Fertility preservation practices among Ontario oncologists.
This study explores the attitudes, knowledge, and referring behaviors in fertility preservation among Ontario physicians providing adult cancer care. Ontario physicians with specialties in medical oncology, radiation oncology, gynaecologic oncology, and urology were invited to complete a 48-item questionnaire. A total of 152 questionnaires were available for analysis with a response rate of 23.7%. Seventy-four percent of the physicians indicated that they rarely or never modified cancer treatment due to concern about future fertility. Differences were found in fertility preservation knowledge among respondents in different medical specialties (p < 0.01) and clinical settings (p < 0.05). The frequency of initiating a referral was strongly associated with knowing where to refer patients (p < 0.001). The odds of knowing where to refer cancer patients was higher for physicians who work in a teaching hospital (p < 0.01) and a cancer centre (p < 0.01) compared with those who primarily work in a community setting. About 45% did not know where to refer female patients, and 69.7% rarely ever made a fertility preservation consultation referral for their female patients. The majority of respondents had positive attitudes despite their lack of current knowledge in cryopreservation services and fertility preservation options through assisted reproductive technologies. Our findings provide further insights of the relevance of considering physicians' medical backgrounds and practice settings when designing training modules to raise their awareness in fertility preservation issues.


Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways.
The melanocortin-3 receptor, MC3-R, is abundant in the brain and is activated by gamma-2-melanocyte stimulating hormone (gamma-2-MSH). We have previously reported the translocation of protein kinase C (PKC) in spontaneous hypertensive rat (SHR) brain synaptosomes treated with gamma-2-MSH. In this study, the expression of PKA and the related PKB in SHR brain synaptosomes was analyzed. PKA was detected in total synaptosomal fractions but not in particulate fractions, whereas PKB was not detected in either fraction. We next tested the hypothesis that the PKC pathway is involved in MC3-R signaling in a neuronal, CAD, cell line. Mobilization of intracellular Ca2+ was analyzed by dual fluorescence imaging of Fura-2AM loaded MC3-R transfected cells. An increase in intracellular Ca2+ was observed upon treatment with gamma-2-MSH. A MC3-R-green fluorescent protein (GFP) fusion protein was expressed and shown to localize mainly to the plasma membrane in the soma and to neurites in differentiated CAD cells. Treatment with gamma-2-MSH led to a punctate appearance and co-immunoprecipitation of the receptor fusion protein with protein kinase C-gamma (PKC-gamma). Differentiation of some neuronal cells has been shown to be associated with changes in the expression levels of protein kinase C isoenzymes. Induction of CAD cell differentiation was associated with down-regulation of the atypical PKC-zeta and protein kinase B (PKB/Akt1), that was less pronounced in MC3-R transfected cells. However, the levels of classical PKC isozymes, PKC-alpha, PKC-gamma, and PKC-beta were unchanged. These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation.


EMSY inhibits homologous recombination repair and the interferon response, promoting lung cancer immune evasion.
Non-small cell lung cancers (NSCLCs) harboring KEAP1 mutations are often resistant to immunotherapy. Here, we show that KEAP1 targets EMSY for ubiquitin-mediated degradation to regulate homologous recombination repair (HRR) and anti-tumor immunity. Loss of KEAP1 in NSCLC induces stabilization of EMSY, producing a BRCAness phenotype, i.e., HRR defects and sensitivity to PARP inhibitors. Defective HRR contributes to a high tumor mutational burden that, in turn, is expected to prompt an innate immune response. Notably, EMSY accumulation suppresses the type I interferon response and impairs innate immune signaling, fostering cancer immune evasion. Activation of the type I interferon response in the tumor microenvironment using a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of KEAP1-mutant tumors. Our results suggest that targeting PARP and STING pathways, individually or in combination, represents a therapeutic strategy in NSCLC patients harboring alterations in KEAP1.


Optical coherence tomography angiography analysis of microvascular abnormalities and vessel density in treatment-naïve eyes with diabetic macular edema.
The aim of this study was to evaluate the structural retinal vascular integrity using optical coherence tomography angiography (OCTA) in treatment-naïve eyes with diabetic macular edema (DME) and to compare it with findings in diabetic eyes without DME. In this prospective study, 70 eyes with diabetic retinopathy were included (37 eyes with DME and 33 eyes without DME). The medical records, including swept-source optical coherence tomography and 9 × 9 mm swept-source OCTA images were reviewed and compared between DME and non-DME groups. Microaneurysms, intraretinal microvascular abnormalities (IRMA), areas of capillary non perfusion, foveal avascular zone (FAZ), and capillary vascular density (CVD) were analyzed in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Compared to the non-DME eyes, DME eyes had more microaneurysms in the SCP and the DCP (p = 0,039 and p = 0,024 respectively), more IRMA in the SCP (p = 0,005), larger areas of capillary non perfusion in the SCP and the DCP (p = 0,026 and p = 0,02 respectively) and larger FAZ in both plexuses (p = 0,048 in the SCP and p = 0,012 in the DCP). The CVD in the DCP was lower in DME eyes compared to non-DME eyes (p = 0,007). The severity of DME was significantly correlated to the number of microaneurysms and to the FAZ surface. Central macular thickness was significantly correlated with the number of microaneurysms in the DCP, the surface of capillary non perfusion areas and the FAZ area in both plexuses. OCTA with a 9 × 9 mm field of view showed that the retinal vascular integrity regarding the number of microaneurysms, the number of IRMA, the surface of capillary non perfusion areas, the FAZ area and the CVD, was significantly more impaired in DME eyes compared to diabetic eyes without DME. The DCP seemed to be more affected in diabetic eyes with and without DME than the SCP.


Predictive ability, validity, and responsiveness of the multi-biomarker disease activity score in patients with rheumatoid arthritis initiating methotrexate.
We assessed the predictive value, validity, and responsiveness of the multi-biomarker disease activity (MBDA) score in rheumatoid arthritis (RA) patients initiating methotrexate. We examined data from a 16-week, open-label study of methotrexate in RA. Disease activity was assessed and the MBDA score was calculated using serum that was collected and banked from baseline and week 16. Multivariable logistic regression models assessed whether MBDA scores predicted treatment response. Pearson correlations assessed the convergent validity and external responsiveness of the MBDA score with other measures of RA disease activity. Internal responsiveness was assessed by calculating standardized response means (SRMs). A total of 130 patients initiated the study, with follow-up MBDA scores available on 95 patients. Baseline MBDA scores did not predict ACR response or achieving low disease activity. Higher baseline DAS28-ESR scores were significantly associated with an ACR20 response (odds ratio 1.89 per unit, 95% CI 1.20-2.96) but not ACR50, ACR70, or low disease activity. The MBDA score moderate-to-weakly correlated with the DAS28-ESR and ESR at baseline and week 16, with weak-to-very weak correlations with patient global and function. Change in MBDA scores moderately correlated with changes in DAS28-ESR and ESR, while weakly correlating with changes in patient global and function. The DAS28-ESR (SRM 1.31) demonstrated greater responsiveness following methotrexate treatment than the MBDA score (SRM 0.71). MBDA scores did not predict treatment response to methotrexate. The MBDA score weak-to-moderately correlated with baseline and post-treatment disease activity measures and was less responsive to methotrexate-related improvement than the DAS28-ESR.


X-chromosone-linked juvenile retinoschisis with hemorrhagic retinal cyst.
A 6-year-old boy with X-chromosome-linked juvenile retinoschisis had a large blood-filled retinal cyst surrounded by a rim of exudate which had infiltrated the macula. Spontaneous clearing of the blood and exudate was associated with improvement in vision.


BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.
Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.


Classification and functional characterization of spidroin genes in a wandering spider, Pardosa pseudoannulata.
Spiders impress us with their sophisticated use of silk and the stunningly distinct silk proteins (spidroins) in each spider species. Understanding how silks and spidroins function and evolve within the spider world is one profound interest to expand our knowledge on spider evolution. Spidroins are characterized with the divergent repeat core region flanked with the relatively conserved N- and C-terminus. The structure and number of the repeats contribute to the unique mechanical properties of the spidroin and the silk. Spidroins have been intensively studied in web-weaver spiders, but information regarding their diversity in wandering spiders remains scarce. Here, twenty spidroin genes were identified in the pond wolf spider, Pardosa pseudoannulata, belonging to the retrolateral tibial apophysis (RTA) clade. These spidroins were categorized into four classes, including twelve ampullate spidroin (AmpSp), four aciniform spidroin (AcSp), one tubuliform spidroin (TuSp), one pyriform spidroin (PiSp), and two spidroin-like proteins. Multiple copies of the AmpSp and AcSp genes were tandemly arranged in a cluster within the genome, and the N-terminal domains and repetitive sequences of the proximately located spidroins were highly similar, suggesting that the spidroin genes diversified via tandem duplication. Only four types of morphologically distinct silk glands were found in P. pseudoannulata, namely Ma, Mi, Ac, and Pi glands, consistent with the glandular affiliation hypothesis that spidroins co-evolved with glandular specialization to fit species-specific needs. Expression profiling revealed that the single tubuliform spidroin (TuSp) gene was highly expressed in gravid females and two AcSp genes displayed synchronous expression. Knock-down of the TuSp gene via RNAi resulted in fragile and cracked eggsacs and prolonged the female pre-oviposition period, validating its importance in spider reproduction. The genome-scale characterization and functional study of spidroin genes allows associating the presence of specific spidroins with silk utility in P. pseudoannulata and will expand our knowledge of spider evolution.


Chagas Disease Diagnostic Applications: Present Knowledge and Future Steps.
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stresses the necessity of developing new methods operational in point-of-care settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.


Matrix-assisted laser desorption/ionization mass spectra reflect solution-phase zinc finger peptide complexation.
The complexation between an 18-residue zinc finger peptide of CCHC type (CCHC = Cys-X2-Cys-X4-His-X4-Cys, X = variable amino acid) from the gag protein p55 of human immunodeficiency virus type 1 (HIV-1) and various transition metal ions was studied by means of circular dichroism spectroscopy and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). A correlation between the complexation behavior in solution and in MALDI-MS could be established. It was shown that MALDI-MS is a fast method suitable for studying metal binding properties of zinc finger complexes.


Characterization of carbonaceous aerosols over Delhi in Ganga basin: seasonal variability and possible sources.
The mass concentration of carbonaceous species, organic carbon (OC), and elemental carbon (EC) using a semicontinuous thermo-optical EC-OC analyzer, and black carbon (BC) using an Aethalometer were measured simultaneously at an urban mega city Delhi in Ganga basin from January 2011 to May 2012. The concentrations of OC, EC, and BC exhibit seasonal variability, and their concentrations were ∼2 times higher during winter (OC 38.1 ± 17.9 μg m(-3), EC 15.8 ± 7.3 μg m(-3), and BC 10.1 ± 5.3 μg m(-3)) compared to those in summer (OC 14.1 ± 4.3 μg m(-3), EC 7.5 ± 1.5 μg m(-3), and BC 4.9 ± 1.5 μg m(-3)). A significant correlation between OC and EC (R = 0.95, n = 232) indicate their common emission sources with relatively lower OC/EC ratio (range 1.0-3.6, mean 2.2 ± 0.5) suggests fossil fuel emission as a major source of carbonaceous aerosols over the station. On average, mass concentration of EC was found to be ∼38 % higher than BC during the study period. The measured absorption coefficient (babs) was significantly correlated with EC, suggesting EC as a major absorbing species in ambient aerosols at Delhi. Furthermore, the estimated mass absorption efficiency (σabs) values are similar during winter (5.0 ± 1.5 m(2) g(-1)) and summer (4.8 ± 2.8 m(2) g(-1)). Significantly high aerosol loading of carbonaceous species emphasize an urgent need to focus on air quality management and proper impact assessment on health perspective in these regions.


What Is the Preparedness and Capacity of Palliative Care Services in Middle-Eastern and North African Countries to Respond to COVID-19? A Rapid Survey.
Evidence from prior public health emergencies demonstrates palliative care's importance to manage symptoms, make advance care plans, and improve end-of-life outcomes. To evaluate the preparedness and capacity of palliative care services in the Middle-East and North Africa region to respond to the COVID-19 pandemic. A cross-sectional online survey was undertaken, with items addressing the WHO International Health Regulations. Nonprobabilistic sampling was used, and descriptive analyses were conducted. Responses from 43 services in 12 countries were analyzed. Half of respondents were doctors (53%), and services were predominantly hospital based (84%). All but one services had modified at least one procedure to respond to COVID-19. Do Not Resuscitate policies were modified by a third (30%) and unavailable for a fifth (23%). While handwashing facilities at points of entry were available (98%), a third had concerns over accessing disinfectant products (37%), soap (35%), or running water (33%). The majority had capacity to use technology to provide remote care (86%) and contact lists of patients and staff (93%), though only two-fifths had relatives' details (37%). Respondents reported high staff anxiety about becoming infected themselves (median score 8 on 1-10 scale), but only half of services had a stress management procedure (53%). Three-fifths had plans to support triaging COVID-19 patients (60%) and protocols to share (58%). Participating services have prepared to respond to COVID-19, but their capacity to respond may be limited by lack of staff support and resources. We propose recommendations to improve service preparedness and relieve unnecessary suffering.


Muscle variables of importance for physiological performance in competitive football.
To examine how match performance parameters in trained footballers relate to skeletal muscle parameters, sprint ability and intermittent exercise performance. 19 male elite football players completed an experimental game with physical performance determined by video analysis and exercise capacity assessed by intermittent Yo-Yo IR1 and IR2 tests, and a repeated sprint test (RST). Muscle tissue was obtained for analysis of metabolic enzyme maximal activity and key muscle protein expression. Total game distance, distance deficit from first to second half and high-intensity running in the final 15 min of the game were all correlated to the players' Yo-Yo IR1 performance (r = 0.55-0.87) and beta-hydroxyacyl-CoA-dehydrogenase (HAD) maximal activity (r = 0.55-0.65). Furthermore, platelet/endothelial cell adhesion molecule-1 (PECAM1) protein expression was weakly (r = 0.46) correlated to total game distance. Peak 5-min game distance faster than 21 km h(-1) was related to the Na(+)-K(+) ATPase subunit (α1, α2, β1 and FXYD1) protein levels (r = 0.54-0.70), while Yo-Yo IR2 performance explained 40 % of the variance in high-intensity game distance. Total and 1-min peak sprint distance correlated to myosin heavy chain II/I ratio (MHCII/I ratio) and sarcoendoplasmic reticulum Ca(2+) ATPase isoform-1 (SERCA1) protein (r = 0.56-0.86), while phosphofructokinase (PFK) maximal activity also correlated to total sprint distance (r = 0.46). The findings emphasize the complexity of parameters predicting physical football performance with Yo-Yo IR1 and HAD as the best predictors of total distance, while high expression of Na(+)-K(+) ATPase proteins and the Yo-Yo IR2 test are better predictors of high-intensity performance. Finally, sprint performance relates to skeletal muscle fiber-type composition.


Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium.
Brazilian folk medicine uses infusion of Costus spiralis leaf to help people to treat arterial hypertension and syndromes of cardiac hyperexcitability. Evaluate the aqueous fraction (AqF) effect on atrial contractility and investigate its mechanism of action. The AqF effect on the cardiac contractility was studied on isolated electrically driven guinea pig left atria. Atropine and tetraethylammonium (TEA) were employed to investigate whether potassium contributes for the inotropic mechanism of the AqF. The role of calcium in this effect was also studied. This was done by analysing the AqF effect on the Bowditch's phenomenon, as well as by studying whether it could interfere with the concentration-effect curve for CaCl(2), isoproterenol, and BAY K8644. Mice isolated cardiomyocytes were submitted to a whole-cell patch-clamp technique in order to evaluate whether the L-type calcium current participates on the AqF effect. Furthermore, the intracellular calcium transient was studied by confocal fluorescence microscopy. AqF depressed the atrial contractile force. It was the most potent fraction from C. spiralis leaf (EC(50)=305 ± 41 mg/l) (crude extract: EC(50)=712 ± 41; ethyl acetate: EC(50)=788 ± 121; chloroform: EC(50)=8,948 ± 1,346 mg/l). Sodium and potassium content in the AqF was 0.15 mM and 1.91 mM, respectively. Phytochemical analysis revealed phenols, tannins, flavones, xanthones, flavonoids, flavonols, flavononols, flavonones, and saponins. Experiments with atropine and TEA showed that potassium does not participate of the inotropic mechanism of AqF. However, this fraction decreased the force overshoot characteristic of the Bowditch's phenomenon, and shifted the concentration-response curve for CaCl(2) (EC(50) from 1.12 ± 0.07 to 7.23 ± 0.47 mM) indicating that calcium currents participate on its mechanism of action. Results obtained with isoproterenol (1-1,000 pM) and BAY K8644 (5-2000nM) showed that AqF abolished the inotropic effect of these substances. On cardiomyocytes, 48mg/l AqF reduced (∼23%) the L-type calcium current density from -6.3 ± 0.3 to -4.9 ± 0.2 A/F (n=5 cells, p<0.05) and reduced the intracellular calcium transient (∼20%, 4.7 ± 1.2 a.u., n=42 cells to 3.7 ± 1.00 a.u., n=35 cells, p<0.05). However, the decay time of the fluorescence was not changed (control: 860 ± 32 ms, n=42 cells; AqF: 876 ± 26 ms, n=35 cells, p>0.05). The AqF of C. spiralis leaf depresses myocardial contractility by reducing the L-type calcium current and by decreasing the intracellular calcium transient. Despite the lack of data on the therapeutic dose of AqF used in folk medicine, our results support, at least in part, the traditional use of this plant to treat cardiac disorders.


Two piperazic acid-containing cyclic hexapeptides from Streptomyces alboflavus 313.
Two novel cyclic hexapeptides, designated NW-G10 (1) and NW-G11 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their relative structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of several constituent amino acids were determined by Marfey's method. NW-G10 (1) and NW-G11 (2) exhibited significant activity against Gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), but they are not active against gram negatives.


The Stigma Resistance Scale: A multi-sample validation of a new instrument to assess mental illness stigma resistance.
Although associated with key recovery outcomes, stigma resistance remains under-studied largely due to limitations of existing measures. This study developed and validated a new measure of stigma resistance. Preliminary items, derived from qualitative interviews of people with lived experience, were pilot tested online with people self-reporting a mental illness diagnosis (n = 489). Best performing items were selected, and the refined measure was administered to an independent sample of people with mental illness at two state mental health consumer recovery conferences (n = 202). Confirmatory factor analyses (CFA) guided by theory were used to test item fit, correlations between the refined stigma resistance measure and theoretically relevant measures were examined for validity, and test-retest correlations of a subsample were examined for stability. CFA demonstrated strong fit for a 5-factor model. The final 20-item measure demonstrated good internal consistency for each of the 5 subscales, adequate test-retest reliability at 3 weeks, and strong construct validity (i.e., positive associations with quality of life, recovery, and self-efficacy, and negative associations with overall symptoms, defeatist beliefs, and self-stigma). The new measure offers a more reliable and nuanced assessment of stigma resistance. It may afford greater personalization of interventions targeting stigma resistance.


Screening of antimicrobials from Caribbean sea animals and isolation of bactericidal proteins from the littoral mollusk Cenchritis muricatus.
Marine organisms represent approximately half of the world's biodiversity by virtue of the sea being an immense reservoir of bioactive molecules. Here, antimicrobial crude extract activities of different marine invertebrates from the Caribbean Sea were evaluated. One of the most active, crude extracts was that marine snail Cenchritis muricatus, it was capable of totally inhibiting the development of Staphylococcus aureus and also showed a growth inhibition of 95.9% in Escherichia coli. Aiming to isolate molecules that confirm antimicrobial activity, the crude extract was purified by reversed-phase HPLC C-18 chromatography. Thereafter, one of the obtained fractions preserved this antibacterial activity. Furthermore, SDS-PAGE analysis (15%) showed the presence of two proteins of molecular masses with approximately 10 and 15 kDa, respectively. The first 19 amino acids of both proteins were sequenced by using Edman degradation, yielding unidentified primary structures compared against sequences deposited at NCBI databank. This is the first report of antibacterial proteins isolated from the mollusk Cenchritis muricatus and these proteins could be used as antibiotic alternatives in the aquacultural industry, as well as in agricultural or biomedical research.


Effective treatment of chronically progressive multiple sclerosis with low-dose cyclophosphamide with minor side-effects.
Twenty-one multiple sclerosis (MS) patients with a chronically progressive course were treated with a low dose of cyclophosphamide (CY). The control group consisted of 21 MS patients with a chronically progressive course who received the standard treatment (ACTH or cortisone). The control group consisted of patients who preferred the standard therapy because of its beneficial effects. In contrast, the patients of the CY group wanted to try a new therapy because the standard therapy was not effective. Thus before starting the study the progression of the disease was faster in the CY group than in the standard therapy group. As regards age, sex and degree of disability, the two groups were comparable. For 20 of the 21 patients in the CY group the degree of disability (Kurtzke scale) remained stable over 1 year; for 2 of the 20 stable patients there was even an improvement. In the standard therapy group, 7 out of 21 patients were stable over 1 year, while 14 showed progressive disability. A quantitative neurological score at the beginning and 1 year after the therapy showed a nearly identical difference between the CY group and the control group. The changes of the patients' abilities in daily-life activities (which were observed and recorded by the nurses) were similar to the Kurtzke scale data obtained by the physicians. The beneficial effect of CY in chronically progressive MS was thus highly significant (P less than 0.001). The side-effects of low-dose CY were fewer than those of ACTH.


Understanding the Physical Health Problems of People with Psychotic Disorders Using Digital Storytelling.
People with psychotic disorders struggle to be heard and express concerns beyond their mental health, especially concerns related to the side effects of treatment. Using digital storytelling, this study aimed to uncover and expose the underlying systems that oppress people with psychotic disorders from meeting their physical health needs. The stories revealed two themes: body as a contested site and biological entity with society, and (in)visible patient and paternalism. Spivak's theory of subalternity provided the theoretical basis for a critical analysis and discussion of the experiences. More research is required to highlight the power relations and structures that lead to health disparity in psychiatry.


Analytical methods for volatile compounds in wheat bread.
Bread aroma is one of the main requirements for its acceptance by consumers, since it is one of the first attributes perceived. Sensory analysis, crucial to be correlated with human perception, presents limitations and needs to be complemented with instrumental analysis. Gas chromatography coupled to mass spectrometry is usually selected as the technique to determine bread volatile compounds, although proton-transfer reaction mass spectrometry begins also to be used to monitor aroma processes. Solvent extraction, supercritical fluid extraction and headspace analysis are the main options for the sample treatment. The present review focuses on the different sample treatments and instrumental alternatives reported in the literature to analyse volatile compounds in wheat bread, providing advantages and limitations. Usual parameters employed in these analytical methods are also described.


The treatment outcome for adult patients with Ewing's sarcoma.
Ewing's sarcoma is the second most common bone malignancy in children, but is extremely rare in adults. The outcome of patients with localized disease has improved over the past decades due to better combination chemotherapies, and better methods of local control. Unfortunately, patients with metastatic disease have a very poor outcome with current antineoplastic therapies. In this article, we will review the primary treatment for adult patients with Ewing's sarcoma, both for localized and metastatic disease. The prognostic factors in adult patients with EWS will also be reviewed.


Health-related quality of life of long-term advanced melanoma survivors treated with anti-CTLA-4 immune checkpoint inhibition compared to matched controls.
Checkpoint inhibitors have changed overall survival for patients with advanced melanoma. However, there is a lack of data on health-related quality of life (HRQoL) of long-term advanced melanoma survivors, years after treatment. Therefore, we evaluated HRQoL in long-term advanced melanoma survivors and compared the study outcomes with matched controls without cancer. Ipilimumab-treated advanced melanoma survivors without evidence of disease and without subsequent systemic therapy for a minimum of two years following last administration of ipilimumab were eligible for this study. The European Organization for Research and Treatment of Cancer quality of life questionnaire Core 30 (EORTC QLQ-C30), the Multidimensional Fatigue Inventory (MFI), the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-Melanoma questionnaire (FACT-M) were administered. Controls were individually matched for age, gender, and educational status. Outcomes of survivors and controls were compared using generalized estimating equations, and differences were interpreted as clinically relevant according to published guidelines. A total of 89 survivors and 265 controls were analyzed in this study. After a median follow-up of 39 (range, 17-121) months, survivors scored significantly lower on physical (83.7 vs. 89.8, difference (diff) = -5.80, p=.005), role (83.5 vs. 90, diff = -5.97, p=.02), cognitive (83.7 vs. 91.9, diff = -8.05, p=.001), and social functioning (86.5 vs. 95.1, diff = -8.49, p= <.001) and had a higher symptom burden of fatigue (23.0 vs. 15.5, diff = 7.48, p=.004), dyspnea (13.3 vs. 6.7, diff = 6.47 p=.02), diarrhea (7.9 vs. 4.0, diff = 3.78, p=.04), and financial impact (10.5 vs. 2.5, diff = 8.07, p=.001) than matched controls. Group differences were indicated as clinically relevant. Compared to matched controls, long-term advanced melanoma survivors had overall worse functioning scores, more physical symptoms, and financial difficulties. These data may contribute to the development of appropriate survivorship care.


Sulfated exopolysaccharides from Porphyridium cruentum: A useful strategy to extend the shelf life of minced beef meat.
Sulfated exopolysaccharides (EPS) from Porphyridium cruentum strain were extracted and their antioxidant and anti-bacterial potentials were evaluated based on DPPH free radical, ABTS•+ radical cation and DNA nicking assays, and against four foodborne pathogenic bacteria, respectively. They showed also interesting functional, foaming and emulsion properties. Moreover, microbiological and chemical effects of EPS at 0.5, 1 and 2% on refrigerated minced beef meat were undertaken. Chemical analyses revealed that the treated meat underwent significant decrease (P < 0.05) of primary and secondary lipid oxidation. By the end of the storage period, exopolysaccharides at 2% reduced the metmyoglobin and carbonyl group accumulation compared to control samples and were more efficient (P < 0.05) against microflora proliferation. Furthermore, two multivariate exploratory techniques namely Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were applied successfully to all obtained data describing the main characteristics attributed to refrigerated meat samples. Overall, these findings indicated that EPS from P. cruentum are worthy being developed as functional and bioactive components for the meat industry.


Acetyl-11-keto-β-boswellic acid (AKBA) inhibits human gastric carcinoma growth through modulation of the Wnt/β-catenin signaling pathway.
Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, an active component of Boswellia serrata gum resin. We examined the effect of AKBA on human gastric carcinoma growth and explored the underlying molecular mechanisms. Inhibition of cancer cell growth was estimated by colorimetric and clonogenic assays. Cell cycle distribution was analyzed by flow cytometry and apoptosis determined using Annexin V-FITC/PI staining and DNA ladder quantification. After three weeks of oral AKBA administration in nude mice bearing cancer xenografts, animals were sacrificed and xenografts removed for TUNEL staining and western blot analysis. AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity. This effect might be associated with its roles in cell cycle arrest and apoptosis induction. The results also showed activation of p21(Waf1/Cip1) and p53 in mitochondria and increased cleaved caspase-9, caspase-3, and PARP and Bax/Bcl-2 ratio after AKBA treatment. Further analysis suggested that these effects might arise from AKBA's modulation of the aberrant Wnt/β-catenin signaling pathway. Upon AKBA treatment, β-catenin expression in nuclei was inhibited, and membrane β-catenin was activated. In the same sample, active GSK3β was increased and its non-active form decreased. Levels of cyclin D1, PCNA, survivin, c-Myc, MMP-2, and MMP-7, downstream targets of Wnt/β-catenin, were inhibited. AKBA effects on human gastric carcinoma growth were associated with its activity in modulating the Wnt/β-catenin signaling pathway. AKBA could be useful in the treatment of gastric cancers.


Multiple sclerosis: a survey of alternative hypotheses concerning aetiology, pathogenesis and predisposing factors.
There is abundant evidence that both environmental and genetic factors play a role in the aetiology and pathogenesis of multiple sclerosis. Currently, a virus infection and an abnormality of T-cell function are favoured candidates for the environmental and genetic factors, respectively. However, as long as convincing evidence for a specific viral infection and for a pathogenetic role for T-cells in multiple sclerosis is lacking, it may be worthwhile to consider alternative hypotheses that have been proposed in recent years. These have been classified in this review under the headings Toxins, Dietary and Metabolic Abnormalities, Embolism, Infection, and Immunological Mechanisms.


Statistical Challenges in the Analyses of Bone Mineral Density in Pediatric Populations.
Assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is standard in clinical practice with good precision and reproducibility. One way to analyze BMD data is through the Z-score where a subject's BMD is standardized against some reference population. This article highlights several potential problems in the calculation of the Z-score: (1) reference data are manufacturer dependent; (2) a transformation is recommended to reduce the skewness often seen in BMD data, however a transformation parameter is only available in some references using the Hologic manufacturer; (3) some reference data may be obsolete, as they were done under older scan models; (4) reference data are recommended to be interpolated to the subject's age, and linear interpolation is questionable; (5) reference data do not exist for all age groups; (6) reference data depend on the race of the subjects, and not all races are representative; and (7) reference data are limited to certain body composition. Given the limitation in the BMD Z-scores, other clinical symptoms (eg, bone fractures) or laboratory findings (eg, bone biomarkers) should be assessed in conjunction with the BMD Z-score to evaluate a subject's bone health.


The assembly and secretion of ApoB 100-containing lipoproteins in Hep G2 cells. ApoB 100 is cotranslationally integrated into lipoproteins.
The possibility that apoB 100 is cotranslationally translocated to the endoplasmic reticulum lumen and integrated into lipoproteins has been investigated. ApoB 100 nascent polypeptides were shown to be secreted from pulse-labeled Hep G2 cells after treatment with puromycin and chase for 1 or 2 h in the presence of puromycin and cycloheximide. These nascent polypeptides banded during sucrose gradient ultracentrifugation between the position of the high (HDL) and the low (LDL) density lipoproteins, revealing an inverse relationship between the length of the polypeptide and the density of the fraction. ApoB 100 occurred in the position of LDL and very low density lipoproteins (VLDL). Electronmicroscopy studies of the apoB-containing particles from the gradient indicated an increase in size with increasing length of the polypeptide. Furthermore, labeling studies indicated that the triglyceride load increased with the length of the polypeptide. An inverse relationship between the size of C-terminally truncated apoB polypeptides and the density of the assembled lipoproteins was also observed in experiments with transfected minigenes coding for apoB 41, apoB 29, and apoB 23. These proteins appeared on HDL particles. Pulse-chase experiments indicated that 80-200-kDa apoB nascent polypeptides on particles with HDL density, with time, were converted into larger polypeptides on lighter particles, to be fully replaced by apoB 100 on LDL-VLDL particles. The formation of these LDL-VLDL particles could be blocked by cycloheximide. Sixty-five percent of pulse-labeled apoB nascent polypeptides present in the microsomal fraction was released by sodium carbonate treatment, and 77% of these polypeptides could be recovered on the immature particles (banding between HDL and LDL) after sucrose gradient ultracentrifugation. Pulse-chase experiments indicated that these nascent polypeptides, on the immature lipoproteins, had the capacity to be precursors for all the apoB 100-containing LDL and VLDL particles formed in the cell. The obtained results indicate that a major portion of the apoB nascent polypeptides in the cell form lipoproteins cotranslationally during the translocation to the lumen of the endoplasmic reticulum.


HLA associations in South Asian multiple sclerosis.
Previous efforts to identify Human Leukocyte Antigen (HLA) gene associations with multiple sclerosis (MS) in the South Asian population have been underpowered. To identify the primary HLA class II alleles associated with MS in Indians. We typed HLA-DRB1, -DQA1 and -DQB1 in 419 patients and 451 unrelated controls by polymerase chain reaction using sequence specific oligonucleotide probes (PCR-SSOP). At the gene level DRB1 showed significant evidence of association (p=0.0000012), DQA1 showed only marginal evidence of association (p=0.04) and there was no evidence for association at DQB1 (p=0.26). At the DRB1 locus association is confirmed with the *15:01 (p=0.00002) and the *03 (p=0.00005) alleles. Our study confirms that the risk effects attributable to the HLA- DRB1*15:01and DRB1*03 alleles seen in Europeans are also seen in Indians. The absence of any evidence of association with DQB1 alleles reflects the lower linkage disequilibrium between DQB1 alleles and DRB1 risk alleles present in this population, and illustrates the potential value of fine mapping signals of association in different ethnic groups.


alpha-Tocopheryl succinate sensitizes established tumors to vaccination with nonmatured dendritic cells.
Dendritic cells (DCs) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness against established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors. In this study we have employed alpha-tocopheryl succinate (alpha-TOS), a nontoxic esterified analogue of vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine Lewis lung (3LL) carcinomas. We demonstrate that locally or systemically administered alpha-TOS in combination with nonmatured DCs injected intratumorally (i.t.) or subcutaneously (s.c.) significantly inhibits the growth of preestablished 10-day tumors (mean tumor volume of 77.5 +/- 17.8 mm3 on day 30 post-tumor injection) as compared to alpha-TOS alone (mean tumor volume of 471 +/- 68 mm3 on day 30 post-tumor injection). Additionally, the adjuvant effect of alpha-TOS was superior to that of cyclophosphamide (CTX). The mean tumor volume on day 28 post-tumor injection in mice treated with CTX+DCs was 611 +/- 94 mm3 as compared to 105 +/- 36 mm3 in mice treated with alpha-TOS+DCs. Analysis of purified T lymphocytes from mice treated with alpha-TOS+DC revealed significantly increased secretion of IFN-gamma as compared to T cells from the various control groups. This study demonstrates the potential usefulness of alpha-tocopheryl succinate, an agent nontoxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating established tumors.


The Effects of Contingent Caregiver Imitation of Infant Vocalizations: a Comparison of Multiple Caregivers.
The present study replicated and extended the Pelaez et al. (Journal of Applied Behavior Analysis 44:33-40, 2011) study, which examined the reinforcing effects of mothers' contingent imitation of their infants' vocalizations. Three infants aged 7-12 months who could vocalize sounds but not words participated with two caregivers for each infant (i.e., triads). During the intervention phase, the caregivers were asked to immediately imitate all vocalizations emitted by the child for a 3-min period. During the yoked control phase, the caregivers listened to an audio recording from the preceding condition and provided vocalizations non-contingently on the infants' responses. The procedures yielded different results across participants; one infant emitted a higher frequency of vocalizations during the contingent imitation phases over the control phases, and the other two infants showed higher rates of responding during the control phases. However, all infants emitted more imitative return vocalizations during contingent reinforcement conditions compared with the yoked control condition.


Most systematic reviews of adverse effects did not include unpublished data.
We sought to identify the proportion of systematic reviews of adverse effects which search for unpublished data and the success rates of identifying unpublished data for inclusion in a systematic review. Two reviewers independently screened all records published in 2014 in the Database of Abstracts of Reviews of Effects (DARE) for systematic reviews where the primary aim was to evaluate an adverse effect or effects. Data were extracted on the types of adverse effects and interventions evaluated, sources searched, how many unpublished studies were included, and source or type of unpublished data included. From 9,129 DARE abstracts, 348 met our inclusion criteria. Most of these reviews evaluated a drug intervention (237/348, 68%) with specified adverse effects (250/348, 72%). Over a third (136/348, 39%) of all the reviews searched, a specific source for unpublished data, such as conference abstracts or trial registries, and nearly half of these reviews (65/136, 48%) included unpublished data. An additional 13 reviews included unpublished data despite not searching specific sources for unpublished studies. Overall, 22% (78/348) of reviews included unpublished data/studies. Most reviews of adverse effects do not search specifically for unpublished data but, of those that do, nearly half are successful.


Augmentation of Positive Valence System-Focused Cognitive Behavioral Therapy by Inaudible High-Frequency Sounds for Anhedonia: A Trial Protocol for a Pilot Study.
Recent conceptualizations in Research Domain Criteria have indicated that anhedonia, 1 of 2 core symptoms of depression, which can be treatment resistant, is associated with deficits in the positive valence system, and inaudible high-frequency sound therapy has been shown to enhance reward-related brain circuitry. Hence, cognitive behavioral therapy focusing on the positive valence system enhanced with sound therapy could have a synergistic effect on anhedonia. To test the augmentation effect of inaudible high-frequency sounds on the efficacy of positive valence system-focused cognitive behavioral therapy to treat anhedonia. In this individual-level allocation, exploratory, single-center randomized superiority pilot trial, patients, therapists, and evaluators will be masked to intervention or placebo assignment. The trial will take place at a national psychiatric referral hospital in Tokyo, Japan, among 44 adult patients with clinically significant anhedonia and moderate to severe depression. Outcomes will be analyzed following the intent-to-treat principle using a repeated-measures mixed model. The intervention group will participate in 8 weekly sessions of positive valence system-focused cognitive behavioral therapy with in-session exposure to an inaudible high-frequency sound; the comparison group will undergo cognitive behavioral therapy with in-session exposure to a placebo sound. The primary outcome is anhedonia assessed using the self-reported Snaith-Hamilton Pleasure Scale. The secondary outcome is anhedonia assessed using the clinician-administered version of the Snaith-Hamilton Pleasure Scale. Recruitment for this study began in May 2018, and the projected date of final allocation is January 2020. A total of 21 eligible patients were registered for participation as of May 30, 2019. To date, treatments for depression do not guarantee clinically successful outcomes. This pilot trial will provide preliminary evidence of the augmentation effect of high-frequency inaudible sounds on cognitive behavioral therapy for anhedonia. Overall, exposure to an inaudible high-frequency sounds does not require attentional or cognitive effort from either patients or therapists; therefore, results from a future confirmative trial could indicate that cognitive behavioral therapy can be augmented in an effortless manner. umin.ac.jp/ctr Identifier: UMIN000031948.


Special Issue: Optical Characterizations of Novel Composite and Optically Active Materials.
Market pressures have placed new demands on modern photonic and opto-electronic materials, including requirements for miniaturization, higher efficiency, tunable and controllable optical and electrical properties, and consistent performance [...].


[Scattered arterioveinous fistulae of the lung associated with alcoholic cirrhosis : about one case complicated by neurological involvement (author's transl)].
We report case of 49 years old woman suffering from severe alcoholic cirrhosis and presenting arterioveinous fistulae of the lung which evidence was given by selective arteriography. Quantitative analysis of vasoactive intestinal polypeptide show no modification ; mecanism of the opening of fistulae could no be found. This observation is noteworthy in consideration of lung lasting evolution (4 years) and out come of neurological complication (must likely due to cortical phlebitis).


Northwest cancer specialists (ncs) cares: coordinated, advocacy, resources, education, and support: a palliative care program in an outpatient oncology practice.
A large community-based oncology practice developed a pilot project to enhance staff and patient awareness of the benefits of palliative care, advance care planning, and earlier intervention with patients with advancing disease. The results were ongoing implementation of palliative care conferences at all sites, greater numbers of referral to hospice, lessened chemotherapy given in the last 2 weeks of life, and the hiring of two social workers as a result of needs identified. Staff reported greater satisfaction with interprofessional communication.


[The effect of deep branches of cervical nerve on motorial function of trapezius muscle].
The aim of this study was to examine the effects of deep branches of cervical plexus on trapezius muscle. The evoked electromyography of 32 trapezius of 16 SD rats was examined in different time and results obtained were processed by statistical methods. After cutting the accessory nerves, stimulating the deep branches of cervical plexus evoked the myoelectricity, the myoelectricity results varied according to different time. The deep branches of cervical plexus are another important motorial supply to trapezius muscles. After cutting the accessory nerves, if the branches were undamaged, the shoulder's function would be greatly preserved.


Effect of dietary fats on linoleic acid metabolism. A radiolabel study in rats.
Effects on the linoleic acid metabolism in vivo of three dietary fats, rich in either oleic acid, trans fatty acids or alpha-linolenic acid, and all with the same linoleic acid content, were investigated in male Wistar rats. After 6 weeks of feeding, the rats were intubated with [1-14C]linoleic acid and [3H]oleic acid. The incorporation of these radiolabels into liver, heart and serum was investigated 2, 4, 8, 24 and 48 h after intubation. The amount of 14C-labelled arachidonic acid incorporated into the liver phospholipid of the group fed the oleic acid-rich diet was significantly higher than that of the other groups. However, compared to the trans fatty acids-containing diet, the oleic acid-rich diet induced only a slightly higher arachidonic acid level in the phospholipid fraction of the tissues as determined by GLC. Dietary alpha-linolenic acid more than halved the arachidonic acid levels. Our results do not support the hypothesis that the delta 6-desaturase system actually determines the polyunsaturated fatty acid levels in tissue lipids by regulating the amount of polyunsaturated fatty acids (e.g., arachidonic acid) synthesized. The biosynthesis of polyunsaturated fatty acids only is not sufficient to explain the complicated changes in fatty acid compositions as observed after feeding different dietary fats.


Investigation into the relationship between religious orientation and depression in elderly individuals.
In Turkey and around the world, the elderly population continues to grow, and society's expectations of this group have increased. At the same time, different research fields and studies have increasingly considered the effects of religious orientation on ageing. In this study, we examine the relationship between depression and religious orientation in the elderly. This descriptive study focused on determining the relationship between religious orientation and depression in the elderly. Data were collected by using a personal information form, the Religious Orientation Scale, and the 15-item Geriatric Depression Scale. Frequencies, percentages, means ± SD, Cronbach's α, and Pearson's correlation analysis were used to evaluate the data. More than half of the subjects (51.7%) were men, 61.9% were aged 65-74 years old, and 59.2% were married. For 35.2%, the highest level of education was primary school. Around half of the subjects perceived their income as moderate, and 57.4% received social security. With regard to depression, 72.5% of subjects were at risk, with the remaining 27.5% having no risk. There was a weak positive relationship between the mean ± SD scores on the Religious Orientation Scale (48.11 ± 6.36) and the 15-item Geriatric Depression Scale (8.23 ± 1.58; P < 0.01). This study found a relationship between religious orientation and a tendency towards depression in the elderly that increased with religious orientation.


Combinatorial treatment of CD95L and gemcitabine in pancreatic cancer cells induces apoptotic and RIP1-mediated necroptotic cell death network.
Combination therapy of cancer is based on the cumulative effects mediated by several drugs. Although molecular mechanisms of action of each particular drug are partially elucidated, understanding of the dynamic cross-talk between different cell death pathways at the quantitative level induced by combination therapy is still missing. Here, we exemplified this question for the death receptor (DR) networks in pancreatic cancer cells. We demonstrate that the combined action of CD95L and gemcitabine in pancreatic cancer cells leads to the simultaneous induction of caspase-dependent and caspase-independent cell death. The pro-apoptotic effects are mediated through down-regulation of the anti-apoptotic proteins c-FLIP and Mcl-1, while caspase-independent cell death was blocked by inhibition of the kinase activity of RIP1. Furthermore, gemcitabine co-treatment strongly increased the amount of cells undergoing CD95-induced RIP1-regulated necrosis. Imaging flow cytometry has enabled us to get the quantitative insights into the apoptosis-necroptosis network and reveal that the majority of the cells upon the CD95L/gemcitabine co-treatment undergoes necroptosis. Our data underlie the importance of the quantitative understanding of the interplay between different cell death modalities, which is essential for the development of anti-cancer therapies. Taken together, our results are important for combination therapy of pancreatic cancer comprising chemotherapeutics and DR-agonists and offer a possibility to sensitize cells with defects in the apoptotic machinery towards necroptosis-type-mediated death.


Case report: the unexpected culprit for multiple shunt revisions.
Silicone allergy in patients with ventricular shunts is uncommon hence easily missed. However, there are clinical features that could assist in identifying and diagnosing this condition. We discuss a case where a patient with a ventriculoperitoneal (VP) shunt presented to us with features suggestive of silicone allergy.


Comprehensive Study on the Reinforcement of Electrospun PHB Scaffolds with Composite Magnetic Fe3O4-rGO Fillers: Structure, Physico-Mechanical Properties, and Piezoelectric Response.
This is a comprehensive study on the reinforcement of electrospun poly(3-hydroxybutyrate) (PHB) scaffolds with a composite filler of magnetite-reduced graphene oxide (Fe3O4-rGO). The composite filler promoted the increase of average fiber diameters and decrease of the degree of crystallinity of hybrid scaffolds. The decrease in the fiber diameter enhanced the ductility and mechanical strength of scaffolds. The surface electric potential of PHB/Fe3O4-rGO composite scaffolds significantly increased with increasing fiber diameter owing to a greater number of polar functional groups. The changes in the microfiber diameter did not have any influence on effective piezoresponses of composite scaffolds. The Fe3O4-rGO filler imparted high saturation magnetization (6.67 ± 0.17 emu/g) to the scaffolds. Thus, magnetic PHB/Fe3O4-rGO composite scaffolds both preserve magnetic properties and provide a piezoresponse, whereas varying the fiber diameter offers control over ductility and surface electric potential.


Molecular dissection of subunit interfaces in the acetylcholine receptor. Identification of residues that determine agonist selectivity.
Agonists and antagonists select between the alphagamma and ns31744adelta binding sites of the fetal muscle acetylcholine receptor owing to different contributions by the gamma and delta subunits. To identify determinants of selectivity for agonists, we constructed a panel of gamma-delta subunit chimeras, co-expressed them with the alpha subunit in 293 HEK cells, and measured carbamylcholine binding affinity of intracellular complexes. Wild-type alphadelta complexes bind carbamylcholine about 30-fold more tightly than alphagamma complexes. This degree of selectivity is similar to that of the resting state of the receptor determined by kinetic analysis of single-channel events. We identify a primary set of determinants of selectivity, Lysgamma34/Serdelta36 and Phegamma172/Iledelta178, and a secondary set, Glugamma57/Aspdelta59 and Cysgamma115/Tyrdelta117. The contributions of all four determinants are subunit-dependent and are modified by interaction with one another. Coexpression of point mutant subunits with complementary wild-type subunits to form cell surface pentamers shows that Lysgamma34/Serdelta36 and Phegamma172/Iledelta178 contribute in a manner consistent with affecting selectivity of the resting state of the receptor, while Glugamma57 appears to contribute to the affinity of the desensitized state. The four determinants either coincide with or are close to residues known to contribute to the acetylcholine binding site. These results suggest that a minimum of four loops in the gamma and delta subunits contribute to the agonist binding site.


RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases.
Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT). Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival. One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052). RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.


Use of blood-free enrichment broth in the development of a rapid protocol to detect Campylobacter in twenty-five grams of chicken meat.
A Food Pathogen Enrichment (FPE) broth, which supports the growth of Campylobacter without lysed blood and CO2, was developed. The FPE broth supports the growth of Campylobacter to the same degree as Bolton and Preston broths. Using the FPE broth, we developed a novel rapid protocol to detect small numbers of Campylobacter in 25g of food. The sensitivity of FPE enrichment and PCR to detect Campylobacter spp. from spiked chicken meat was determined. The detection sensitivities for non-stressed C. jejuni and C. coli from fresh meat ranged from 5.8 to 1.1×10(1)CFU per 25g of chicken meat, and those for freeze-stressed C. jejuni and C. coli from frozen meat ranged from 9.9×10(1) to 2.0×10(2)CFU. The FPE broth enrichment culture (24h) of chicken meat, followed by PCR, resulted in a significantly higher detection score (80% positive) than conventional Bolton enrichment and subsequent colony isolation using mCCDA agar plates (18% positive). Differences between our new protocol and the Bolton enrichment method were due to the overgrowth of many resistant bacteria, especially extended-spectrum beta-lactamase-producing bacteria in the Bolton enrichment broth.


Comprehending dynamic protein methylation with mass spectrometry.
Protein methylation is a post-translational modification (PTM) which modulates cellular and biological processes including transcription, RNA processing, protein interactions and protein dynamics. Methylation, catalyzed by highly specific methyltransferase enzymes, occurs on several amino acids including arginine, lysine, histidine and dicarboxylic amino acids like glutamate. Mass spectrometry (MS)-based techniques continue to be the methods of choice for the study of protein PTMs. These approaches are powerful and sensitive tools that have been used to identify, quantify and characterize protein methylation. In addition, metabolic labeling strategies can be coupled to MS detection in order to measure dynamic and differential in vivo protein methylation rates. In this review, different applications of mass spectrometry technologies and methods to study protein methylation are discussed.


Rectal methohexitone induction in pediatric outpatients: physostigmine does not enhance recovery.
Rectal methohexitone (25 mg X kg-1) was used to induce anaesthesia in 15 unpremedicated children scheduled to undergo bilateral myringotomies as outpatients. Induction time ranged from 4 to 11 minutes. In the recovery room, all children received a slow intravenous injection of physostigmine (60 micrograms X kg-1), or saline in a double blind randomized fashion. The use of physostigmine did not significantly decrease the recovery room stay as compared to placebo (34 vs. 43 minutes). Vomiting and soiling were two side-effects associated with the use of physostigmine.


A rare cause of painful cervical swelling: myositis ossificans progressiva in childhood. Report of a case.
Myositis ossificans progressiva (MOP) is a rare condition of which we report a case in a 13-year-old girl with involvement of the cervical paraspinal and periscapular muscles. No ectopic ossifications were visible on plain radiographs. Computed tomography disclosed diffuse inflammation. Plain radiographs of the toes confirmed the diagnosis by visualizing characteristic bone abnormalities. Knowledge of the digital abnormalities seen in MOP is important to avoid unnecessary diagnostic investigations, most notably a surgical biopsy, which may trigger a flare of the disease. The prognosis is guarded.


Comprehensive evaluation of phenolic profile in dark chocolate and dark chocolate enriched with Sakura green tea leaves or turmeric powder.
Recently, a huge number of studies have confirmed the important role of chocolate polyphenols in human health, underlining its beneficial effects especially in the treatment of cardiovascular diseases. However, a thorough evaluation of chocolate phenolic profile is still lacking. This study aimed at a comprehensive characterization of dark chocolate phenolic profile, using non-targeted mass spectrometry identification. This approach allowed a tentative identification of 158 individual phenolic compounds: 67 were newly detected in dark chocolate, among these 38 were observed for the first time in chocolate as well as in cocoa beans or products. Ellagitannins, which have never been reported in cocoa or chocolate, represented about the 10% of the phenolic profile of dark chocolate. The enrichment of dark chocolate with Sakura green tea leaves or turmeric powder influenced and modified the phenolic profile, resulting in a phenolic concentration increase. In this way, this functional chocolate might maximize the beneficial effect of chocolate consumption, combining the positive health effects of chocolate, turmeric and green tea and, at the same time, reducing the amount of sugars and calories introduced with chocolate.


Preferential solvation of acridine in binary mixtures.
Preferential solvation studies of acridine have been investigated using optical absorption technique. The preferential solvation parameter shows that in dimethyl formamide (DMF)+ethanol mixture, the acridine is preferentially solvated by ethanol in DMF rich region and by DMF in ethanol rich region. In the case of DMF+Carbon tetrachloride mixture acridine is preferentially solvated by DMF.


Comparing heterogeneous SNOMED CT coding of clinical research concepts by examining normalized expressions.
A continual problem confronting the implementation of standardized vocabularies such as SNOMED CT is that their expressive flexibility and power provide more than one way to represent a given concept. The goal of this study was to investigate how the CliniClue Expression Transformer tool could be used to help in discerning similarities and differences among three separate sets of clinical research concepts coded in SNOMED CT by three different paid expert coding companies. Initial editing of the companies' coded datasets was required to enable accurate input into CliniClue Version: 2006.2.0030 Expression Transformer tool. The normal forms of the company codings for the 319 clinical research question/answer sets were compared to determine whether they were equivalent or otherwise related (e.g., if one was subsumed by the other). Basic frequencies were computed for (957) pairwise comparisons of each of 319 concepts each coded by the three expert coders, and the implications of the results discussed. The primary finding from this study was that, for each of the paired comparisons, approximately half of the time the companies' codings could be related, primarily via subsumption. The greatest percentage of equivalent concepts between any two companies was 33%. These same two companies also agreed most often on the core clinical concept measure from an earlier study by the authors. Heterogeneity among coders using the same controlled terminology appears inescapable despite the extensive efforts of terminological standards developers and implementers. In our study, the computable determination of equivalence of discordantly coded concepts still failed to yield acceptably comparable data. A clearer articulation, and perhaps a simplification, of rules for the consistent use for terminologies such as SNOMED CT is needed.


Iatrogenic vascular injury during peripheral revascularization.
Iatrogenic vascular injury may occur during peripheral revascularization procedures secondary to the application of vascular occlusive devices. This review summarizes the known mechanical causes of such injury, relates this to clamp design, and suggests methods to minimize such injury by appropriate selection and handling of vascular occlusive clamps.


The emerging role of biomarkers in atrial fibrillation.
Improved diagnostic techniques have identified various biomarkers that might play an important role in prediction of atrial fibrillation (AF) and related outcomes (cardio- and cerebrovascular events, and mortality and rhythm outcomes). Biomarkers can include blood markers (e.g., von Willebrand factor, D-dimer, natriuretic peptides, etc.), urine (e.g., proteinuria, estimated glomerular filtration rate, or creatinine clearance), cardiac imaging (echocardiography; transthoracic or transoesophageal), or cerebral imaging (e.g., computed tomography or magnetic resonance imaging), which can provide additional refinement to clinical stroke risk stratification for identification of "high risk" subjects. Although inclusion of some blood-based biomarkers (e.g., von Willebrand factor, D-dimer) in existing clinical stroke risk stratification schemes might improve their predictive value for identifying "high risk" patients, this concept might be outdated and overtaken by new developments in thromboprophylaxis (which now focus on initial identification of "low risk" patients who do not need any antithrombotic therapy, followed by patients with 1 or more stroke risk factors, to whom anticoagulation can be offered), and additional questionable practicality in "everyday" practice. Biomarkers could be applied as a "rule out" approach or as surrogates of anticoagulation efficacy in trials of new antithrombotic strategies. The present review aims to provide an update of the role of biomarkers in AF, with particular focus on AF outcomes.


Flexible biological arsenite oxidation utilizing NOx and O2 as alternative electron acceptors.
The feasibility of flexible microbial arsenite (AsIII) oxidation coupled with the reduction of different electron acceptors was investigated. The results indicated the acclimated microorganisms could oxidize AsIII with oxygen, nitrate and nitrite as the alternative electron acceptors. A series of batch tests were conducted to measure the kinetic parameters of AsIII oxidation and to evaluate the effects of environmental conditions including pH and temperature on the activity of biological AsIII oxidation dependent on different electron acceptors. Kinetic results showed that oxygen-dependent AsIII oxidation had the highest oxidation rate (0.59 mg As g-1 VSS min-1), followed by nitrate- (0.40 mg As g-1 VSS min-1) and nitrite-dependent AsIII oxidation (0.32 mg As g-1 VSS min-1). The kinetic data of aerobic AsIII oxidation were fitted well with the Monod kinetic model, while the Haldane substrate inhibition model was better applicable to describe the inhibition of anoxic AsIII oxidation. Both aerobic and anoxic AsIII oxidation performed the optimal activity at the near neutral pH. Besides, the optimal temperature for oxygen-, nitrate- and nitrite-dependent AsIII oxidation was 30 ± 1 °C, 40 ± 1 °C and 20 ± 1 °C, respectively.


Activated immune system in patients with Huntington's disease.
Abnormalities of immune system compartments were determined in 12 patients with Huntington's disease (eight males, four females; age 42.4+/-11.7 years) and 11 controls (7 males, 4 females; age 47.0+/-12.0). All patients were free from infectious diseases. Serum concentrations of a panel of serum soluble markers of immune activation were investigated, namely neopterin, 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R), interleukin-2-receptor (sIL-2R), kynurenine, tryptophan, immunoglobulins (Ig) A, M and G as well as routine laboratory tests. Compared to controls, we found significantly higher serum levels of IgA (p<0.01), sTNF-R, sIL-2R, neopterin, and complement component C3 (all p<0.05), and serum tryptophan was decreased (p<0.001). Higher concentrations of circulating immune complexes, cardiolipin antibodies, IgM, neopterin and lower tryptophan were associated with loss of cognitive function as assessed by the mini-mental-test. Five patients died within 1 year after measurements were performed. In these patients IgM, circulating immune complexes and neopterin concentrations were higher compared to survivors and serum tryptophan was lower. The data indicate an activation of various immune system compartments in Huntington's disease and that systemic immunological alterations might be important in the course of the disease.


Comfort and compressional characteristics of padding bandages.
Padding bandage is an essential component of the multi-layer compression system used for chronic venous management. Padding plays a critical role in managing pressure over bony prominences and ensuring uniform pressure distribution around the limb circumference. Moreover, it helps in the management of heat, moisture and body fluids or exudates during the course of treatment to provide comfort to the patients. To study the effect of structural and constructional parameters on the compressional (pressure absorption or distribution) and comfort (air, moisture and heat transmission) characteristics of the padding. This research focuses on the examination of polypropylene based nonwoven padding samples. Critical factors, i.e., fiber linear density, needling density and mass per unit area, have been chosen for this study to find their significance on the performance of padding. Simple laboratory based methods have been proposed to examine pressure reduction and comfort characteristics of the padding. Pressure absorption by the padding decreases with increase in mass per unit area and needling density of the padding. A padding composed of thicker fiber absorbs more pressure compared to padding made from thinner fiber. On examining comfort, it was found that the air and moisture vapor transmission increase with decrease in mass per unit area and needling density but have opposite effects with fiber linear density (p<0.01). The heat transmission decreases with increase in both mass per unit area and fiber linear density but has opposite effect for needling density. Padding composed of thick fiber with low mass per unit area and needling density could be more effective in pressure management and ensuring comfort. These results could be very useful for health practitioners, fabric engineers and manufactures to understand the significance of fibrous materials and their role in compression management, and could be further used as design consideration to optimized padding performance.


Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis?
Recurrent cellulitis following successful treatment is common and prevention should be a major component in the management of cellulitis. Conditions that increase the risk of recurrence include chronic edema, venous disease, dermatomycosis and obesity. These risk factors should be actively managed as further episodes of cellulitis increases the risk of recurrence. The role of non-antibiotic measures is important and should be first-line in prevention. Antibiotic prophylaxis is effective, but its role is limited to non-purulent cellulitis where risk factors are appropriately managed.


Evidence for glycoprotein components of the hepatocellular bile acid transporter.
The hepatocellular transporter, responsible for the uptake of bile acids and some foreign substances, can be shown to contain carbohydrate moieties. The hepatocellular uptake of cholate and phallotoxin is immediately inhibited by addition of wheat-germ agglutinin. Concanavalin A and lentil lectin reduce the uptake in a time-dependent manner. Apparently sialic acids or N-acetylglucosamine residues are involved in the translocation process. Polypeptides (Mr 50,000, 54,000) of the above transport system, identified by affinity labeling with [3H]isothiocyanatobenzamido cholate and [3H2]diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid, are heterogenously glycosylated. Binding of 80-90% of the 54, 50 kDa polypeptides to all immobilized lectins tested suggests that both high-mannose and complex type oligosaccharides with fucose and terminal sialic acid residues occur as carbohydrate chains. A 67 kDa labeled polypeptide is not glycosylated. Pilot experiments for purification of the above glycosylated membrane proteins on concanavalin A, lentil lectin and wheat-germ lectin columns are described. However, lectin affinity chromatography is not suitable as a one-step purification procedure for the labeled polypeptides.


Spatial organization of rat's behavior in a situation with three optional lever-pressing responses under continuous and fixed-interval schedules of food.
We assessed spatiotemporal distribution of behavior as a function of the spatial and temporal arrangement of food delivery. Eight food-deprived rats were exposed in an extended experimental chamber to a continuous reinforcement schedule (CRf) or to a fixed interval (FI) 30 s, with three levers contiguous to food dispenser or placed on separate panels. Responses on any of the levers were equally operative on the ongoing schedule. All rats moved mainly near to dispenser and levers when these were contiguous, under both, CRf and FI schedules, although distribution of responses on different levers was more variant under FI than under CRf. With separate levers, rats traveled through a larger area of the experimental space, especially under FI. Distribution of responses showed more variation under FI than under CRf schedule. Under FI, response patterns consisted in a post-meal pause followed by an acceleration towards the next food. Findings are discussed in the context of studies in which have been reported inconsistent patterns under FI schedules when are manipulated the number of operanda, dispensers, and their locations. It is highlighted the relevance of continuous analysis of rats' displacement, to account for the configuration of response patterns observed in this study.


Estimation of the general population and children under five years of age in France exposed to magnetic field from high or very high voltage power line using geographic information system and extrapolated field data.
The effects of extremely low-frequency magnetic fields, especially their long-term health effects, including childhood leukaemia, remain elusive. The International Agency for Research on Cancer has classified the exposure to magnetic fields >0.4 μT as 'possibly carcinogenic to humans (group 2 B)' for childhood leukaemia. However, the number of exposed individuals, particularly children, remains poorly documented in international literature. The objective of this study was to estimate the number of individuals living near a high or very high voltage line in France (≥63 kV), among the general population and children under the age of five years. The estimate considered different exposure scenarios depending on the line voltage and the distance of the housing from it, and whether the line is overhead or underground. The exposure scenarios were obtained using a multilevel linear model created from a measurement database published by "Réseau de transport d'électricité", the operator of the French electricity transmission network. Between 0.11% (n = 67,893) and 1.01% (n = 647,569) of the French population and between 0.10% (n = 4712) and 1.03% (n = 46,950) of children under five years of age were estimated to be living in an area potentially exposed to a magnetic field, depending on the exposure scenario (>0.4 μT and >0.1 μT, respectively). By making it possible to estimate the total number of residents, schools, and health institutions near high-voltage power lines, the proposed methodology can help identify potential co-exposures near high-voltage power lines, which are regularly cited as a possible explanation for contradictory results from epidemiological studies.


The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology, but exacerbates hypertriglyceridemia in rats with metabolic syndrome.
Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 wk of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis and diastolic dysfunction; attenuated adipose tissue inflammation and fibrosis; and alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis; attenuated the reduction in AMPK activity; upregulated sterol regulatory element-binding protein-1c gene expression; and increased the expression of microsomal triglyceride transfer protein gene in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters were affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.NEW & NOTEWORTHY Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. Inulin ameliorated hypertension, cardiac injury, and diastolic dysfunction without affecting obesity or insulin resistance in a rat model of metabolic syndrome. The favorable cardiac effects of inulin may be related to inhibition of systemic inflammation associated with a reduction in circulating interleukin-6 levels. Additionally, inulin exacerbated hypertriglyceridemia but alleviates adipose tissue and hepatic pathology in these animals, as well as increased the number of regulatory T cells in adipose tissue.


Lead and hyperactivity: lead levels among hyperactive children.
Previous work has demonstrated an association between hyperactivity and increased body lead burdens in school-age children. In the present study it is shown that within a group of hyperactive children those for whom an organic etiology is present have lead burdens lower than in those for whom no apparent cause could be found. These data lead us to reject the notion that hyperactivity per se is responsible for the acquisition of elevated lead levels, and further strengthen the suspicion that for some children lower lead level absorption may be implicated in the development of the hyperkinetic disorder.


Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.
In a model for mucosal mast cells (RBL-2H3 cells) a set H1-antagonist derived anti-allergic drugs containing a diphenylmethyl piperazinyl moiety was examined for their ability to inhibit release of the mediator beta-hexosaminidase. Cells were activated with antigen or the calcium ionophore A23187, whether or not in combination with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Oxatomide, hydroxyzine and cetirizine inhibit the antigen induced beta-hexosaminidase release. The release triggered by A23187, whether or not in combination with TPA is hardly influenced by the compounds. A biphasic dependence of the inhibition of exocytosis in RBL cells on lipophilicity is observed with the optimum at log P is 5-6. The extremely lipophilic compounds meclozine and buclizine are not active in this model. pH dependence of the effect of the drugs shows that especially the uncharged species are active in inhibiting exocytosis. The investigated compounds show an effect on phase transitions in L-alpha-phosphatidylcholine dipalmitoyl liposomes as assayed with differential scanning calorimetry (DSC). For the less extremely lipophilic compounds the induced changes in the phospholipid membranes increased with lipophilicity. The relation between structural features of the drug and the interaction with phospholipids is discussed in view of the DSC results. We conclude that location of the active drugs at the membrane or the membrane/protein interface is important for the inhibiting activity on exocytosis. This could affect several membrane related processes, which are abundant in the early phases of the IgE-mediated signal transduction process.


Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain.
Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.


A Multidimensional Model of Sexual Empowerment Among Young Black Men Who have Sex with Men: A Latent Profile Analysis.
Sexual empowerment is a key strategy in HIV prevention intervention design, yet its measurement has been conceptualized as homogeneous. To date, no studies have examined whether young Black men who have sex with men (YBMSM) exhibit heterogeneity across sexual empowerment. Using baseline data from a randomized controlled trial (N = 275, HIV-negative YBMSM), we classified YBMSM into sexual empowerment profiles based on five indicators using a latent profile analysis and assessed the associations between the sexual empowerment profiles and stigma-related experiences using multinomial logistic regression. Three profiles were identified: psychologically empowered with safer sex intentions (profile 1); psychologically disempowered with safer sex intentions (profile 2); and psychologically disempowered without safer sex intentions (profile 3). YBMSM reporting fewer stigma-related experiences were more likely to be profile 1 than profile 2 and profile 3. To empower YBMSM, interventions based on sexual empowerment profile targeting the psychological/behavioral aspects of empowerment and addressing stigma are needed.


Adaptation of the cyber aggression in relationships scale to Turkish: A validity and reliability study.
In this study, the cyber aggression in relationships scale (CARS) was intended to be adapted to Turkish. The study was designed as a methodological study with 426 students. The best fit index values for both the cyber perpetration and cyber victimization scales (CVSs) were obtained through confirmatory factor analysis. Cronbach's α internal consistency coefficients for the overall and sub-dimensions of the cyber perpetration scale and CVS were found to range from 0.88 to 0.92 and 0.85 to 0.91, respectively. In the study, CARS was found to be a valid and reliable instrument for Turkish society.


Quantifying the mycobiome and its major constituents on the skin of 20 normal dogs.
To report the density, and constituents, of the mycobiome on the skin surface of normal dogs. 20 normal dogs were recruited for this study, with informed consent in all cases. Flocked swabs were used to sample the skin surface and to sample the skin surface after superficial scraping with a blunted scapula. Both samples were taken within a brass guide with an internal area of 3.5 cm-2. Next-generation DNA sequencing was used to identify and quantify components of the mycobiome. The median density of the mycobiome was 1.1 X 105 cm-2 (IQR, 27,561, 409,572). Cladosporium spp and Vishniacozyma victoriae were found on all 20 dogs. Knowledge of the density and the composition of the cutaneous mycobiome will increase our understanding of skin biology and may have relevance to future therapeutic trials.


Tibiofemoral contact force differences between flat flexible and stable supportive walking shoes in people with varus-malaligned medial knee osteoarthritis: A randomized cross-over study.
To compare the effect of stable supportive to flat flexible walking shoes on medial tibiofemoral contact force (MTCF) in people with medial knee osteoarthritis and varus malalignment. This was a randomized cross-over study. Twenty-eight participants aged ≥50 years with medial knee osteoarthritis and varus malalignment were recruited from the community. Three-dimensional full-body motion, ground reaction forces and surface electromyograms from twelve lower-limb muscles were acquired during six speed-matched walking trials for flat flexible and stable supportive shoes, tested in random order. An electromyogram-informed neuromusculoskeletal model with subject-specific geometry estimated bodyweight (BW) normalized MTCF. Waveforms were analyzed using statistical parametric mapping with a repeated measures analysis of variance model. Peak MTCF, MTCF impulse and MTCF loading rates (discrete outcomes) were evaluated using a repeated measures multivariate analysis of variance model. Statistical parametric mapping showed lower MTCF in stable supportive compared to flat flexible shoes during 5-18% of stance phase (p = 0.001). For the discrete outcomes, peak MTCF and MTCF impulse were not different between the shoe styles. However, mean differences [95%CI] in loading impulse (-0.02 BW·s [-0.02, 0.01], p<0.001), mean loading rate (-1.42 BW·s-1 [-2.39, -0.45], p = 0.01) and max loading rate (-3.26 BW·s-1 [-5.94, -0.59], p = 0.02) indicated lower measure of loading in stable supportive shoes compared to flexible shoes. Stable supportive shoes reduced MTCF during loading stance and reduced loading impulse/rates compared to flat flexible shoes and therefore may be more suitable in people with medial knee osteoarthritis and varus malalignment. Australian and New Zealand Clinical Trials Registry (12619000622101).


Inhibition of epoxide hydrolase by valproic acid in epileptic patients receiving carbamazepine.
The effect of valproic acid (VPA) on the disposition of carbamazepine-10,11-epoxide (epoxide) was studied in five epileptic patients on chronic carbamazepine (CBZ) therapy. The individual pharmacokinetic parameters influencing epoxide disposition were determined in the presence and absence of VPA. VPA significantly decreased the clearance of unbound epoxide (an in vivo index of epoxide hydrolase activity), but did not appear to affect epoxide formation. VPA also increased the free concentrations of both CBZ and epoxide.


Avulsion fracture of the index metacarpal.
A case is reported of the avulsion of the insertion of Extensor Carpi Radialis Longus, an injury that has been reported only once before. The anatomy of the region and mechanism of injury are discussed, as is the importance of open reduction with internal fixation.


Effects of mindfulness meditation on mindfulness, mental well-being, and perceived stress.
The purpose of this study was to investigate the effects of mindfulness meditation using the Headspace™ app on mindfulness, mental well-being, and perceived stress in pharmacy students. Professional year one (P1), professional year two (P2,) and professional year 3 (P3) pharmacy students were recruited to participate. Students were instructed to meditate using the Headspace™ app for at least 10min per day for four weeks. Students at baseline completed the health promoting lifestyle profile (HPLP). Data was collected from the pre/post surveys using the Five Facet Mindfulness Questionnaire (FFMQ), Warwick-Edinburgh Mental Well-Being Scale (WEMWBS), and Cohen Perceived Stress Scale (PSS). Ninety-two pharmacy students enrolled in the study. Seventy-percent of the participants completed the study. Only one participant was excluded in the post data analysis due to non-adherence with the protocol. The data revealed that for all scales the intervention was associated with enhanced mindfulness and mental well-being and decreased perceived stress. Further analysis indicated that controlling for various health promoting lifestyle behaviors preserves the positive impact of mindfulness meditation as demonstrated. Mindfulness meditation uniformly and independently improved the participants overall mental health. The data supports a feasible option for minimizing stress and maintaining mental well-being in a demanding professional program. This study encourages students in pharmacy schools to adopt these practices in their curriculum.


Effects of nanoplastic on cell apoptosis and ion regulation in the gills of Macrobrachium nipponense.
Nanoplastic, ubiquitous in aquatic environments, are raising concern worldwide. However, studies on nanoplastic exposure and its effects on ion transport in aquatic organisms are limited. In this study, the juvenile oriental river shrimp, Macrobrachium nipponense, was exposed to five levels of nanoplastic concentrations (0, 5, 10, 20, 40 mg/L) in order to evaluate cell viability, ion content, ion transport, ATPase activity, and related gene expression. The results showed that the apoptosis rate was higher in the high concentration nanoplastic group (40 mg/L) compared to the low concentration nanoplastic group (5 mg/L) and the control group (0 mg/L). The ion content of sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+) showed a decreasing trend in gill tissue compared to the control group. The Na+K+-ATPase, V(H)-ATPase, Ca2+Mg2+-ATPase, and total ATPase activities in the gills of M. nipponense showed a general decrease with the increasement of nanoplastic concentration and time of exposure. When increasing nanoplastic concentration, the expression of ion transport-related genes in the gills of M. nipponense showed first rise then descend trend. As elucidated by the results, high nanoplastic concentrations have negative effect on cell viability, ion content, ion transport ATPase activity, and ion transport-related gene expression in the gills of M. nipponense. This research provides a theoretical foundation for the toxic effects of nanoplastic in aquaculture.


BRCA1 tumor suppressor network: focusing on its tail.
Germline mutations of the BRCA1 tumor suppressor gene are a major cause of familial breast and ovarian cancer. BRCA1 plays critical roles in the DNA damage response that regulates activities of multiple repair and checkpoint pathways for maintaining genome stability. The BRCT domains of BRCA1 constitute a phospho-peptide binding domain recognizing a phospho-SPxF motif (S, serine; P, proline; × varies; F, phenylalanine). The BRCT domains are frequently targeted by clinically important mutations and most of these mutations disrupt the binding surface of the BRCT domains to phosphorylated peptides. The BRCT domain and its capability to bind phosphorylated protein is required for the tumor suppressor function of BRCA1. Through its BRCT phospho-binding ability BRCA1 forms at least three mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1 and CTIP. The A, B and C complexes, at lease partially undertake BRCA1's role in mechanisms of cell cycle checkpoint and DNA repair that maintain genome stability, thus may play important roles in BRCA1's tumor suppressor function.


Transcatheter aortic valve implantation in acute decompensated aortic stenosis.
To assess the safety and efficacy of first-line transcatheter aortic valve implantation (TAVI) in patients presenting with acute decompensated aortic stenosis (ADAS). ADAS is common and is often treated medically or using balloon aortic valvuloplasty in the first instance. This temporizing measure results in suboptimal outcomes. In the current era, TAVI provides an alternative option. Consecutive patients who had either a TAVI for ADAS or electively were included in the study. The primary outcome was procedural and 30-day mortality and hospital length of stay (LOS). Secondary outcomes included 1-year mortality and procedural complications. Of note, 893 patients (mean age 83 ± 7, 50.5% male) underwent TAVI (19% ADAS, 81% elective). ADAS patients were more unwell with worse echocardiographic parameters than elective patients. ADAS patients of 55.9% were known to have significant aortic stenosis prior to their decompensation. Procedural mortality was not different between the ADAS and elective cohorts (1.2 vs. 0.7%; p = .62). The ADAS cohort had a higher 30-day mortality (5.3 vs. 1.1%; p = .002) and longer LOS (31.9 ± 20.7 days vs. 6.1 ± 6.5 days; p < .001). Multivariate analysis identified acute kidney injury and ADAS as significant predictors of 30-day mortality. TAVI for ADAS is safe and effective with procedural outcomes similar to elective patients. However, compared to elective patients, they have worse physiological baseline features, poorer prognosis at 30 days, and longer hospital admissions. Majority of patients who presented with ADAS were known to have AS prior to admission.