerebral protection, CT-score < 13, mean BFR% = 25.6 ± 2.2%; severe (33.3% of cases) consisting in loss of cerebral protection, CT-score ≥ 13, mean BFR% = 54.2 ± 3.9%. Females had higher BFR% than males (p = 0.022). BFR classes and new reconstructive surgery were not related (p = 0.58).

Conclusions

BFR was moderate or severe in 85.2% of re-implanted cryopreserved flaps. The proposed CT-score is an easy and reproducible tool to define resorption extent.

http://bit.ly/2Qxg4Ym

Analysis of the Algae Growth Dynamics in the Hydroponic System with LEDs Nighttime Lighting Using the Laser Granulometry Method

Abstract

The latest research focused on the analysis of algal growth and the dynamics of their growth use the laser diffraction technique, enabling determination of the volume fraction of suspended particles with specific diameters in aqueous solution as well as their fractal dimensions. This study focuses on the possibility of using a laser granulometer to assess the growth dynamics of algae growing in treated wastewater in a hydroponic system, supported by artificial lighting with the use of light-emitting diodes (LEDs). On the basis of the measurements, the fractal dimension (Df) of algae was determined. An attempt was made to apply the modified Avrami equation describing the crystallization process for the analysis of algae growth dynamics in wastewater. Presented results show that the fractal dimension of suspended matter, largely created by algae, in the case of additional lighting of the hydroponic system at night, takes lower values (Df ~ 1.0) than in sewage without additional light source (Df ~ 2.0). In each measurement series, the fractal dimension of particles in the tank with lighting in the end of the experiment was about 33–43% lower than in the tank without LEDs. The analysis of changes in particle diameters calculated on the basis of Avrami equation largely corresponds with the stages of algae growth. During the measurement series with lower air temperatures, the growth of algae in the tank with additional light was faster than in the tank without LEDs. The obtained information can be the basis for determining the effective method of removing algae from wastewater treated in the hydroponic system, before they are discharged to the receiver in order to prevent the outflow of increased concentrations of total suspended solids.

http://bit.ly/2Fjh00G

Coordinated downregulation of the photosynthetic apparatus as a protective mechanism against UV exposure in the diatom Corethron hystrix

Abstract

The effect of ultraviolet radiation (UVR) on photosynthetic efficiency and the resulting mechanisms against UV exposure employed by phytoplankton are not completely understood. To address this knowledge gap, we developed a novel close-coupled, wavelength-configurable platform designed to produce precise and repeatable in vitro irradiation of Corethron hystrix, a member of a genera found abundantly in the Southern Ocean where UV exposure is high. We aimed to determine its metabolic, protective, and repair mechanisms as a function of varying levels of specific electromagnetic energy. Our results show that the physiological responses to each energy level of UV have a negative linear decrease in the photosynthetic efficiency of photosystem II proportional to UV intensity, corresponding to a large increase in the turnover time of quinone reoxidation. Gene expression changes of photosystem II-related reaction center proteins D1, CP43, and CP47 showed coordinated downregulation whereas the central metabolic pathway demonstrated mixed expression of up and downregulated transcripts after UVR exposure. These results suggest that while UVR may damage photosynthetic machinery, oxidative damage may limit production of new photosynthetic and electron transport complexes as a result of UVR exposure.

http://bit.ly/2C4rvBz

Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up

Abstract

Background

Guillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered.

Objectives

We aimed at updating the epidemiology of GBS in the years 2003–2017 and carrying on the work started in the 1980s.

Methods

We conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from administrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertainment and definition are analogous to those adopted in previous surveys.

Results

In the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08–1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70–79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms.

Conclusion

In line with many epidemiological data, in the whole period 2003–2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found.

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The relationship between injury mechanism and sexual dysfunction in surgically treated pelvic fractures

Abstract

Purpose

The aim of the study was to identify the incidence of new sexual dysfunction reported by the patient in surgical treatment of pelvic ring injuries, and to describe the relationship between new sexual dysfunction and type of fracture.

Methods

Ninety-five patients who were operated for pelvic fracture were included in the study. Patients were evaluated according to age, gender, marital status, body mass index, trauma mechanism, fracture classification, genitourinary injury, accompanying injury, injury severity score, surgical technique, fixation material, duration of operation, functional outcomes, blood loss, complications, and sexual dysfunction. Functional outcomes were assessed with Female Sexual Functioning Index (FSFI), International Index of Erectile Function-5 (IIEF5), Arizona Sexual Experience Scale (ASEX), and Modified Majeed's pelvic outcomes grading scale (MPS).

Results

Genitourinary symptoms were erectile dysfunction (ED) in 13 men, ejaculatory dysfunction in 9 men, and dyspareunia in 23 women. Urethral stricture developed in 4 males and 1 female with the urethral injury. FSFI score, ASEX score, and MPS score showed the statistically significant difference between the fracture types (p = 0.021, p = 0.032 and p = 0.020, respectively). There were no significant difference between fracture types in terms of the IIEF5 score, and no significant relationship between fracture type and ED development (p = 0.141).

Conclusion

Anteroposterior compression (APC) is the most common cause of sexual dysfunction in both sexes, independent of surgery. In addition, the most common cause of ED in men is vertical shear (VS). Especially patients with APC and VS injuries should be multidisciplinary evaluated with gynecology, urology, and psychiatry departments.

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Epidemiologic trends for isolated tibia shaft fracture admissions in The Netherlands between 1991 and 2012

Abstract

Introduction

Population-based knowledge on the occurrence of specific injuries is essential for the allocation of health care services, optimization of preventive measures, and research purposes. Therefore, the aim of this study was to examine long-term nation-based trends in the incidence rate, trauma mechanism, hospital length of stay (HLOS), treatment, and outcome of hospital-admitted patients with an isolated tibia shaft fracture between 1991 and 2012 in The Netherlands.

Methods

All hospital-admitted patients in The Netherlands between 1991 and 2012 with an isolated tibia shaft fracture were included. Age and gender-standardized incidence rates were calculated for each year. Data were extracted from the National Medical Registration.

Results

The incidence rate for men decreased to 13.8/100,000 person years (py). For women the incidence rate remained stable with 7.2/100,000 py. Incidence showed a peak for adolescent men (15–19 years), and increased in both genders from 65 years onwards. Since 1993 the mean HLOS for isolated tibia fractures reduced from 10.8 to 5.4 days. Mean HLOS increased with age. Mean years lived with disability (YLD) was 4.5 years, declined linearly with age, and showed no gender effect.

Conclusions

In 22 years, the incidence rate of hospital admitted patients with an isolated tibia shaft fracture in The Netherlands dropped with 12%, which was mainly attributable to a 15% decline among men. Incidence rate, trauma mechanism, and HLOS were age and gender related. HLOS also reduced over time. Operation rate and YLD were only age related.

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The interhemispheric approach in children: our experience and review of the literature

Abstract

Objective

The interhemispheric approach (IA) has been extensively described for treating pathologies located at the lateral or third ventricle, pineal region, and periventricular locations. While these anatomical locations are the target of many pediatric pathologies, very few series have analyzed the morbidity and outcome of the IA in children. The aim of this study is to describe our experience using the IA in children, emphasizing the approach-related morbidity.

Methods

Twenty-six patients underwent 28 procedures using the IA between the years 2012 and 2016. Data for these patients was retrospectively analyzed. Surgical and approach-related morbidity were collected and analyzed.

Results

The mean age of the cohort was 10.1 ± 4.2 years and included 15 females (57.7%). Approach-related morbidity occurred following eight surgeries (28.6%; seven with anterior IA and one with posterior IA), including two pseudomeningoceles (7.1%), three persistent subdural effusions (10.7%), of which two were locally drained and one required subduro-peritoneal shunting, one epidural bleed (3.6%) which resolved spontaneously, and two infections (3.6%) treated with antibiotics. Cerebrospinal fluid leaks, supplementary motor area syndrome, seizures, and subdural hematomas did not occur in any of the patients. None of the approach-related complications led to permanent morbidity or to mortality.

Conclusion

The IA for lesions in and around the ventricular system is feasible and associated with a low permanent complication rate. When choosing this approach, the morbidity, although rarely permanent, should be considered.

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Geographic Distribution of Adult Inpatient Surgery Capability in the USA

Abstract

Introduction

Access to timely, quality, and affordable surgical services is an important component of health care systems. A better understanding of the geographic distribution of surgical services in the USA may help identify disparities in access to surgery.

Methods

Using the 2015 American Hospital Association Annual Survey, the 2010 Census Bureau Data, and the American Community Survey 5-year estimates from 2011 to 2016, all hospitals with surgical capabilities were geocoded with 30 straight-line mile service areas around each hospital using geospatial analysis. Major surgical hospitals were defined as meeting three of the four following criteria: bed size ≥ 45, ≥ 8600 operations per year, ≥ 12 operating rooms, and academic medical center. The distribution of the US population based on proximity to a hospital capable of performing adult inpatient surgery and a major surgical hospital was then analyzed and compared.

Results

Overall, 3409 hospitals were identified that had the capacity to perform adult inpatient surgery of which 1373 were defined as major surgical hospitals. Based on geospatial analysis, 10% of the US population was found to reside outside of a linear 30-mile radius of a surgical hospital. Younger age (OR 0.97, CI 0.96–0.97), female sex (OR 4.6, CI 4.3–5), African-American race (OR = 5.4, CI 4.7–6.2), Hispanic/Latino race (OR 5.5, CI 4.8–6.3), having completed high school or greater (OR = 3.6, CI 3–4.2), being employed (OR 4.8, CI 4.6–4.9), and having any type of health insurance were significantly associated with living in a service area.

Conclusion

A significant proportion of the US population lives greater than 30 straight-line miles from a major surgical hospital. Common demographic and socioeconomic factors highlight disparities in access to surgical care.

http://bit.ly/2C5thSY

Liver Resection for Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: a Multicenter Propensity Matching Analysis with HBV-HCC

Abstract

Background

The incidence of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Higher perioperative risks may be anticipated due to underlying steatohepatitis, while long-term outcomes after liver resection are unknown. We sought to investigate outcomes after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC using propensity score matching (PSM).

Methods

Consecutive patients who underwent liver resection for HCC between 2003 and 2014 were identified from a multicenter database. Patients with NAFLD-HCC were matched one-to-one to patients with HBV-HCC.

Results

Among 1483 patients identified, 96 (6.5%) had NAFLD-HCC and 1387 (93.5%) had HBV-HCC. Patients with NAFLD-HCC were older (median age 57 vs. 50 years), more often overweight (50.0% vs. 37.5%), less often to have cirrhosis (30.2% vs. 72.5%) and liver dysfunction (Child-Pugh B: 4.2% vs. 10.7%), had larger tumor size (median 7.2 vs. 6.2 cm) yet had better tumor differentiation (27.1% vs. 17.6%) compared with patients with HBV-HCC (all P < 0.05). Perioperative mortality and morbidity were comparable between the two groups (1.0% vs. 1.4% and 20.8% vs. 23.2%, both P > 0.05). No differences were noted in median OS and RFS among patient with NAFLD-HCC versus HBV-HCC before or after PSM.

Conclusion

While patients with NAFLD-HCC had different clinical characteristics than patients with HBV-HCC, liver resection resulted in similar perioperative outcomes and comparable OS and RFS among patients with NAFLD-HCC and HBV-HCC.

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Distinct Prognosis of High Versus Mid/Low Rectal Cancer: a Propensity Score–Matched Cohort Study

Abstract

Background

Rectal cancers have long been treated as a single-entity disease; however, whether the prognosis of high rectal cancer (inferior margin located 10.1 to 15.0 cm from the anal verge) differs from that of mid/low rectal cancer (0 to 10.0 cm) remains disputed.

Methods

Patients with stages I–III rectal adenocarcinomas undergoing curative-intent surgery were enrolled between 2007 and 2013 in this retrospective analysis. Exclusion criteria were neoadjuvant therapy or concurrent cancers. Propensity score matching and Cox regression analysis were performed to compare a 5-year overall and cancer-specific survival between patients with high and mid/low rectal cancer.

Results

Of 613 patients who met the inclusion criteria, 199 (32.5%) and 414 (67.5%) had high and mid/low rectal cancer, respectively. After propensity score matching (187 cases for each group), the high group showed a better overall survival (70.9 vs. 56.9%, p = 0.042) and cancer-specific survival (77.4 vs. 60.3%, p = 0.028) at 5 years compared with the mid/low group with stage III disease. However, high rectal cancer did not demonstrate prognostic superiority in stages I–II disease. Multivariate analysis identified high tumor location as an independent prognostic factor for cancer-specific survival (hazards ratio = 0.422, 95% confidence interval 0.226–0.786, p = 0.007) and overall survival (hazards ratio = 0.613, 95% confidence interval 0.379–0.991, p = 0.046).

Conclusions

Patients with stage III high rectal adenocarcinoma demonstrated better overall and cancer-specific survival than those with mid/low type, and tumor location was an independent prognostic factor for patients with rectal carcinomas.

http://bit.ly/2C6OewJ

Predictors of Hiatal Hernia Recurrence After Laparoscopic Anti-reflux Surgery with Hiatal Hernia Repair: a Prospective Database Analysis

Abstract

Background

The aim of this study is to identify factors that can predict hiatal hernia recurrence (HHR) in patients after anti-reflux surgery with hiatal hernia (HH) repair.

Methods

A single-institution, prospectively collected database was reviewed (January 2002–October 2015) with inclusion criteria of GERD and laparoscopic anti-reflux (AR) surgery with HH repair. Demographics, esophageal symptom scores, and pre- and post-upper gastrointestinal imaging (UGI) were collected. Mesh usage, HH type (sliding, paraesophageal (HH) or type IV), and size were evaluated, and patients who had HHR versus those who did not (NHHR) were compared. Statistical analysis was performed using IBM SPSS v.23.0.0, with α = 0.05.

Results

Three hundred twenty-two patients met inclusion criteria. Mean age was 56.9 ± 14.8 years (60.9% female), and mean follow-up was 19.9 ± 23.8 months. 88.2% underwent total fundoplication and 11.8% underwent partial fundoplication. HHR rate was 15.5%. HHR patients had larger HH than the NHHR group. There was no significant difference between groups for age, gender, BMI, race, and mesh usage. Only 3 patients (10.3%) with HHR reported mild-to-moderate heartburn, regurgitation, and solid or liquid dysphagia at 12-month follow-up. Overall reoperation rate was 1% in this population.

Conclusions

HHR is correlated with large hernia size. Mesh use and patient BMI were not predictors, and no correlation was identified between HHR and presence of GERD symptoms. Recurrence after repair is not uncommon, but is asymptomatic in most cases. Reoperation is rare and mesh is not routinely needed. Large asymptomatic HHs in the elderly often do not require intervention.

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The successful treatment of hepatocellular carcinoma arising from congenital hepatic fibrosis using radiofrequency ablation under laparoscopy

Abstract

Congenital hepatic fibrosis (CHF), a fibropolycystic disease, is characterized by bile duct malformation, periportal fibrosis, and renal polycystic disease. Although cholangiocellular carcinoma is the primary tumor arising from fibropolycystic diseases, hepatocellular carcinoma (HCC) is extremely rare. In addition, no algorism for determining the optimum HCC treatment has yet been available in cases of fibropolycystic disease due to variations in the background liver and renal conditions. We herein report a patient with HCC arising from CHF that was successfully treated using radiofrequency ablation (RFA) under laparoscopic assistance. A 37-year-old man with CHF was admitted to our hospital for treatment of HCC in 2014. Imaging revealed HCC located in hepatic segments II and VIII with diameters of 28 and 24 mm, respectively. There had been no histories of recurrent cholangitis or renal failure after when CHF was diagnosed in 2003. In addition, esophageal varices were well controlled. We achieved sufficient ablation using a bipolar ablation system without any complications. The post-operative course was uneventful, and the patient was free from HCC for 4 years. Thus, locoregional therapy, including RFA, is acceptable for the treatment of HCC arising from CHF when the background liver and kidney are preserved.

http://bit.ly/2Fga1GD

Herpes Infections and Dementia: Rebutting Alternative Fact

Abstract

Recent commentary in Neurotherapeutics by Nath critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment (AVT) against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer's disease (AD). Nath raises issues that we respond to: we point out that (i) the treated group (probably with severe infection) is likely to harbor genetic risk alleles that predispose to both AD and HSV infection—the potential treatment bias cited by Nath would support (rather than challenge) the preventive effect of AVT; (ii) HSV is well known to establish persistent infection in the brain; and (iii) current AVT compounds used to combat herpes viruses are highly specific for this class of viruses. Instead of "alternative fact," the findings of Tzeng et al. argue in favor of clinical trials of AVT in AD.

http://bit.ly/2FgR7yr