Inhibition associated with acetic acidinduced colitis throughout rodents by fresh Pediococcus acidilactici strains supplement makers retrieved from man gut microbiota

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After recovery, the pincer toenail deformity has been properly taken away. On the 1-year follow-up, recurrence wasn't seen and also the visual appeal of foot ended up being satisfactory. This kind of story surgical way is easy, minimises harm to the surrounding tissues, helps prevent wounding the particular nail blood flow and has couple of postoperative difficulties. © 2020 The actual Australasian School associated with Cosmetic dermatologists.Within human beings, histiocytic sarcoma (HS) is definitely an ambitious cancers concerning histiocytes. The rarity as well as heterogeneity explain in which treatment stays challenging. Expressing large clinical along with histopathological commonalities using human HS, the actual canine HS will be however frequent in distinct breeds thereby produces a unique natural style pertaining to man HS for you to understand the particular innate bases and also to investigate restorative options. We all identified sequence modifications in the particular MAPK path inside at the very least 63.9% (71/111) involving HS circumstances along with with each other distinctive BRAF (Zero.9%; 1/111), KRAS (6.2%; 8/111) and also PTPN11 (60.75%; 63/111) mutations concentrated with hot spots present with man types of cancer. Recurrent PTPN11 variations tend to be associated to deep disseminated HS subtype inside canines, the most intense medical business presentation. We then determined PTPN11 strains within 3/19 (Fifteen.7%) human HS people. Therefore, we propose PTPN11 versions as goals for a particular subset of man and also puppy HS your deep, stomach disseminated kind. Last but not least, simply by screening drugs individuals MAPK path within eight doggy HS cell collections, many of us identified an improved anti-proliferation task regarding MEK inhibitors when compared with PTPN11 inhibitors within canine HS neoplastic cellular material. When combined, these kind of final results illustrate the particular importance associated with naturally affected pet dogs inside deciphering anatomical mechanisms picking selleckchem productive precise therapies pertaining to this sort of rare and also aggressive cancers throughout people. © 2020 UICC.The HLA-B*44345N allele differs from HLA-B*44030101 with a Nineteen nucleotide erradication in opportunities 440 to be able to 458. © 2020 Steve Wiley & Son's A/S. Authored by John Wiley & Daughters Ltd.Qualifications The number of people undergoing autologous haematopoietic cellular implant (HCT) is growing, yet tiny is known about the elements which forecast adverse results. Reduced muscle mass and also unhealthy weight are generally associated with disability as well as premature fatality rate inside people who have non-malignant illnesses and might predict results following autologous HCT. METHODS This is any retrospective cohort review involving 320 patients that experienced autologous HCT with regard to Hodgkin as well as non-Hodgkin lymphoma among '09 along with This year. Sarcopenia skeletal muscle index male less then 43 cm/m2 [body mass index (BMI) less then 25 kg/m2 ] or less then 53 cm/m2 [BMI ≥ 25 kg/m2 ] and female less then 41 cm/m2 [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm2 (male), ≥396.4 cm2 (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regreuld inform targeted prevention strategies in patients at highest risk of complications after HCT. © 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.BACKGROUND Pancreatic cancer represents the third leading cause of US cancer deaths, with median survival less then 1 year. The goal of this study was to describe systemic treatments, healthcare utilization and costs, and overall survival among patients with unresectable/metastatic disease. METHODS This study used healthcare claims for commercial and Medicare Advantage enrollees diagnosed with pancreatic adenocarcinoma (at index date) during January 01 2010 to 31 May 2017. Included patients were aged ≥18 years, with continuous 6-month preindex enrollment. Patients were excluded by resectable disease, another primary cancer, or pregnancy. Cohorts were based on first-line (LOT1) chemotherapy regimen. RESULTS Overall, 12 978 patients (mean age 70 years, 51% male) were included, among which 5610 (43%) received chemotherapy. Of those, 23% received gemcitabine monotherapy, 22% gemcitabine-nab paclitaxel, 22% FOLFIRINOX, 3% FOLFOX, and 29% received other regimens. Mean LOT1 duration was 112 days; 60% did not undergo subsequent lines of therapy. Moreover, 50% of patients had an emergency room visit and 45% were hospitalized during LOT1. Among treated and untreated patients, mean total 6-month costs were $52 101. We found that patients receiving FOLFIRINOX had the highest costs, whereas those who received gemcitabine monotherapy had the lowest. Median overall survival (mOS) was 335 days with any first-line treatment. FOLFIRINOX-treated patients had the highest mOS (492 days), whereas gemcitabine monotherapy-treated patients had the lowest (223 days). CONCLUSIONS A large proportion (57%) of patients with unresectable/metastatic pancreatic cancer did not receive chemotherapy. Healthcare costs were higher for fluorouracil-based regimens, while lower for gemcitabine-based regimens. Survival rates were within expectations for advanced pancreatic cancer. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.OBJECTIVES This study investigates which oral diagnoses public primary dental care dentists record. METHODS An observational register-based retrospective follow-up study was performed in the public primary oral health care of a Finnish town after the dentists were advised to mark the diagnoses in their practices. The rate of recorded diagnoses resulting from visits to the public primary care dentists was studied. The assessed diagnoses were recorded with the 10th revision of the International Classification of Diseases. The distribution of diagnoses was recorded during a 2-year follow-up period. RESULTS The most frequent diagnosis groups were dental caries (K02, 38.6%), other diseases of dental hard tissues (K03, 14.9%), diseases of pulp and periapical tissues (K04, 11.4%), periodontal diseases (K05, 9.7%), and different types of bone fractures (S02, 8.1%). Periodontitis was underrepresented. CONCLUSIONS In public primary oral health care, there may be difficulties in adequate recording of certain chronic diseases. © 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.BACKGROUND Current clinical practices are shifting towards utilizing less invasive biopsy techniques, including fine needle aspiration (FNA) and needle core biopsies. If a patient has a suspected hematologic malignancy, a portion of the FNA sample is typically submitted for flow cytometry (FC) analysis, providing valuable immunophenotypic data. METHODS FNA specimens were identified via a pathology database search. All cases were morphologic evaluated and a subset of cases were analyzed by FC. RESULTS 245 hematologic FNA specimens were identified; 84% of these cases had an adequate number of cells for FC analysis, and an unequivocal morphologic diagnosis (benign or malignant) was rendered in 85%. The percentage of cases with an unequivocal diagnosis was statistically significantly higher in those with associated FC than with those without FC (90% vs 58%). Neither FNA technique nor anatomic site affected the likelihood of obtaining an adequate sample for FC analysis and/or rendering a definitive morphologic or unequivocal FC diagnosis. Likewise, tumor subtype did not affect the likelihood of acquiring enough cells for FC analysis, but occasionally resulted in equivocal FC diagnoses or discordant FNA and FC diagnoses. Aggressive B-cell lymphomas and Hodgkin lymphomas were significantly less likely to be detected by FC as compared to low-grade B-cell lymphomas. Discrepancies between FNA and FC diagnoses occurred in 13% of cases. The majority of discrepancies (78%) included FC false negatives, while only 22% of cases had atypical or positive FC with negative FNA. CONCLUSIONS FNA with associated FC is a powerful diagnostic technique; however, lymphoma subtype may affect diagnostic sensitivity by FC, and therefore, discordant FNA and FC results should be interpreted with caution. © 2020 Wiley Periodicals, Inc.The CCR5 molecule was reported in 1996 as the main HIV-1 co-receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV-1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the "renaissance of CCR5 research," this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases. © 2020 John Wiley & Sons Ltd.This research was carried out with the aim of comparing the effects of platelet-rich plasma (PRP) gel and gas dressing with serum physiologic applied to stage II pressure ulcer in coccyx of patients for 2 months on healing process and dressing costs. This prospective randomised controlled experimental study was conducted with 60 patients hospitalised in the palliative care unit after surgery. The experimental group (n = 30) was dressed with platelet-rich plasma gel. The control group (n = 30) was treated with serum physiologic dressing. At the end of the 20th observation of the patients in the experimental group, it was found that the mean scores of area, exudate, and tissue type in pressure sores decreased statistically (P  .05). The study showed that PRP gel had a positive effect on healing of stage II pressure ulcers with platelet-rich plasma gel dressings. In addition, when evaluated in the long term, it was concluded that platelet-rich plasma gel is easily accessible and less costly than serum physiological dressing. © 2020 Medicalhelplines.com Inc and John Wiley & Sons Ltd.Protein kinase A (PKA) activity is pivotal for proper functioning of the human heart, and its dysregulation has been implicated in a variety of cardiac pathologies. PKA regulatory subunit 1α (R1α, encoded by the PRKAR1A gene) is highly expressed in the heart, and controls PKA kinase activity by sequestering PKA catalytic subunits. Patients with PRKAR1A mutations are often diagnosed with Carney complex (CNC) in early adulthood, and may die later in life from cardiac complications such as heart failure. However, it remains unknown whether PRKAR1A deficiency interferes with normal heart development. Here, we showed that left ventricular mass was reduced in young CNC patients with PRKAR1A mutations or deletions. Cardiac-specific heterozygous ablation of PRKAR1A in mice increased cardiac PKA activity, and reduced heart weight and cardiomyocyte size without altering contractile function at 3 months of age. Silencing of PRKAR1A, or stimulation with the PKA activator forskolin completely abolished α1-adrenergic receptor-mediated cardiomyocyte hypertrophy. Mechanistically, depletion of PRKAR1A provoked PKA-dependent inactivating phosphorylation of Drp1 at S637, leading to impaired mitochondrial fission. Pharmacologic inhibition of Drp1 with Mdivi 1 diminished hypertrophic growth of cardiomyocytes. In conclusion, PRKAR1A deficiency suppresses cardiomyocyte hypertrophy and impedes heart growth, likely through inhibiting Drp1-mediated mitochondrial fission. These findings provide a potential novel mechanism for the cardiac manifestations associated with CNC. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.AIMS Aptamer BC 007, a 15-mer single-strand DNA oligonucleotide (5'-GGTTGGTGTGGTTGG-3'), was developed to neutralize functional autoantibodies that bind to the extracellular domains of G protein-coupled receptors (GPCR-AAB), leading to the modulation of receptor-mediated signalling cascades that induce pathophysiological states. Among the GPCR-AAB, there are those directed against the β1-adrenergic receptor (β1-AAB) that are highly present in patients with dilated cardiomyopathy (DCM) and are increasingly accepted as disease drivers. Using Doberman Pinschers (DP) with DCM, which possess similarities with human DCM among these β1-AAB positivity for that the disease-driving role in DP DCM was demonstrated, the safety of BC 007, efficacy for neutralizing β1-AAB, and the DP's outcome were investigated. METHODS AND RESULTS Fourteen client-owned β1-AAB-positive DP with electrocardiographically and echocardiographically indicated DCM were treated with BC 007. For controlling, two groups were created 14 β1-AAB-positi09) and Control group 2 (229 days, IQR 174-319 days; logrank P = 0.012). CONCLUSIONS Treatment with BC 007 for β1-AAB neutralization was safe, resulted in a long-lasting reduction of β1-AAB combined with improved cardiac function and prolonged the survival of DP with DCM. Using a natural large animal model of DCM considered superior to small animal models of immunization-induced cardiomyopathy, combined with a study design comparable with clinical trials, we believe that our results provide the basis for optimism that treatment with BC 007 might also be effective in human patients with DCM. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.BACKGROUND The population of dialysis patients is ageing. Dialysis nurses are confronted with geriatric patients with multiple comorbidities. Nurses are confronted with an increasing burden of care. OBJECTIVES The present study focused on the question of whether, over time, the increasing age and comorbidities of the haemodialysis population increased nursing care time. Furthermore, we studied potential changes in the predictors of the required nursing time. DESIGN Observational study. PARTICIPANTS A total of 980 dialysis patients from 12 dialysis centres were included. MEASUREMENTS Nurses filled out the classification tool for each patient and completed a form for reporting patient characteristics for groups of relevant haemodialysis patients at baseline and after 1 and four years. Changes in patient and dialysis characteristics were analysed, as well as the estimated nursing care time needed. RESULTS An increase in the nursing time needed for dialysis was largely due to decreased mobility, closing of the vascular access and a greater need for psychosocial attention and was most strongly present in incident dialysis patients. The time needed for dialysis decreased as patient participation increased and vascular access changed from catheters to fistulae. Over the four-year period, the average overall needed nursing care time per haemodialysis session did not change. CONCLUSIONS Our study shows that the average nursing time needed per patient did not change in the four-year observation period. However, more time is required for incident patients; thus, if a centre has high patient turnover, more nursing care time is needed. © 2020 European Dialysis and Transplant Nurses Association/European Renal Care Association.BACKGROUND Early rehabilitation has been shown to enhance functional outcomes. Whether the addition of virtual reality (VR) training could further improve muscle strength, mood state, and functional status for patients with acute stroke is unknown. AIMS To investigate the effectiveness of VR training on muscle strength, mood state (depression, anxiety), and functional status in patients following acute stroke. METHODS A randomized controlled trial was conducted. Patients with acute ischemic stroke (N = 152) were selected and randomly assigned with a 13 randomization ratio to either experimental group (EG) or comparison group (CG). Both groups received early rehabilitation. The EG received an extra 5 days of VR training (15 min of time, two times a day), started 24 hr to 3 days poststroke. Muscle strength, mood state, and functional status were collected at admission and at the day of discharge. Generalized estimating equations were applied to examine the intervention effects. RESULTS A total of 143 participanementation in clinical settings. © 2020 Sigma Theta Tau International.The detection and quantification of Legionella pneumophila (responsible for legionnaire's disease) in water samples can be achieved by various methods. However, the culture-based ISO 117312017, which is based on counts of colony-forming units per ml (CFU·ml-1 ) is still the gold standard for quantification of Legionella species (spp.). As a powerful alternative, we propose real-time monitoring of the growth of L. pneumophila using an isothermal microcalorimeter (IMC). Our results demonstrate that, depending on the initial concentration of L. pneumophila, detection times of 24-48 h can be reliably achieved. IMC may, therefore, be used as an early warning system for L. pneumophila contamination. By replacing only visual detection of growth by a thermal sensor, but otherwise maintaining the standardized protocol of the ISO 117312017, the new procedure could easily be incorporated into existing standards. The exact determination of the beginning of metabolic heat is often very difficult because at the beginning of the calorimetric signal the thermal stabilization and the metabolic heat development overlap. Here, we propose a new data evaluation based on the first derivation of the heat flow signal. The improved evaluation method can further reduce detection times and significantly increase the reliability of the IMC approach. © 2020 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.The new HLA-B*08253 allele characterized in Russian individuals. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.HLA-A*68227 differs from HLA-A*6884 by two single nucleotide substitutions in codon 10 and 90. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.We review the current state of mathematical modeling of cartilage pattern formation in vertebrate limbs. We place emphasis on several reaction-diffusion type models that have been proposed in the last few years. These models are grounded in more detailed knowledge of the relevant regulatory processes than previous ones but generally refer to different molecular aspects of these processes. Considering these models in light of comparative phylogenomics permits framing of hypotheses on the evolutionary order of appearance of the respective mechanisms and their roles in the fin-to-limb transition. This article is categorized under Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Mechanistic Models Developmental Biology > Developmental Processes in Health and Disease Analytical and Computational Methods > Analytical Methods. © 2020 Wiley Periodicals, Inc.We assessed prevalence of concurrently wasted and stunted (WaSt) and explored the overlaps between wasted, stunted, underweight and low mid-upper arm circumference (MUAC) among children aged 6-59 months in Karamoja, Uganda. We also determined optimal weight-for-age (WAZ) and MUAC thresholds for detecting WaSt. We conducted secondary data analysis with 2015-2018 Food Security and Nutrition Assessment (FSNA) cross-sectional survey datasets from Karamoja. Wasting, stunting and underweight were defined as less then -2.0 z-scores using WHO growth standards. Low MUAC was defined as less then 12.5 cm. We defined WaSt as concurrent wasting and stunting. Prevalence of WaSt was 4.96% (95% CI [4.64, 5.29]). WaSt was more prevalent in lean than harvest season (5.21% vs. 4.53%; p = .018). About half (53.92%) of WaSt children had low MUAC, and all were underweight. Younger children aged less then 36 months had more WaSt, particularly males. Males with WaSt had higher median MUAC than females (12.50 vs. 12.10 cm; p less then .001). A WAZ less then -2.60 threshold detected WaSt with excellent sensitivity (99.02%) and high specificity (90.71%). MUAC threshold less then 13.20 cm had good sensitivity (81.58%) and moderate specificity (76.15%) to detect WaSt. WaSt prevalence of 5% is a public health concern, given its high mortality risk. All children with WaSt were underweight and half had low MUAC. WAZ and MUAC could be useful tools for detecting WaSt. Prevalence monitoring and prospective studies on WAZ and MUAC cut-offs for WaSt detection are recommended. Future consideration to integrate WAZ into therapeutic feeding programmes is recommended to detect and treat WaSt children. © 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.Studies on bacterial physiology are incomplete without knowledge of the signalling and regulatory systems that a bacterium uses to sense and respond to its environment. Two-component systems (TCSs) are among the most prevalent bacterial signalling systems, and they control essential and secondary physiological processes; however, even in model organisms, we lack a complete understanding of the signals sensed, the phosphotransfer partners and the functions regulated by these systems. In this review, we discuss several tools to map the genes targeted by transcriptionally acting TCSs. Many of these tools have been used for studying individual TCSs across diverse species, but systematic approaches to delineate entire signalling networks have been very few. Since genome sequences and high-throughput technologies are now readily available, the methods presented here can be applied to characterize the entire DNA-binding TCS signalling network in any bacterial species and are especially useful for non-model environmental bacteria. © 2020 The Authors. Environmental Microbiology Reports published by Society for Applied Microbiology and John Wiley & Sons Ltd.Sustainable sources of energy have been identified as a possible way out of today's oil-dependency and are being rapidly developed. In contrast, storage of energy to a large extent still relies on heavy metals in batteries. Especially when built from biomass-derived organics, organic batteries are promising alternatives for truly sustainable energy storage. First described in 2008, research on biomass-derived electrodes has been taken up by a multitude of researchers worldwide. Nowadays, in principle electrodes in batteries could be composed of all kinds of carbonized and non-carbonized biomass On the one hand, all kinds of (waste) biomass may be carbonized and used in anodes of lithium or sodium ion batteries, cathodes in metal-sulfur or metal-oxygen batteries, or as conductive additive. On the other hand, a plethora of biomolecules like quinones, flavins, or carboxylates contain redox active groups that can be used as redox active component in electrodes with very little chemical modification. Biomass-based binders can replace toxic haloginated commercial binders enabling a truly sustainable future of energy storage devices. Besides the electrodes, also electrolytes and separators may be synthesized from biomass. Recent research progress in this rapidly emerging field is summarized with focus on potentially fully biowaste-derived batteries. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.In this mini-review, the importance and implementation of green chemistry practices in the pharmaceutical industry are illustrated. With specific examples, industrially most important organic transformations are highlighted along with their applications in the synthesis of drug molecules. A brief comparison between traditional unsustainable methods and modern green methods is made to shed light on the economic and environmental benefits of greener methods. In the end, green chemistry practices in the pharmaceutical industry of India and China are also discussed. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Although cognitive theory of mind (ToM) has been largely studied within neurodegenerative disorders including Alzheimer's disease (AD), studies focusing on affective ToM are relatively limited, yielding inconsistent findings. The current study aimed at investigating affective ToM abilities within different stages of AD (mild AD dementia [ADD], mild cognitive impairment [MCI], and subjective cognitive impairment [SCI]), together with its relationship with neuropsychological functioning. Eighty-one participants were tested with two different ToM tasks (Faux Pas Recognition Test [FPR] and Reading Mind in the Eyes Test [RMET]) and tests of attention, executive functions, episodic memory, and facial recognition. Our results showed two different affective ToM profiles in AD continuum while ADD group performed poorly on both tasks of ToM, MCI group displayed deteriorated performance on RMET but not on FPR. In addition, ToM performance was significantly related to episodic memory and verbal fluency within the overall sample. These findings suggest that impairment in the decoding process of emotional cues could begin even in the prodromal stage of AD. In contrast, the reasoning process of emotional information, as measured with FPR, could be preserved until the dementia stage. Moreover, the relation of affective ToM with amnestic functions and verbal abilities could provide evidence of a domain-general ToM impairment in AD. © 2020 The British Psychological Society.The advent of immune checkpoint inhibitors has improved survival in some types of cancer and brought promising prospects to cancer immunotherapy. Despite their clinical benefits, significant off-target toxicities resulting from the immune system activation have been observed, namely immune-related adverse events (irAEs), which pose to clinicians a new challenge of optimal management. With steroids being the mainstay of current management of irAEs, immunosuppressive agents are especially indicated for severe or steroid-refractory cases, based on current immunopathophysiological knowledge and on extrapolations of treatment options for primary autoimmune disorders. This review focuses on the status and recent clinical progress of immunosuppressive agents in the management of severe and steroid-refractory irAEs. © 2020 John Wiley & Sons Australia, Ltd.Three new indole diketopiperazine alkaloids, 11-methylneoechinulin E ( 1 ) and variecolorin M ( 2 ), and (+)-Variecolorin G ( 3a ), along with 12 known analogues ( 3b - 14 ), were isolated from a soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HRESIMS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of 3a and 3b were determined by experimental and quantum-chemical ECD investigations and single- crystal X-ray diffraction analysis. 3 is a pair of enantiomeric mixtures with a ratio of 12. Moreover, 9 is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI-H1975 gefitinib resistance (NCI-H1975/GR) cell lines were preliminarily evaluated by MTT method. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The degree by which metalloproteins partially regulate net charge ( Z ) upon electron transfer (ET) was recently measured for the first time using "protein charge ladders" of azurin, cytochrome c, and myoglobin [ Angew. Chem. Int. Ed. 2018, 57(19), 5364-5368]. Here, we show that Cu, Zn superoxide dismutase (SOD1) is unique among proteins in its ability to resist changes in net charge upon single ET (e.g., Δ Z ET(SOD1) = 0.05 ± 0.08 per electron, compared to Δ Z ET(Cytc) = 1.19 ± 0.02). This tight regulation of charge by SOD1 is attributed to the protonation of the bridging histidine upon copper reduction, yielding redox centers that are isoelectric at both oxidation states. Charge regulation by SOD1 would prevent the pK a of side-chains from being perturbed by ET at the redox center. Functionally, charge regulation would allow SOD1's "electrostatic loop" to attract superoxide equally regardless of redox state during the diffusion-limited reduction and oxidation of superoxide. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Temperature and nutrient availability, which are major drivers of consumer performance, are dramatically affected by global change. To date, there is no consensus on whether warming increases or decreases consumer needs for dietary carbon (C) relatively to phosphorus (P), thus hindering predictions of secondary production responses to global change. Here, we investigate how the dietary CP ratio optimising consumer growth (TERCP Threshold Elemental Ratio) changes along temperature gradients by combining a temperature-dependent TERCP model with growth experiments on Daphnia magna. Both lines of evidence show that the TERCP response to temperature is U-shaped. This shape indicates that consumer nutrient requirements can both increase or decrease with increasing temperature, thus reconciling previous contradictive observations into a common framework. This unified framework improves our capacity to forecast the combined effects of nutrient cycle and climatic alterations on invertebrate production. © 2020 John Wiley & Sons Ltd/CNRS.N-acetylcysteine (NAC) is a cystine prodrug shown to reduce cocaine- and cue-primed reinstatement of cocaine-seeking behavior in preclinical studies. In this inpatient study, the effects of NAC maintenance versus placebo on cocaine-seeking behavior were examined during cocaine-primed and unprimed self-administration sessions among non-treatment-seeking, cocaine-dependent individuals. Twelve participants completed this double-blind, placebo-controlled, within-subject crossover study. Each participant was maintained for 1 week (Sat-Fri) on NAC (1200-mg TID; 3600 mg/day total) and 1 week on placebo (0-mg TID); medication order was randomized. A subset of participants underwent proton magnetic resonance spectroscopy scans (n = 8) on the third day of medication (Mon) to assess neurochemistry in the rostral anterior cingulate (rACC; voxel = 4.5 cm3 ). In four randomized sessions (Tue-Fri) each week, each participant could earn unit amounts of cocaine (10 mg, fixed) versus money ($0.50 vs. $1.50) on a choice, progressive ratio schedule after insufflating active versus placebo cocaine-priming doses (110 mg vs. 4 mg). Relative to the placebo priming dose, the active cocaine priming dose (110 mg) increased cocaine-seeking behavior (p = .003). NAC reduced cocaine-primed cocaine-seeking behavior compared with placebo levels (p = .044) but did not alter placebo-primed cocaine-seeking behavior. The larger money alternative ($1.50) suppressed cocaine-seeking behavior relative to the smaller money alternative ($0.50; p = .011). Compared with placebo levels, NAC significantly decreased rACC glutamate + glutamine levels (p = .035) and numerically decreased rACC glutamate levels (p = .085). These preliminary findings indicate that NAC suppresses cocaine-seeking behavior in some, but not all, experimental scenarios. Further, our findings suggest NAC may exert its therapeutic effects by modulating excitatory tone in the rACC. © 2020 Society for the Study of Addiction.AIM Subjective happiness is an important marker of successful aging, and is associated with housing tenure status and household structure. However, the associations between subjective happiness and combinations of housing tenure status and household structure have not yet been clarified. Therefore, we examined which combinations of housing tenure status and household structure are associated with high or low subjective happiness among community-dwelling elderly people. METHODS Subjects were enrolled by stratified random sampling, and comprised of 1602 elderly persons aged ≥65 years as of January 2017 in Fukushima Prefecture, Japan. The subjects' data were collected via a self-completed questionnaire (effective response rate 53.4%), and the associations between subjective happiness and combinations of housing tenure status and household structure were analyzed by chi-squared test and logistic regression analysis, controlling the confounding variables such as care support needs, subjective economic status and health status. RESULTS The subjects reported significantly decreased subjective happiness when they were a renter living alone (odds ratio [OR] = 0.427 and 95% confidence interval [CI] = 0.249, 0.732) and with others (OR = 0.420 and 95% CI = 0.256, 0.687) after adjustment for confounding variables, compared with owner-occupier living with others (referent). CONCLUSIONS The results of the current study revealed significantly decreased subjective happiness when the subjects were renters regardless of household structure. Therefore, housing tenure status may be a stronger determinant of subjective happiness among community-dwelling elderly people than household structure. Geriatr Gerontol Int 2020; •• ••-••. © 2020 Japan Geriatrics Society.RATIONALE, AIMS, AND OBJECTIVES Poor adherence to evidence-based medications is a major problem in conventional clinical practise. Better prognostic tools are needed to identify those with the highest likelihood of being non-adherent. The objective of this study is to determine if a 2-item patient activation status (PAS) measure identifies Medicare beneficiaries at risk of poor adherence to drugs typically recommended in treating type 2 diabetes. METHODS PAS and medication adherence were assessed for respondents to the 2009 Medicare Current Beneficiary Survey and then compared using bivariate and multivariate tests. Participants' PAS was classified as "active," "high effort," "complacent," or "passive" based on how confident they were in identifying needed medical care and whether they brought medication lists to their doctors' visits. Adherence with oral antidiabetic drugs, angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers, and statins was assessed using proportion of days covered (PDC). RESULTS A total of 940 Medicare beneficiaries with diabetes enrolled in Part D plans in 2009. The overall effect of PAS on medication adherence was small (3% lower PDC for complacent/passive vs active/high effort beneficiaries, P  less then  0.10). However, interactions of complacent/passive PAS with other characteristics associated with poor adherence identified certain subgroups as especially prone to problematic adherence age  less then  65 (PDC -11%, P  less then  0.05), non-Hispanic black (PDC -13%, P  less then  0.05), and morbidly obese (-9%, P  less then  0.10). CONCLUSION A single question relating to taking medication lists to doctor visits may help identify patient subgroups prone to poor adherence in conventional practise, but larger samples are necessary to validate and extend these findings. © 2020 John Wiley & Sons, Ltd.RATIONALE, AIMS, AND OBJECTIVES The human body is regulated by intrinsic factors which follow a 24-hour biological clock. Implications of a circadian rhythm in the out-of-hospital cardiac arrest (OHCA) are studied but the literature is not consistent. The main objective of our study was to identify temporal cluster of high or low incidence of OHCA occurrence during a day. METHODS Multicentre comparative study based on the French national OHCA registry data between 2013 and 2017. After describing the population, the detection of significant temporal clusters of OHCA incidence was achieved using temporal scan statistics based on a Poisson model adjusted for age and gender. Then, comparisons between identified patients clusters and the rest of the population were performed. RESULTS During the study, 37 163 medical OHCA victims were included. The temporal scan revealed a significant 3-hour high incidence temporal cluster between 800 am and 1059 am (Relative R = 1.76, P  less then  .001). In the identified cluster, OHCA occurred more out of the home with fewer witnesses, and advanced life support was less attempted in the cluster. No difference was observed on the return of spontaneous circulation, survival at hospital admission, and survival 30 days after the OHCA or at hospital discharge. CONCLUSIONS We observed a three-hour morning high incidence peak of OHCA. This high incidence could be explained by different physiological changes in the morning. These changes are well known and the evidence of a morning peak of cardiovascular disease should enable medical teams to adapt care strategy and hospital organization. © 2020 John Wiley & Sons, Ltd.BACKGROUND Families of children with disabilities often face unique challenges. Developed in a U.S. context, the Beach Center Family Quality of Life measure assesses the effectiveness of supports and services that families receive. This study examines whether items from three sub-scales of the Beach Center instrument perform similarly for two samples, one from Lusaka, Zambia, and the second from a Midwestern U.S. state. METHODS This cross-sectional research used secondary data and completed hierarchical ordinal regression analyses on item-level performance within the sub-scales. RESULTS Only one item flagged for potential item bias with remaining items performing similarly when controlling for overall sub-scale scores. CONCLUSIONS This study extends existing research on the cultural and linguistic appropriateness of the Beach Center measure, providing additional validity evidence about the internal structure of the scales. Findings indicate that these items are acceptable outcome measures for policy and programme evaluations in Zambia. © 2020 John Wiley & Sons Ltd.BACKGROUND To assess (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania. METHODS Prostate cancer survivors ages ≥40 years were identified from the 2004-2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC-specific mortality. County-level data from the Pennsylvania BRFSS were used to estimate cancer-related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates. RESULTS There were 90 694 PCS ages 40-105 years (mean age = 66.19 years, SD = 9.25) included. Most were non-Hispanic white men (83%).