IL-34 was high in serum of women with polycystic ovary syndrome and may function as potential diagnostic biomarker and therapeutic target.
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in females of reproductive age, with a prevalence of 20%-33% in the general population. Interleukin (IL)-34 is a recently explored proinflammatory cytokine and is an important modulator in different disease types. However, the function of IL-34 in PCOS has yet to be investigated. The purpose of this study was to determine the IL-34 serum level in women with PCOS and to compare it to that of a relatively healthy control group. Focusing on its relationship with IL-6, TNF-α, and IL-1β and homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and low-density lipoprotein cholesterol (LDL-C). In this study, blood samples were obtained from 100 women with PCOS and 100 healthy control women for the purpose of estimating their serum levels of IL-34, IL-6, TNF-α, and IL-1β using the enzyme-linked immunosorbent assay technique. Serum levels of IL-34, IL-6, TNF-α, and IL-1β were all higher in PCOS women than in healthy controls, and the difference was highly statistically significant. Serum IL-34 concentration was positively correlated with IL-6, TNF-α, and IL-1β concentration. Additionally, serum concentrations of IL-34 were positively correlated with HOMA-IR, triglyceride, and LDL-C. When compared to normal women, IL-34, IL-6, TNF-α, and IL-1β levels were highly statistically significant in PCOS, and these high levels were associated with other cytokines (IL-6, TNF-α, and IL-1β), HOMA-IR, triglyceride, and LDL-C.


The Close Relationship Between Metabolic Syndrome and Hormone Receptor-Positive Early-Stage Breast Cancer.
The primary aim of the current study was to investigate the frequency of metabolic syndrome (MS) in early-stage breast cancer patients. Additionally, clinicopathological factors, such as anthropometric measurements and hormonotherapy, were examined for their roles as potential confounders of MS in these patients. In this retrospective cross-sectional study, all patients diagnosed with early breast cancer were included. Patients were divided into 2 groups with respect to MS diagnosis. Peripheral blood samples were obtained, clinical data were recorded, and body mass index (BMI) was calculated. The study was completed with a total of 207 patients of which 128 (61.8%) had MS. MS was more frequent hormone receptor positive subgroup and in recipients of adjuvant hormonotherapy. The comparison of patients with and without MS revealed significant differences in age, BMI and estrogen/progesterone receptor status. There were no significant differences between groups in terms of cancer stage, inflammatory markers, basal insulin and LDL levels, and tumor markers. MS appears to be rather widespread among women with early-stage breast cancer, and lifestyle changes, which can improve obesity-related adverse outcomes, should be more emphasized in clinical practice.


Discovery and Characterization of the Potent and Highly Selective 1,7-Naphthyridine-Based Inhibitors BAY-091 and BAY-297 of the Kinase PIP4K2A.
PIP4K2A is an insufficiently studied type II lipid kinase that catalyzes the conversion of phosphatidylinositol-5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI4,5P2). The involvement of PIP4K2A/B in cancer has been suggested, particularly in the context of p53 mutant/null tumors. PIP4K2A/B depletion has been shown to induce tumor growth inhibition, possibly due to hyperactivation of AKT and reactive oxygen species-mediated apoptosis. Herein, we report the identification of the novel potent and highly selective inhibitors BAY-091 and BAY-297 of the kinase PIP4K2A by high-throughput screening and subsequent structure-based optimization. Cellular target engagement of BAY-091 and BAY-297 was demonstrated using cellular thermal shift assay technology. However, inhibition of PIP4K2A with BAY-091 or BAY-297 did not translate into the hypothesized mode of action and antiproliferative activity in p53-deficient tumor cells. Therefore, BAY-091 and BAY-297 serve as valuable chemical probes to study PIP4K2A signaling and its involvement in pathophysiological conditions such as cancer.


Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection.
Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 μg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction. The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the bloodstream within 1-2 days after administration. In contrast, low amounts of p.hEPO were detected at 2-3 weeks after administration. These results suggest that the proposed method to detect gene doping can help obtain information for experiments using horses.


Spatio-temporal analysis of urban air pollutants throughout China during 2014-2019.
Air pollution control has become the top priority of China's "green development" concept since 2013. The Chinese government has enacted a range of policies and statutes to control contaminant emissions and improve air quality. On the basis of the national air quality ground observation database, the spatial and temporal distribution of air quality index value (AQI), fine particulate matter (PM2.5), coarse particles (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were explored in 336 cities throughout China from 2014 to 2019. AQI and most pollutants (except O3) decreased in concentrations from 2014 to 2019. In 2019, all cities except Henan reached the level 2 of the ambient air quality index, and six cities had a lower ambient air quality index and reached the level 1. Spatially, higher pollutant concentrations were concentrated in large city clusters, whereas the areas with high O3 concentration were found across the country. Furthermore, central heating was shown to have a negative impact on air quality. The observed AQI value, PM2.5, PM10, SO2, NO2, and CO concentrations were highest in north and northwest China and Henan province in central China. The correlations among pollutants suggest that the main sources of pollutants are fossil fuel combustion, industrial production, and motor vehicle emissions. The influence of meteorological factors on air quality, long-distance transportation, and the transformations of pollutants should be explored in future research. The online version contains supplementary material available at 10.1007/s11869-021-01043-5.


A multifactorial screening strategy to identify anti-idiotypic reagents for bioanalytical support of antibody therapeutics.
Antibodies are critical tools for protein bioanalysis; their quality and performance dictate the caliber and robustness of ligand binding assays. After immunization, polyclonal B cells generate a diverse antibody repertoire against constant and variable regions of the therapeutic antibody immunogen. Herein we describe a comprehensive and multifactorial screening strategy to eliminate undesirable constant region-specific antibodies and select for anti-idiotypic antibodies with specificity for the unique variable region. Application of this strategy is described for the therapeutic antibody Mab-A case study. Five different factors were evaluated to select a final antibody pair for the quantification of therapeutics in biological matrices: (i) matrix effect in preclinical and clinical matrices, (ii) assay sensitivity with lower limit of quantification goal of single-digit ng/ml (low pM) at a signal-to-background ratio greater than 5, (iii) epitope distinction or nonbridging antibody pair, (iv) competition with target and inhibitory capacity enabling measurement of free drug, and (v) neutralizing bioactivity using bioassay. The selected antibody pair demonstrated superior assay sensitivity with no or minimal matrix effect in common biological samples, recognized two distinct binding epitopes on the therapeutic antibody variable region, and featured inhibitory and neutralizing effects with respect to quantification of free drug levels.


Sex Differences of Combined Effects Between Hypertension and General or Central Obesity on Ischemic Stroke in a Middle-Aged and Elderly Population.
Hypertension and obesity are recognized as modifiable risk factors for stroke, but their combined effects are unknown. This study aimed to explore the combined effects of hypertension and general or central obesity on the risk of ischemic stroke in a middle-aged and elderly population. The data of 11,731 participants (53.5 ± 10.5 years old) were analyzed from the Northeast China Rural Cardiovascular Health Study, 2012-2013. General obesity (GO) was defined by body mass index (BMI); central obesity (CO) was measured by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR). The overall prevalence of ischemic stroke was 3.1%. After adjusting for age and sex, the odds ratios for having ischemic stroke were 4.31 (3.14-5.91) among subjects with hypertension, 1.79 (1.40-2.30) with GO, 1.94 (1.54-2.43), 1.98 (1.54-2.53), and 1.65 (1.33-2.06) with CO measured by WC, WHtR and WHpR, respectively. After full adjustment for potential confounders, the combinations of hypertension and obesity indices (including BMI, WC, WHtR and WHpR) were associated with the highest risk of ischemic stroke, especially in women, which were respectively 7.3-fold, 9.3-fold, 9.9-fold and 7.6-fold higher than that of individuals without both conditions. Our study results suggest that women with both hypertension and obesity, no matter defined by BMI, WC, WHtR or WHpR, were more likely to have ischemic stroke. A better understanding of the combined effects of these risk factors can help promote primary prevention in susceptible subgroups.


Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group.
To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m(2)) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles. OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) -free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters. Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.


Hemopoietic cell proliferation and death in the regenerating fetal rat liver.
The proliferation and death of hemopoietic cells in the regenerating liver of 17-day outbred albino rat fetuses were studied during 2 days after resection of 20% of the organ. The mitotic index of hemopoietic cells in the resected liver increased significantly 24 h after the operation in comparison with the control fetuses. No increase in the counts of apoptotic hemopoietic cells was detected in the regenerating liver. Hence, resection of 20% of the liver in rat fetuses stimulated the proliferation of hemopoietic cells and did not stimulate their apoptosis.


Gene Regulation Knows Its Boundaries.
The genome is folded nonrandomly inside the cell nucleus. How this contributes to gene regulation is an important subject of investigation. A new study by Despang et al. shows how the spatial segregation of genes and regulatory regions can influence developmental expression in subtle, but critical ways.


Nursing role in monitoring during cardiopulmonary resuscitation and in the peri-arrest period: a review.
The study objective was to present a comprehensive literature review on the monitoring of patients with cardiac arrest (CA) and the nursing contribution in this crucial situation. Monitoring techniques during cardiopulmonary resuscitation and in the peri-arrest period (just before or after CA) are included. Approaches used to access the research studies included a comprehensive search in relevant electronic databases (Medline, CINAHL, EMBASE, Cochrane Review, British Nursing Index) using relevant keywords (eg, cardiac arrest, resuscitation, monitoring, nurse, survival, outcome). Books and journals known to the authors were also used. The nurse's role in patients with CA is extremely significant and if performed correctly adds great insight to treatment planning and correct management. Early recognition of CA and invasive (methods and equipment that require endarterial or intravenous access) and noninvasive monitoring should be prompt and appropriate for early return of spontaneous circulation and improved neurologic outcome in patients.


Cardiac Surgery Exposure in General Surgery Residency-A Survey of General Surgery Residency Program Directors.
Little is known regarding how much exposure general surgery residents have to cardiac surgery, despite cardiothoracic (CT) surgery being an offered postresidency fellowship and career. Exposure to a subspecialty is important in shaping residents' interests and career decisions. A survey was sent to all general surgery program directors via the Association of Program Directors in Surgery examining cardiac surgery exposure during training. The survey examined the presence of operative rotations in cardiac surgery and cardiac critical care, portions of cases residents were permitted to perform, cardiac surgery mentorship and education, and perceived biases in applying to cardiac surgery. Differences between programs with and without cardiothoracic training programs were analyzed. In total, 44% (102/230) of program directors responded to the survey. Residents were involved in operative cardiac and cardiac ICU rotations in 61 programs (69.8%) and 39 programs (38.2%), respectively. Twenty programs (19.6%) had a dedicated cardiothoracic surgery training program and these programs had significantly more graduates who aspired to be cardiac surgeons (M = 2.75, SD = 2.47) compared to hospitals with no CT programs (M = 1.43, SD = 1.41; p = 0.031). 35.3% of program directors reported resident concern over family life. There is a notable heterogeneity in general surgery resident exposure to cardiac surgery, cardiac ICU, and cardiac surgery mentorship. Increased exposure, mentorship and mitigating resident concern over the impact of social factors on cardiac surgical careers should be key areas of focus to ensure continued encouragement of future trainees and surgeons.


Smart nano-in-microparticles to tackle bacterial infections in skin tissue engineering.
Chronic wounds (resulting from underlying disease, metabolic disorders, infections, trauma, and even tumours) pose significant health problems. In this work, microparticles, based on polysaccharides (maltodextrin or dextran) and amino acids, and doped with antibacterial nanoparticles (CuO or ZnO NPs) are designed. Smart nano-in-microparticles with a hierarchical 3D structure are developed. The ultimate goal aims at an innovative platform to achieve skin repair and to manage skin colonization by avoiding infection that could delay and even impair the healing process. The microparticles are prepared by spray-drying and cross-linked by heating, to obtain insoluble scaffolds able to facilitate cell proliferation in the wound bed. The nano-in-microparticles are characterized using a multidisciplinary approach: chemico-physical properties (SEM, SEM-EDX, size distribution, swelling and degradation properties, structural characterization - FTIR, XRPD, SAXS - mechanical properties, surface zeta potential) and preclinical properties (in vitro biocompatibility and whole-blood clotting properties, release studies and antimicrobial properties, and in vivo safety and efficacy on murine burn/excisional wound model) were assessed. The hierarchical 3D nano-in microparticles demonstrate to promote skin tissue repair in a preclinical study, indicating that this platform deserves particular attention and further investigation will promote the prototypes translation to clinics.


Smooth velocity fields for tracking climate change.
Describing the spatial velocity of climate change is essential to assessing the challenge of natural and human systems to follow its pace by adapting or migrating sufficiently fast. We propose a fully-determined approach, "MATCH", to calculate a realistic and continuous velocity field of any climate parameter, without the need for ad hoc assumptions. We apply this approach to the displacement of isotherms predicted by global and regional climate models between 1950 and 2100 under the IPCC-AR5 RCP 8.5 emission scenario, and show that it provides detailed velocity patterns especially at the regional scale. This method thus favors comparisons between models as well as the analysis of regional or local features. Furthermore, the trajectories obtained using the MATCH approach are less sensitive to inter-annual fluctuations and therefore allow us to introduce a trajectory regularity index, offering a quantitative perspective on the discussion of climate sinks and sources.


Therapeutic doses of recombinant factor VIIa in hemophilia generates thrombin in platelet-dependent and -independent mechanisms.
In hemophilia bypass therapy, a platelet-dependent mechanism is believed to be primarily responsible for recombinant factor VIIa (rFVIIa)'s hemostatic effect. rFVIIa may also possibly interact with other cells through its binding to endothelial cell protein C receptor (EPCR) or cell surface phospholipids. We aim to investigate the relative contribution of platelet-dependent and platelet-independent mechanisms in rFVIIa-mediated thrombin generation in hemophilic conditions at the injury site. Platelets were depleted in acquired and genetic hemophilia mice using anti-platelet antibodies. The mice were subjected to the saphenous vein injury, and the hemostatic effect of pharmacological concentrations of rFVIIa was evaluated by measuring thrombin generation at the injury site. Administration of anti-mouse CD42 antibodies to mice depleted platelets by more than 95%. As expected, hemophilia mice, compared with wild-type mice, generated only a small fraction of thrombin at the injury site. The depletion of platelets in hemophilia mice further reduced thrombin generation. However, when pharmacological doses of rFVIIa were administered to hemophilia mice, substantial amounts of thrombin were generated even in the platelet-depleted hemophilia mice. No differences in thrombin generation were detected among FVIII-/- , EPCR-deficient FVIII-/- , and EPCR-overexpressing FVIII-/- mice depleted of platelets or not. Evaluation of platelets by flow cytometry as well as immunoblot analysis showed no detectable expression of EPCR. Our data suggest that pharmacological concentrations of rFVIIa generate thrombin in hemophilia in both platelet-dependent and platelet-independent mechanisms.


Self-efficacy is associated with pain, functioning, and coping in patients with chronic temporomandibular disorder pain.
To examine the psychometric characteristics of a measure of self-efficacy for managing temporomandibular disorders (TMD) and to determine whether scores on this measure were related to pain, disability, and psychological distress in patients with chronic TMD pain. Patients seeking treatment for chronic TMD pain (n = 156, 87% female, mean age = 37 years) completed measures assessing pain, disability, mental health, pain-coping strategies, and self-efficacy for managing their pain. The self-efficacy measure, which was adapted from arthritis research, demonstrated good psychometric characteristics (Cronbach's alpha = 0.91, minimal floor and ceiling effects, and validity). Greater self-efficacy was associated with significantly (P < .05) lower levels of pain, disability, and psychological distress. Self-efficacy remained significantly associated with disability and mental health measures even after controlling for demographic variables and pain intensity. In addition, patients with higher self-efficacy reported significantly (P < .05) greater use of an active, adaptive chronic pain-coping strategy (task persistence) and less use of a passive, maladaptive chronic pain-coping strategy (rest). Self-efficacy for managing pain appears to be important in the adjustment of patients with chronic TMD pain. Research is needed to determine whether treatments designed to increase self-efficacy improve TMD patient outcomes.


Characterization of the toxicity of distamycin derivatives on cancer cell lines and rat heart.
The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer was at least three times lower than that of FCE 24561; on the same cell lines the IC50 of DXR was up to 14 and 240 times higher than that of FCE 24561 and FCE 24517, respectively. Isolated rat hearts perfused with concentrations of both derivatives equivalent to their respective IC50 values did not show any significant change in ECG parameters, contractility and coronary flow. Compared to control hearts, FCE 24517 10(-6) M induced a significant increase in PR interval, reduction in + dF/dtmax, heart rate and coronary flow, while FCE 24561 10(-6) M produced a modest but significant increase in S alpha T segment and decrease in + dF/dtmax. Rats treated with FCE 24561 3, 6 or 12 mg/kg, intravenously (i.v.), once weekly for 3 weeks had a modest increase in S alpha T segment and QRS complex duration, while a slight alteration of S alpha T segment and QRS complex duration were observed in rats given FCE 24517 1 or 2 mg/kg i.v. once weekly for 3 weeks. No cardiac histologic alterations were found in hearts from rats receiving FCE 24517 or FCE 24561. For comparison, the cardiotoxicity of doxorubicin (DXR) was evaluated in the same experimental models; perfusion of hearts with DXR 10(-6) M induced severe alterations in all parameters of the isolated hearts; the administration of DXR 3 mg/kg i.v. once a week for 3 weeks was associated with a widening of the S alpha T segment and QRS complex and cardiac histologic picture was markedly altered. In conclusion, distamycin A derivatives display elevated cytotoxicity while no substantial cardiotoxicity was observed.


Verapamil reduces the size of reperfused ischemically injured myocardium in hypertrophied rat hearts as assessed by magnetic resonance imaging.
Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify the extent of myocardial injury after a brief coronary occlusion and reperfusion in response to verapamil treatment in a rat model of left ventricular hypertrophy (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8 weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days, whereas group 2 (n = 13) received no therapy. Before MR examination was performed, each rat was subjected to 25 min of coronary artery occlusion followed by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at contiguous levels of the LV and used to estimate the size of the myocardial injury. The size of the infarcted region was demarcated at postmortem examination by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was administered, no significant difference in signal intensity was seen between nonischemic and reperfused ischemically injured myocardium. After gadoteridol was injected, a hyperintense zone indicative of myocardial injury was observed in 8 of 13 rats treated with verapamil and in all untreated animals. The size of the injury was significantly larger in untreated hearts than in hearts treated with verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was found between the two measurements. No significant difference in the size of jeopardy area was seen between the two groups as (defined by blue dye infusion). In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate the effects of therapies applied to reduce myocardial injury. Verapamil can cause reduction in the extent of ischemic injury after reperfusion of hypertrophied myocardium.


A novel coexistence of tetrasomy 8 and FLT3-ITD along with variant 3 way translocation t(4;17;15) in acute promyelocytic leukemia: Case study and literature review.
Here, we report a case of Acute promyelocytic leukemia (APL) with three way complex translocation involving chromosomes 4, 15, and 17. Although chromosome 4 is most commonly associated chromosome in three way translocation, present case is the first report with four novel co-existent findings of new break point region on chromosome 4, new cyclic mechanism with simultaneous breaks, presence of a co-existent tetrasomy 8 and FLT3 ITD positivity.; Comprehensive assessment highlight the utility of combining morphology, immunophenotyping, karyotyping, fluorescence in situ hybridization, and molecular studies for better characterization, optimal management of APL with a better understanding of the pathogenic mechanism and prognosis of the disease.


Comparison of facial proportions and anthropometric norms among Turkish young adults with different face types.
This study aimed to determine the prevalence of three different face types among Turkish young adults based on facial indices, to assess and compare the vertical and horizontal dimensions for each type, and to establish anthropometric norms for Turkish adults. A total of 173 healthy young adults (83 females and 90 males) 17 to 25 years of age were examined. Using anthropometric landmarks, 8 horizontal and 10 vertical direct measurements were made with a millimetric compass. Using facial indices, 59 of the 173 subjects were classified as euryprosopic, 49 as mesoprosopic, and 65 as leptoproposic. In the total evaluation of both groups, all the parameters were higher in the males except forehead heights 1 and 2. A comparison of face types in females and males separately showed no significant differences between the parameters. The data presented in this study may help plastic surgeons and orthodontists objectively determine the relationships between facial structures for different face types. Additionally, the facial anthropometric norms derived from this study may be useful in the treatment of Turkish patients.


Refuting the myth of a 'tsunami' of mental ill-health in populations affected by COVID-19: evidence that response to the pandemic is heterogeneous, not homogeneous.
The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population. The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics. Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories. A low-stable profile characterised by little-to-no psychological distress ('resilient' class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.


Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children.
Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as "normal" with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (>grade I), no single kidney and no difference in split renal function >20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months.


[Monomeric form of E. coli pyrophosphatase. Regulatory properties, stability and interaction with affinity inhibitors].
A comparative study on the E. coli inorganic pyrophosphatase subunit and native oligomer disclosed that the quaternary structure is not an essential prerequisite for exhibiting by the enzyme its regulatory properties. However, association of the subunits enhances the stability of the protein molecule and is obligatory for irreversible affinity inhibition.


Atomically thin Bi/Bi4Ti3O12 heterojunction mediated increasing active photogenerated carriers for boosting photocatalytic activity.
Two-dimensional (2D) semiconductors play an essential role in the field of photocatalytic repairing environment on account of their unique electronic structure and ultra-high specific surface area. Here, a 1-2-layer 2D ultrathin Bi/Bi4Ti3O12 (BTO-U-B2) heterojunction photocatalyst is constructed, and the delivery mechanism of electronic is proposed based on photoelectric performance and theoretical calculation results. The efficiency of separation, transfer and recombination of photogenerated carriers is considerably improved due to the enhanced internal electric field, shorter transfer distance and the introduction of electron traps, respectively. Moreover, bisphenol A (BPA) degradation rate of BTO-U-B2 heterojunction under xenon lamp is 9.06 and 2.57 times higher than that of Bi4Ti3O12 microplates and nanosheets, respectively. The enhanced photocatalytic activity benefits from the synergistic effect of 2D ultrathin structure and surface heterojunction. Additionally, the photocatalysis test are performed by replacing different environmental solutions and various organic pollutants, and results reveal that this heterojunction has a certain applicability. This work provides a deep insight into designing efficient 2D heterojunction photocatalysis.


Drug prescribing in renal failure.
Drug prescribing for patients with renal failure should incorporate adjustment of dosage regimens in order to avoid accumulation and thus adverse effects. Drugs usually eliminated by the kidneys require the most modification. Since immediate therapeutic efficacy is of importance, the initial or loading dose is essentially unaltered for patients with renal dysfunction. Maintenance doses can be adjusted by either lengthening the interval between doses of by reducing the size of individual doses. In clinical practice, a combination of both methods is used. Serum levels should be used as guides whenever possible. In interpreting these levels, recognition of decreased plasma protein binding and prolonged elimination half-lives in renal failure is imperative. In patients requiring dialysis, consideration must be given to adjustments for drug removal by the artificial membrane. Small molecules unbound to proteins are most easily removed. Specific guidelines for therapy with common drugs prescribed for patients with renal failure are given. These include: (1) narcotics and analgesics; (2) psychotherapeutic drugs; (3) cardiovascular drugs; and (4) antimicrobial agents.


Effect of oral nalmefene, an opiate-receptor antagonist, on meal-stimulated gastric acid secretion and serum gastrin concentration in man.
We evaluated whether nalmefene, an orally administered opiate-receptor antagonist, would inhibit gastric acid secretion in response to a meal in healthy humans. On separate days either 50 mg nalmefene or a placebo tablet was administered by mouth 90 min before a blenderized steak meal was infused into the stomach through a nasogastric tube. Compared to placebo, nalmefene inhibited meal-stimulated acid secretion in each of 6 subjects studied (P less than 0.05). During the second and third hours after the meal, nalmefene inhibited mean acid secretion by 16%. Nalmefene also resulted in significantly higher meal-stimulated serum gastrin concentrations than placebo (P less than 0.05) even though intragastric pH was kept constant at 5.0 in both experiments. These studies indicate that an orally administered opiate-receptor antagonist can inhibit gastric acid secretion in response to a meal in humans, yet increase meal-stimulated serum gastrin concentrations.


A critical opportunity: Detecting and Reducing Lead in Drinking Water at child care facilities.
There is no safe level of lead exposure. As exposure from point sources like lead paint have decreased, non-point sources such as drinking water have become a greater proportional source of total lead exposure. Even at low levels, lead exposure is shown to harm children, contributing to impaired development as well as learning and behavioral issues. This paper summarizes the key results of an Environmental Defense Fund (EDF) pilot study conducted at 11 child care facilities in 4 US states to evaluate approaches to testing and remediating lead in water at child care facilities. Over 75% of first draw samples contained lead levels under the 1 μg/L level recommended by the American Academy of Pediatrics (AAP). However, 10 of 11 child care facilities produced at least one sample above 1 μg/L. Fixture flushing, aerator cleaning, and fixture replacement were evaluated as remediation strategies. Fixture replacement was effective when initial lead was above 5 μg/L. Aerator cleaning did not have a measurable effect on lead levels for most fixtures but unexpectedly significantly increased lead levels in approximately 30% of fixtures. The 2021 Lead and Copper Rule (LCR) revision was applied to study data to determine whether updates would flag cases of low-level lead in child care settings and was found insufficient to prompt mitigation unless high lead was present at most taps.


A Geospatial database of gastric cancer patients and associated potential risk factors including lifestyle and air pollution.
Gastric cancer (GC) is a multifactorial disease and the fifth most frequent diagnosed cancer worldwide. It accounts for one third of cancer-related mortalities. Geospatial analysis using geographical information systems (GIS) can provide an efficient solution to identify spatial disparities associated with GC. As such, GIS enables policymakers to control cancer in a better way and identify the regions where interventions are needed. This study aims to publish a comprehensive dataset, which was applied to conduct a spatial analysis of GC patients in the city of Mashhad, Iran. We provide a personal geodatabase, a Microsoft Access database that can store, query, and manage both spatial and non-spatial data, which contains four feature classes. "Male_Stomach_Cancer_Patients" and "Female_Stomach_Cancer_Patients" are point feature classes, which show the age and geographical location of 1156 GC cancer patients diagnosed between 2014 and 2017. "Air_Polution_Mashhad" is another point feature class that reveals the amount of six air pollutants, which was taken from Mashhad Environmental Pollutants Monitoring Center between 2017 and 2018. Finally, "Stomach_Cancer_and_Risk_Factors" is a polygon feature class of neighborhood division of Mashhad, consisting of contributor risk factors including dietary habits, smoking, alcohol use, body mass index and population by age groups for all 165 city neighborhoods.


Humoral and cellular immune responses against SARS-CoV-2 variants of concern induced by heterologous CoronaVac/ChAdOx-1 versus homologous ChAdOx-1 vaccination in the elderly.
The concept of heterologous vaccination against SARS-CoV-2 infection has been adopted in Thailand with limited data on the induction of humoral and cellular immunity, particularly the CoronaVac/ChAdOx-1 (CoVac/ChAd) regimen in the elderly. In this study, the immune responses of the elderly induced by heterologous CoVac/ChAd and homologous ChAdOx-1 (ChAd/ChAd) vaccinations were demonstrated. A prospective observational study involving healthy participants aged ≥ 60 years who received heterologous CoVac/ChAd or homologous ChAd/ChAd vaccination was conducted. Surrogate neutralizing antibody (NAb) and T-cell responses against the SARS-CoV-2 wild type (WT) and variants of concern were determined at pre and post vaccinations. At 4 and 12 weeks after heterologous or homologous vaccination, the NAb levels against WT, Alpha, Beta, and Delta variants between each group were not significantly different, except for significant lower NAb against the Beta variant in heterologous group at 12 weeks after vaccination. The NAb against the Omicron at 4 weeks post-vaccination were below the cutoff level for antibody detection in both groups. However, higher spike-specific CD4 T cell producing IFN-γ and TNF-α in the heterologous than the homologous vaccination were observed. Insignificant difference of cellular immune responses to spike-peptides of Alpha, Beta, and Delta variants and their WT homologues was demonstrated. In the elderly, heterologous CoVac/ChAd vaccination could induce NAb response against the WT and non-Omicron variants not different from the homologous ChAd/ChAd vaccination. Both regimens could not give adequate NAb of the Omicron strain. The heterologous vaccination, however, induced higher spike-specific Th1 cell response.


Military Working Dogs: An Overview of Veterinary Care of These Formidable Assets.
For the clinician treating military working dogs, an understanding of how they are sourced, preventive medicine policies, and common disease conditions is paramount in optimizing the delivery of health care. Military personnel rely heavily on the availability of these K-9s, which bring a diverse array of capabilities to myriad operational settings. Anticipating and mitigating common diseases will ensure these dogs continue to serve the needs of US military and allied forces.


Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles.
Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.


Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation.
Some of the most widely used drugs, such as aspirin and penicillin, are covalent drugs. Covalent binding can improve potency, selectivity, and duration of the effects, but the intrinsic reactivity represents a potential liability and may result in idiosyncratic toxicity. For decades, the cons were believed to outweigh the pros, and covalent targeting was deprioritized in drug discovery. Recently, several covalent inhibitors have been approved for cancer treatment, thus rebooting the field. In this review, we briefly reflect on the history of selective covalent targeting, and provide a comprehensive overview of emerging developments from a chemical biology stand-point. Our discussion will reflect on efforts to validate irreversible covalent ligands, expand the scope of targets, and discover new ligands and warheads. We conclude with a brief commentary of remaining limitations and emerging opportunities in selective covalent targeting.


A novel, bedside, etiology specific prognostic model (Peds-HAV) in hepatitis A induced pediatric acute liver failure.
Hepatitis A virus (HAV) is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Our objective was to develop and validate a HAV-etiology specific prognostic model in PALF. All children with HAV induced PALF (IgM HAV reactive) were included. Outcome was defined at day 28. Only those with death or native liver survival were included. The model (Peds-HAV) was derived using the independent predictors of outcome and validated in a prospective independent cohort. Hepatitis A accounted for 131 (45.9%) of total 285 PALF. After excluding 11 children who underwent liver transplant, 120 children (74 survivors and 46 death) were included. The first 75 patients formed the derivation cohort and the next 45 patients formed the prospective validation cohort. In the derivation cohort, INR: OR 2.208, (95% CI 1.321-3.690), p = 0.003, grade of hepatic encephalopathy (HE): OR 3.078, (95% CI 1.017-9.312), p = 0.047 and jaundice-to-HE interval: OR 1.171, (95% CI 1.044-1.314), p = 0.007 were independent predictors of death. The final model comprised three criteria: (1) presence of grade 3-4 HE, (2) INR greater than 3.1, and (3) jaundice to HE interval more than 10 days. Presence of 2 or more of these criteria predicted death with 90% sensitivity, 81.4% specificity and 84.9% accuracy. Peds-HAV model was superior to existing prognostic models. In the validation cohort, Peds-HAV model predicted death with 83.3% sensitivity and 92.6% specificity. Peds-HAV model is a simple, bedside, dynamic, etiology (HAV) specific prognostic model based on 3 objective parameters with optimum sensitivity and specificity, hence should be used as liver transplant listing criteria in HAV induced PALF.


Furfuryl alcohol/tung oil matrix-based composites reinforced with bacterial cellulose fibres.
Polymeric materials have drastically changed the society in the last century. However, their non-renewable origin, together with their indiscriminate use and disposal, resulted in a huge accumulation of waste in the environment and raised a wide discussion about the emission of greenhouse gases, which must be considerably reduced to minimize global warming. Thus, the establishment of a consolidated production of polymers prioritizing the use of renewable sources of raw materials became a hot research topic. Vegetable oils are protagonists of this initiative, and their carbon-carbon double bonds are convenient reactive sites for chain growth polymerization reactions. However, typical vegetable oil-based homopolymers often do not display competitive thermo-mechanical properties, and the preparation of the corresponding copolymers and composites is therefore an interesting alternative strategy. Herein, the preparation of composites based on a tung oil/furfuryl alcohol co-continuous network reinforced with bacterial cellulose fibers is described. For this purpose, the cellulose nanofibers were suspended in furfuryl alcohol, and different amounts of the ensuing suspension were mixed with tung oil in the presence of trifluoroacetic acid as cationic initiator. Fourier-transform infrared spectroscopy analysis of all samples indicated the association of both tung oil and furfuryl alcohol in the final materials, with peaks belonging to cellulose superposed at the fingerprint regions of composites. Differential scanning calorimetry and thermogravimetry demonstrated an interesting relationship between the composition and the corresponding thermal properties, and the morphology of the materials was assessed by scanning electron microscopy (SEM), which revealed a homogeneous distribution of cellulosic fibers at lower concentrations. The results gathered here contribute to the development of original macromolecular materials exclusively based on the renewable platform.


A machine learning platform for the discovery of materials.
For photovoltaic materials, properties such as band gap [Formula: see text] are critical indicators of the material's suitability to perform a desired function. Calculating [Formula: see text] is often performed using Density Functional Theory (DFT) methods, although more accurate calculation are performed using methods such as the GW approximation. DFT software often used to compute electronic properties includes applications such as VASP, CRYSTAL, CASTEP or Quantum Espresso. Depending on the unit cell size and symmetry of the material, these calculations can be computationally expensive. In this study, we present a new machine learning platform for the accurate prediction of properties such as [Formula: see text] of a wide range of materials.


Skeletal stability and condylar position related to fixation method following mandibular setback with bilateral sagittal split ramus osteotomy.
To investigate postoperative intersegmental displacement and relapse following bilateral sagittal split ramus osteotomy (BSSRO) by comparing three different fixation methods: group A (sliding plate), group B (miniplate) and group C (bicortical screws). The present retrospective study included 55 patients with mandibular prognathism who were treated with BSSRO. To evaluate skeletal changes, cone-beam computed tomography was taken before surgery (T0), three days after surgery (T1), and 6 months after surgery (T2). Differences among the three groups were assessed using a one-way analysis of variance, where P < 0.05 was accepted as statistically significant. There were no significant differences among the three groups in demographic data and the amount of mandibular setback. In skeletal changes and condylar axis changes, there were no statistically significant differences among the three groups. However, there were statistically significant postoperative skeletal changes in group C (bicortical screws) at all landmarks. The mean horizontal relapse rate was 1.9% in group A (sliding plate); 4.8% in group B (miniplate); and 15.4% in group C (bicortical screws). The sliding plate system has good adaptability to the proximal segment after mandibular setback with BSSRO, and behaves according to semi-rigid fixation principles.


Are tattooing and body piercing indicators of risk-taking behaviours among high school students?
To date, studies pertaining to possible links between body modification and risk-taking behaviours have been conducted mainly among targeted groups. The objective of this study is to examine the influence of a number of risk-taking behaviours on the probability of being pierced or tattooed among a general adolescent population. Data come from a cross-sectional study conducted among a sample of 2180 students aged 12-18. Data were collected directly from students through a self-report survey. Findings confirm the "risky" nature of these practices even though the tattooed and pierced subjects of this study were from a general adolescent population. Factors that contribute significantly to the likelihood of teenagers being tattooed or pierced, for both genders, are associated with "externalized risk behaviours" such as multiple drug use, illegal activities, gang affiliation, problem gambling, school truancy and rave attendance. Nowadays, tattooing and body piercing are perceived by many as body decoration, increasingly belonging to the realm of generational conformity. Contrary to this view, our results suggest that these practices among adolescents are mostly adopted by those who are involved in various deviant or illegal activities, which are often interrelated.


Automated prescreening of pigmented skin lesions using standard cameras.
This paper describes a new method for classifying pigmented skin lesions as benign or malignant. The skin lesion images are acquired with standard cameras, and our method can be used in telemedicine by non-specialists. Each acquired image undergoes a sequence of processing steps, namely: (1) preprocessing, where shading effects are attenuated; (2) segmentation, where a 3-channel image representation is generated and later used to distinguish between lesion and healthy skin areas; (3) feature extraction, where a quantitative representation for the lesion area is generated; and (4) lesion classification, producing an estimate if the lesion is benign or malignant (melanoma). Our method was tested on two publicly available datasets of pigmented skin lesion images. The preliminary experimental results are promising, and suggest that our method can achieve a classification accuracy of 96.71%, which is significantly better than the accuracy of comparable methods available in the literature.


Unanticipated hemothorax during general anesthesia.
We experienced a case of uncommon spontaneous hemothorax during general anesthesia. A 72-year-old woman underwent emergency repair of damaged ascending colon. Her chest roentgenogram before surgery revealed no abnormalities. After the uneventful surgery, the trachea was extubated and the patient breathed without difficulty with stable vital signs. However, the S(p)(O)(2) varied around 95% with a 100% oxygen mask. Chest roentgenogram obtained after extubation showed a massive amount of fluid in the pleural cavity. A chest drainage tube was inserted, and approximately 1000 ml of frank blood was drawn without air leakage. Thereafter, her oxygenation remarkably improved. We could not determine the etiology of the hemothorax.


Cocaine abuse among heroin addicts in Spain.
Abuse of cocaine is becoming a major problem among heroin addicts in Spain. Between 1987 and 1988, 75% of patients admitted as inpatients for detoxification from opiate dependence had consumed cocaine during the 6 months prior to admission and 25% had abused cocaine daily or several times/week. These cocaine abusers showed more toxicologic and psychopathologic problems than opiate addicts who did not abuse cocaine. The opiate addicts who also abused cocaine had begun using illicit drugs earlier and showed a higher frequency of anti-HIV antibodies. They also had more antisocial personality disorders and persistence of depressive symptoms during opiate detoxification than heroin addicts who did not abuse cocaine. Based on these findings, we insist on the need to develop different treatments for detoxifying patients with this dual addiction.


Biotransformation of nitrogen- and sulfur-containing pollutants during coking wastewater treatment: Correspondence of performance to microbial community functional structure.
Although coking wastewater is generally considered to contain high concentration of nitrogen- and sulfur-containing pollutants, the biotransformation processes of these compounds have not been well understood. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina MiSeq sequencing of the 16S rRNA gene were used to identify microbial functional traits and their role in biotransformation of nitrogen- and sulfur-containing compounds in a bench-scale aerobic coking wastewater treatment system operated for 488 days. Biotransformation of nitrogen and sulfur-containing pollutants deteriorated when pH of the bioreactor was increased to >8.0, and the microbial community functional structure was significantly associated with pH (Mantels test, P < 0.05). The release of ammonia nitrogen and sulfate was correlated with both the taxonomic and functional microbial community structure (P < 0.05). Considering the abundance and correlation with the release of ammonia nitrogen and sulfate, aromatic dioxygenases (e.g. xylXY, nagG), nitrilases (e.g. nhh, nitrilase), dibenzothiophene oxidase (DbtAc), and thiocyanate hydrolase (scnABC) were important functional genes for biotransformation of nitrogen- and sulfur-containing pollutants. Functional characterization of taxa and network analysis suggested that Burkholderiales, Actinomycetales, Rhizobiales, Pseudomonadales, and Hydrogenophiliales (Thiobacillus) were key functional taxa. Variance partitioning analysis showed that pH and influent ammonia nitrogen jointly explained 25.9% and 35.5% of variation in organic pollutant degrading genes and microbial community structure, respectively. This study revealed a linkage between microbial community functional structure and the likely biotransformation of nitrogen- and sulfur-containing pollutants, along with a suitable range of pH (7.0-7.5) for stability of the biological system treating coking wastewater.


Constipation in nocturnal enuresis may interfere desmopressin management success.
Previous studies indicated that the prevalence of constipation in enuretic patients is higher than that in the general population. Several studies have revealed that successful treatment of constipation may be helpful in resolving enuresis. However, constipation affecting the efficacy of desmopressin in treating enuresis remains to be clarified. This study aimed to determine whether the presence of constipation is associated with the efficacy of desmopressin in treating enuresis. Patients diagnosed with nocturnal enuresis (NE) were studied prospectively. Treatment responses in different stratified groups of patients with NE were compared by Chi-squared tests or Wilcoxon rank sum test. A logistic regression model was performed to investigate the relationship between the possible factors and the effectiveness of desmopressin. In children with severe enuresis, patients with constipation had significantly lower complete response rate compared with patients without constipation. The presence of constipation was always related to the effectiveness of desmopressin whether in monosymptomatic NE or non-monosymptomatic patients with NE. With stratification for dose of desmopressin, non-constipated patients who received 0.2 mg of desmopressin had significantly higher complete response rate than patients with constipation. However, in subgroups of mild to moderate NE and 0.4 mg desmopressin, constipation was not associated with treatment response of enuresis. Logistic regression analysis revealed that constipation was significantly related to the effectiveness of desmopressin. This study confirmed the negative effects of constipation in response to desmopressin in patients with NE. To the best of authors knowledge, this work is the first study to evaluate the relationship of constipation in enuretic patients and the efficacy of desmopressin. The presence of constipation negatively affects the response to desmopressin in patients with NE, especially in patients with severe enuresis and in patients prescribed with low dose of desmopressin.


Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo.
Astragalus polysaccharides (APS), which is widely used as a remedy to promote immunity of breast cancer patients, can enhance immune responses and exert anti-tumor effects. In this study, we investigated the effects and mechanisms of APS on macrophage RAW 264.7 and EAC tumor-bearing mice. Griess reaction and ELISA assays revealed that the concentrations of nitric oxide, TNF-α, IL-1β and IL-6 were increased by APS. However, this effect was diminished in the presence of TAK-242 (TLR4 inhibitor) or ST-2825(MyD88 inhibitor). In C57BL/10J (TLR4+/+wild-type) and C57BL/6J (MyD88+/+wild-type) tumor-bearing mice, the tumor apoptosis rate, immune organ indexes and the levels of TNF-α, IL-1β and IL-6 in blood increased and the tumor weight decreased by oral administration of APS for 25 days. APS had no obvious effects on IL-12p70. However, these effects were not significant in C57BL/10ScNJ (TLR4-deficient) and C57BL/B6.129P2(SJL)-Myd88m1.1Defr/J (MyD88-deficient) tumor-bearing mice. qRT-PCR and Western blot indicated that APS stimulated the key nodes in the TLR4-MyD88 dependent signaling pathway, including TLR4, MyD88, TRAF-6, NF-κB and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-κB were not triggered by APS in gene-deficient tumor-bearing mice. Therefore, APS may modulate immunity of host organism through activation of TLR4-mediated MyD88-dependent signaling pathway.


Role of hydrogen sulfide in mercury resistance determined by plasmid of Clostridium cochlearium T-2.
Mercury resistance of Clostridium cochlearium T-2P was found to be controlled by a different mechanism from those reported so far since no mercury-reducing activity was detected in this strain. The H2S generating ability as well as the demethylating activity in this bacterium was eliminated by the treatment of the cured acridine dye and recovered by the conjugation of the cured strain with the parent strain. In addition, the strain which lost their abilities to generate H2S and to decompose methylmercury, showed higher sensitivity to mercurials than the parent strain. From these results, the genes conferring both the activities seemed to reside on the plasmid and the mechanism of mercury resistance was probably based on a detoxification mechanism involving methylmercury decomposition and inactivation of the inorganic mercury with H2S.


Indirect electroreduction as pretreatment to enhance biodegradability of metronidazole.
The removal of metronidazole, a biorecalcitrant antibiotic, by coupling an electrochemical reduction with a biological treatment was examined. Electroreduction was performed in a home-made flow cell at -1.2V/SCE on graphite felt. After only one pass through the cell, analysis of the electrolyzed solution showed a total degradation of metronidazole. The biodegradability estimated from the BOD5/COD ratio increased from 0.07 to 0.2, namely below the value usually considered as the limit of biodegradability (0.4). In order to improve these results, indirect electrolysis of metronidazole was performed with a titanium complex known to reduce selectively nitro compounds into amine. The catalytic activity of the titanium complex towards electroreduction of metronidazole was shown by cyclic voltammetry analyses. Indirect electrolysis led to an improvement of the biodegradability from 0.07 to 0.42. To confirm the interest of indirect electroreduction to improve the electrochemical pretreatment, biological treatment was then carried out on activated sludge after direct and indirect electrolyses; different parameters were followed during the culture such as pH, TOC and metronidazole concentration. Both electrochemical processes led to a more efficient biodegradation of metronidazole compared with the single biological treatment, leading to an overall mineralization yield for the coupling process of 85%.


Dietary preferences in the context of intra-couple dynamics: Relationship types within the German NutriAct family cohort.
To promote healthy diets in older age, a comprehensive understanding of factors influencing dietary behaviour and underlying preferences is essential. Romantic relationships are focal socialisation contexts, in which diet-related preferences and practices are dynamically negotiated. Our aim was to reconstruct intra-couple dynamics shaping dietary preferences and comparatively analyse relationship types among older couples. Data basis was the NutriAct Family Study - a German web-based cohort. Analyses were based on three a priori defined relationship types: 1) both partners' mutual adaptation of dietary preferences (symmetrical convergence), 2) unilateral adaptation (asymmetrical convergence) and 3) persistence of individual preferences. Relationship types were, among others, comparatively analysed using ANOVAs. Intra-couple dynamics within the asymmetrical convergence type were measured by multivariate logistic regression. The dyadic sample consisted of 398 couples resp. N = 796 individuals aged 63.99 years (SD = 6.15). All three relationship types were identified (symmetrical convergence: n = 62, 15.6 %; asymmetrical convergence: n = 199, 50.0 %; persistence: n = 137, 34.4 %). Within the asymmetrical convergence type, women were more likely to take a dominating role compared to their male partners (OR: 24.40; 95%CI: 14.37-41.41). This study demonstrates the fundamental influence of intra-couple dynamics on individual dietary preferences, whereby traditional gender roles have shown to play a central moderating role. Our study findings are relevant for the development and implementation of public health (nutrition) strategies, since they highlight the importance of understanding dietary preferences as jointly constructed and shaped in the intra-couple context, rather than as isolated, individually developed ones. In this context, future research directions and practical implications targeting not only individuals but involving couples are discussed.


Prognostic Significance of Preoperative Lactate Dehydrogenase to Albumin Ratio in Breast Cancer: A Retrospective Study.
We explored the relationship between platelet count to lymphocyte count ratio (PLR), monocyte count to lymphocyte count ratio (MLR), lactate dehydrogenase to albumin ratio (LAR), and long-term survival in patients with breast cancer. We retrospectively analyzed the clinical and follow-up data of 134 patients with breast cancer. The receiver operating characteristic curve (ROC curve) was used to distinguish between the low and high ratio groups. The chi-square test or Fisher's exact test was used to calculate the differences among the investigation factors. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. A P value of <0.05 was considered statistically significant. The median follow-up time was 45 months. The PFS rates in the low group (LAR≤3.4066) at 18 months, 24 months, and 36 months were 100%, 100%, and 97.6%, and those in the high group (LAR > 3.4066) were 97.7%, 94.3%, and 87.3%, respectively. LAR was associated with Age (P=0.002) and BMI (body mass index) (P=0.002). Univariate analysis showed that Tumor size (P=0.027), Node positivity (P<0.001), TNM (tumor-node-metastasis) stage (P<0.001), PLR (P=0.034), MLR (P=0.038), and LAR (P=0.035) were significantly associated with PFS (progression-free survival) in breast cancer patients. Multivariate analysis showed that Node positivity (P<0.001) and LAR (P=0.035) were associated with PFS, while PLR and MLR were not independent prognostic indicators. Preoperative high LAR will be an independent predictor of prognosis in patients with breast cancer.


A simple method for producing a monospecific antiserum against IgM.
To avoid the chemical purification of mastomys IgM, a reliable alternative method for producing a specific anti-mastomys IgM antiserum was developed. It employs the strong cross-reactivity of antisera against mouse serum proteins with mastomys serum proteins. By the immunoelectrophoresis technique, precipitates of mastomys IgM and cross-reacting rabbit anti-mouse IgM were obtained. A rabbit was immunized with these precipitates. Activity against the light chains was removed from the antiserum by passage over an immunoadsorbent column of mastomys IgG. The adsorbed antiserum was found to be specific for determinants on mastomys IgM.


Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting.
The role of hydroxychloroquine (HCQ) in early outpatient management of mild coronavirus disease 2019 (COVID-19) needs further investigation. This study was a multicenter, population-based national retrospective-cohort investigation of 28,759 adults with mild COVID-19 seen at the network of Comprehensive Healthcare Centers (CHC) between March and September 2020 throughout Iran. The baseline characteristics and outcome variables were extracted from the national integrated health system database. A total of 7295 (25.37%) patients who presented with mild COVID-19 within 3-7 days of symptoms onset received HCQ (400 mg twice daily on day 1 followed by 200 mg twice daily for the next four days and were then followed for 14 days). The main outcome measures were hospitalization or death for six months follow-up. COVID-19-related hospitalizations or deaths occurred in 523 (7.17%) and 27 (0.37%) respectively, in HCQ recipients and 2382 (11.10%) and 287 (1.34%) respectively, in non-recipients. The odds of hospitalization or death was reduced by 38% (odds ratio [OR] = 0.62; 95% confidence interval [CI]: 0.56-0.68, p = < 0.001) and 73% (OR = 0.27; 95% CI: 0.18-0.41, p = < 0.001) in HCQ recipients and non-recipients. These effects were maintained after adjusting for age, comorbidities, and diagnostic modality. No serious HCQ-related adverse drug reactions were reported. In our large outpatient national cohort of adults with mild COVID-19 disease who were given HCQ early in the course of the disease, the odds of hospitalization or death was reduced significantly regardless of age or comorbidities.


Tick species infesting humans in the United States.
The data for human tick encounters in the United States (US) presented in this paper were compiled with the goals of: (i) presenting quantitative data across the full range of native or recently established human biting ixodid (hard) and argasid (soft) tick species with regards to their frequency of infesting humans, based on published records of ticks collected while biting humans or crawling on clothing or skin; and (ii) providing a guide to publications on human tick encounters. Summary data are presented in table format, and the detailed data these summaries were based on are included in a set of Supplementary Tables. To date, totals of 36 ixodid species (234,722 specimens) and 13 argasid species (230 specimens) have been recorded in the published literature to infest humans in the US. Nationally, the top five ixodid species recorded from humans were the blacklegged tick, Ixodes scapularis (n=158,008 specimens); the lone star tick, Amblyomma americanum (n=36,004); the American dog tick, Dermacentor variabilis (n=26,624); the western blacklegged tick, Ixodes pacificus (n=4,158); and the Rocky Mountain wood tick, Dermacentor andersoni (n=3,518). Additional species with more than 250 ticks recorded from humans included Ixodes cookei (n=2,494); the Pacific Coast tick, Dermacentor occidentalis (n=809); the brown dog tick, Rhipicephalus sanguineus sensu lato (n=714); the winter tick, Dermacentor albipictus (n=465); and the Gulf Coast tick, Amblyomma maculatum (n=335). The spinose ear tick, Otobius megnini (n=69), and the pajaroello tick, Ornithodoros coriaceus (n=55) were the argasid species most commonly recorded from humans. Additional information presented for each of the 49 tick species include a breakdown of life stages recorded from humans, broad geographical distribution in the US, host preference, and associated human pathogens or medical conditions. The paper also provides a history of publications on human tick encounters in the US, with tables outlining publications containing quantitative data on human tick encounters as well as other notable publications on human-tick interactions. Data limitations are discussed. Researchers and public health professionals in possession of unpublished human tick encounter data are strongly encouraged to publish this information in peer-reviewed scientific journals. In future papers, it would be beneficial if data consistently were broken down by tick species and life stage as well as host species and ticks found biting versus crawling on clothing or skin.


Expression of heme oxygenase-1 protects endothelial cells from irradiation-induced apoptosis.
A common side effect of therapeutic use of ionizing irradiation is endothelial cell damage resulting in a variety of clinical complications. Thus, preservation of endothelial function after irradiation could potentially limit toxicity. Using the murine endothelioma cell line bEnd2 we show here that induction of heme oxygenase-1 (HO-1) by cobalt protoporphyrine IX (CoPP) inhibits irradiation-induced apoptosis. In contrast, HO-1 induction by tin protoporphyrine IX (SnPP), a HO-1 inhibitor, does not affect survival after irradiation. The protective effects of CoPP could be partially reversed by blockade of HO-1 function with SnPP after induction by CoPP. Vice versa, blockade of HO-1 function by SnPP was reversible using CoPP. Treatment with CoPP inhibited cytochrome c release induced by irradiation. These results demonstrate that HO-1 induction and activation prior to irradiation inhibits endothelial apoptosis and might be used for possible cell protection in vivo.


Percutaneous arteriovenous fistula creation with the 4F WavelinQ EndoAVF System.
Percutaneous devices for creation of native arteriovenous fistulae offer an alternative to traditional open surgical techniques. The 4F WavelinQ EndoAVF System was developed as a lower profile alternative to facilitate access through smaller vessels and minimize access site complications; The current report is the original first experience of this device, assessing outcome in 120 patients followed for 6 months. The use of the 4F WavelinQ system in three studies, EASE (32 patients), EASE-2 (24 patients), and the EU postmarket clinical follow-up study (64 patients) was aggregated and analyzed. Patients were followed with duplex ultrasound at discharge and follow-up visits at 1, 3, and 6 months. Primary, assisted primary, and secondary patency rates were evaluated as Kaplan-Meier estimates and standard errors. Time to maturity and time to successful cannulation were defined as the mean ± standard deviation days from the procedure in patients enrolled on dialysis. Procedural success was achieved in 116 patients (96.7%). Primary, assisted-primary, and secondary 6-month patency rates were 71.9% ± 4.5%, 80.7% ± 4.1%, and 87.8% ± 3.3%, respectively. Time to maturity averaged 41 ± 17 days. Time to successful cannulation averaged 68 ± 51 days. Device-related serious adverse events were reported in 3 of 120 patients (2.5%) and procedure-related serious adverse events occurred in 7 of 120 patients (5.8%). Arterial or venous access complications were not reported in any of the patients. Access circuit reinterventions were performed in 23 patients (19.2%), split between those performed for EndoAVF maturation (13/120 [10.8%]) and maintenance (11/120 [9.2%]). Percutaneous creation of native dialysis fistulae with the 4F WavelinQ EndoAVF System is safe and effective, with favorable durability and a low rate of serious complications and reinterventions through 6-month follow-up. Use of the 4F device allows for percutaneous fistula creation between the radial artery and radial vein or the ulnar artery and ulnar vein. These findings suggest that the 4F device is a useful percutaneous alternative to open surgical AVF or endovascular AVF with larger bore devices.


Detection of surface antigen expression of pre- and post-cultured normal adult's bone marrow cells by using ABC technique and its significance.
The expression of surface antigens on both normal adult's bone marrow and multipotential progenitor cells (CFU-Mix) was detected by use of ABC technique. The culture system of CFU-Mix was an ideal model for studying the differentiation direction of hematopoietic cells. The monoclonal antibodies (McAb) CD3, CD4, CD8 specific for T-lymphocytic lineage, CD22 for B-lymphocytic lineage and CD11, CD13, CD14 for granulocytomonocytic lineage were all demonstrated in certain proportion in cultured CFU-Mix, which might be associated with the control of hematopoiesis. A decrease in the positive rate of OKT9 and CD34 in cultured cells might be related to the differentiation of hematopoietic cells. SZ-2 and SZ-21 could contribute to the identification of the presence of megakaryocytes in CFU-Mix.


Validation of brief screening instruments for internalizing and externalizing disorders in Mozambican adolescents.
Mental disorders are the leading cause of disability for youth worldwide. However, there is a dearth of validated, brief instruments to assess mental health in low- and middle-income countries (LMIC). We aimed to facilitate identification of mental disorders in LMIC contexts by adapting and validating measures of internalizing and externalizing disorders for adolescents in Mozambique, an LMIC in southeastern Africa. We selected instruments with good support for validity in high-income and other LMIC settings: the Patient Health Questionnaire Adolescent (PHQ-A), Generalized Anxiety Disorders 7 (GAD-7), and Strengths and Difficulties Questionnaire (SDQ). Instruments were adapted by local and international mental health specialists followed by cognitive interviews (n = 48) with Mozambican adolescents. We administered the instruments along with the Miniature International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)to 485 adolescents aged 12-19 years attending two secondary schools in Maputo City, Mozambique. One week later, we re-administered instruments to a randomly selected sample of 49 adolescents. Participants were 66.2% (n = 321) female and the average age was 15.9 (S.D = 1.7).Internal consistency (alpha = 0.80, PHQ-A; 0.84, GAD-7; 0.80, SDQ) and test-retest reliabilty (ICC = 0.74, PHQ-A; 0.70, GAD-7; 0.77, SDQ) were acceptabe for the PHQ-A, GAD-7, and the full SDQ. The SDQ internalizing subscale showed poor test-retest reliability (ICC = 0.63) and the SDQ externalizing subscale showed poor internal consistency (alpha = 0.65). All instruments demonstrated good sensitivity and specificity (> 0.70). Youden's index identified optimal cutoff scores of 8 for the PHQ-A, 5 for the GAD-7, 10 for the SDQ internalizing and 9 for the SDQ externalizing subscales, though a range of scores provided acceptable sensitivity and specificity. Our data supports reliability and validity of the PHQ-A, GAD-7, and SDQ instruments for rapidly assessing mental health problems in Mozambican adolescents. Use of these tools in other contexts with limited specialists may asist with expanding mental health assessment. Specific instrument and cutoff selection should be based on screening goals, treatment resources, and program objectives.


Gum health - who cares?
Much of the British population have poor gum health which can affect their daily lives and general health. Surprisingly, we don't often hear from the public whether they care about this situation. Is this a lack of interest or a lack of opportunity to be heard? In addition, gum health, like overall health, requires people to take care of themselves and to take ownership of their condition. Whose responsibility is it to promote this care? In this article, a BSP Patient Forum member (Barbara Sturgeon) and clinician (Professor Ian Needleman) explore and discuss the issues surrounding: gum health - who cares?


The Nordic diet is characterized by a high content of plant-based food and a limited content of animal and processed food. Intervention studies show with moderate evidence that Nordic diet reduces risk factors for cardiovascular diseases (blood pressure, total and low-density lipoprotein cholesterol). Observational studies show with weak evidence that Nordic diet reduces the risk of cardiovascular diseases e.g. stroke and myocardial infarcts and with moderate evidence reduces cardiovascular death. Thus, Nordic diet appears beneficial for cardiovascular health as well as for the climate and the environment, as argued in this review.


Incorporation of Cró thermal water in a dermocosmetic formulation: cytotoxicity effects, characterization and stability studies and efficacy evaluation.
Development of cosmetic formulations to provide a controlled release of hydrophilic active compounds from mineral medicinal waters constitutes an attractive challenge. The objective of this study was the development and the characterization of a dermocosmetic gel formulation with Cró thermal water, from Beira Interior of Portugal, as a major functional ingredient. Concentrations of mineral chemical elements of Cró thermal water were previously determined by inductively coupled plasma-optical emission spectrometry or mass spectrometry and cytotoxicity assays using thermal water were carried out on normal human dermal fibroblasts (NHDF) cells. Then, the Cró thermal water was included (more than 90%) in a developed gel formulation that was characterized through rheological and texture analysis and submitted to stability assays during 30 days. The effects on the skin volunteers, namely skin pH, the degree of hydration, transepidermal water loss and skin relief, were evaluated through non-invasive biometric techniques. A gel formulation including purified water was used as a control. Cró thermal water is rich on several chemical elements in particular sodium, silica, potassium and calcium besides some trace elements, with important functions for the skin. NHDF cells adhered and proliferated in the presence of thermal water confirming the biocompatibility of the major component of the gel formulation. The developed gel formulation based on thermal water resulted in an improvement of textural parameters, comparing with the purified water-based one. Significant improvements in the cutaneous biometric parameters (degree of hydration, transepidermal water loss and skin relief) of volunteers were also registered for the gel formulation containing thermal water. This study demonstrated for the first time the potential benefits of Cró thermal water in a gel formulation to be used in cosmetic and dermatological applications.


Epidemiologic characteristics of traumatic fractures in elderly patients during the outbreak of coronavirus disease 2019 in China.
This study aimed to describe the epidemiologic characteristics of fracture in the elderly during the COVID-19. This was a retrospective multi-centre study, which included patients who sustained fractures between 20 January and 19 February 2020. The collected data included patients' demographics (age and gender), injury-related (injury type, fracture location, injury mechanism, places where fracture occurred), and treatment modality. SPSS 23.0 was used to describe the data and perform some analysis. A total of 436 patients with 453 fractures were included; there were 153 males and 283 females, with an average age of 76.2 years (standard deviation, SD, 7.7 years; 65 to 105). For either males or females, 70-74 years was the most commonly involved age group. A total of 317 (72.7%) patients had their fractures occurring at home. Among 453 fractures, there were 264 (58.3%) hip fractures, accounting for 58.3%. Fall from standing height was the most common cause of fracture, making a proportion of 89.4% (405/453). Most fractures (95.8%, 434/453) were treated surgically, and 4.2% (19/453) were treated by plaster fixation or traction. Open reduction and internal fixation (ORIF) was the most used surgical method, taking a proportion of 49.2% (223/453). These findings highlighted the importance of primary prevention (home prevention) measures and could be used for references for individuals, health care providers, or health administrative department during the global pandemic of COVID-19.


The Effect of Shoulder Injury Prevention Program on Shoulder Isokinetic Strength in Young Male Volleyball Players.
The purpose of this study was to examine the effects of an eight-week 11 + S programme on isokinetic shoulder strength in young male volleyball players. Twenty-eight top-level young male volleyball players were recruited for this study. The players were randomly assigned into intervention (14 players) and control (14 players) groups. The intervention group performed the 11 + S as a warm-up before training at least three times a week for eight weeks. Dominant shoulder strength was measured using an isokinetic dynamometer at 60°/s and 180°/s. The functional deceleration ratio (FDR) was calculated as a functional strength profile. 20% FDR improvement after eight weeks of 11 + S at 180°/s (p = 0.003) were observed. No other statistically significant effects for shoulder strength improvement was observed (p > 0.05). Eight weeks of 11 + S warm-up programme improved the glenohumeral muscle imbalance by increasing the functional deceleration ratio (FDR) of shoulder muscles in young male volleyball players.


UV-Resistant Self-Healing Emulsion Glass as a New Liquid-like Solid Material for 3D Printing.
Directly writing 3D structures into supporting mediums is a relatively new developing technology in additive manufacturing. In this work, durable and recyclable liquid-like solid (LLS) materials are developed as supporting mediums that are stable for both UV and thermal solidification. Our LLS material is comprised of densely packed oil droplets in a continuous aqueous medium, known as emulsion glass. Its elastic nature emerges from the jammed structure of oil droplets, which offers this LLS material rapidly self-healing ability. Moreover, the yield stress of the glass is relatively low and can be tuned by the viscosity and weight percentage of oil. The capability of the emulsion glass as supporting mediums is successfully demonstrated by directly writing and then curing designed structures. The emulsion glass has been repeatedly used at least 6 times upon exposure to UV irradiation and heat, implying it can expand the applications of supporting medium to the writing process involving UV- and thermal-curable inks simultaneously.


Dynamic Flux Analysis: An Experimental Approach of Fluxomics.
Metabolic flux analysis represents an essential perspective to understand cellular physiology and offers quantitative information to guide pathway engineering. A valuable approach for experimental elucidation of metabolic flux is dynamic flux analysis, which estimates the relative or absolute flow rates through a series of metabolic intermediates in a given pathway. It is based on kinetic isotope labeling experiments, liquid chromatography-mass spectrometry (LC-MS), and computational analysis that relate kinetic isotope trajectories of metabolites to pathway activity. Herein, we illustrate the mathematic principles underlying the dynamic flux analysis and mainly focus on describing the experimental procedures for data generation. This protocol is exemplified using cyanobacterial metabolism as an example, for which reliable labeling data for central carbon metabolites can be acquired quantitatively. This protocol is applicable to other microbial systems as well and can be readily adapted to address different metabolic processes.


Skin carotenoids: a biomarker of fruit and vegetable intake in children.
Studies of adult subjects have found a strong correlation between serum carotenoids and skin carotenoids measured by resonance Raman spectroscopy (RRS). No published studies have examined correlations between skin and serum carotenoids among children. We aimed to validate skin RRS methodology against serum carotenoid measurements by high-performance liquid chromatography and to determine whether RRS can be used as a valid biomarker of fruit and vegetable (F/V) intake among children. In our cross-sectional study, participants were 45 healthy children aged 5 to 17 years who provided three blood samples used to assess serum carotenoid concentrations and three RRS skin measurements of the palm within a 4-week period. Dietary intake of F/V was assessed three times within 4 weeks using a 27-item food frequency questionnaire (FFQ) and an automated multiple-pass 24-hour daily recall. Estimates of intake from three FFQs, completed at least 7 days apart, were averaged. Estimates of intake from 24-hour daily recalls were collected on 2 weekdays and 1 weekend day and averaged. Levels of skin and serum carotenoids were highly correlated (R(2)=0.62; P<0.001). A linear regression model, controlling for child's weight and scanner unit, predicted that for every unit increase of total F/V from FFQ and total F/V as assessed by 24-hour daily recall, RRS intensity was predicted to increase by 3,798 (P=0.001) and 3,504 (P=0.001), respectively. Similar results were observed for reported high-carotenoid vegetable intake. Total carotenoid and beta carotene levels from 24-hour daily recalls correlated to total serum carotenoids levels (P<0.01 and P<0.05, respectively). Total carotenoid, alpha carotene, and beta carotene levels from the 24-hour daily recalls correlated to RRS (P<0.01). Skin carotenoids measured by RRS were strongly correlated with serum carotenoid levels and were positively associated with estimates of intake from FFQ and an automated multiple-pass 24-hour daily recall among children aged 5 to 17 years. Skin carotenoids may be used as valid biomarker of F/V intake among children.


Protection against cis-dichlorodiammine Pt (II) cytotoxicity in vitro by cysteamine.
EMT6/SF cells exposed to cis-dichlorodiammine Pt(II) (DDP) for 1 hr in the presence of 10 mM cysteamine (MEA) survived better than cells treated with DDP alone (DMF-3.1). MEA added to cultures after removal of DDP also protected, even when the two exposures were separated by as long as 4 hr. Protection by MEA was concentration dependent: no significant protection was observed below 1 mM and maximum protection required 5 mM. When cells were incubated with 10 mM MEA immediately after removal of DDP, survival increased as a function of the length of exposure to MEA, reaching a maximum at 2 hr.


Breast MRI BI-RADS 3: Impact of Patient-Level Factors on Compliance With Short-Term Follow-Up.
A BI-RADS 3 assessment on breast MRI is given when a finding is estimated to have less than 2% chance of breast cancer. Patients in this category are typically recommended to return for a 6-month follow-up MRI. Compliance with this recommendation is low, and we aim to understand which factors are associated with compliance. All patients with an MRI examination given a BI-RADS category 3 between February 1, 2011, and June 30, 2016, were retrospectively reviewed. Patient demographics and breast-related medical history were extracted from the electronic medical record. Patients presenting for follow-up MRI between 3 and 10 months were considered compliant. Univariate and multivariate analysis was performed to identify which patient-level factors were associated with compliance with follow-up MRI. Overall, 190 women with a BI-RADS 3 assessment on MRI were included in the study. Of these women, 106 were compliant with the recommended follow-up MRI (57.3%), 34 had delayed follow-up (18.4%), and 45 were noncompliant (24.3%). Reason for examination, personal history of breast cancer, and family history of breast cancer were significantly associated with compliance. We found that 75.7% of patients had a follow-up MRI after a BI-RADS 3 assessment, but only 57.3% were timely in their follow-up. Our data suggest that there may be subsets of patients who would benefit from additional support and resources to help increase overall compliance and timely compliance.


DANA elements: a family of composite, tRNA-derived short interspersed DNA elements associated with mutational activities in zebrafish (Danio rerio).
DNA is the first SINE isolated from zebrafish (Danio rerio) exhibiting all the hallmarks of these tRNA-derived elements. DANA is unique in its clearly defined substructure of distinct cassettes. In contrast to generic SINE elements, DANA appears to have been assembled by insertions of short sequences into a progenitor, tRNA-derived element. Once associated with each other, these subunits were amplified as a new transposable element with such a remarkable success that DANA-related sequences comprise approximately 10% of the modern zebrafish genome. At least some of the sequences comprised by the full-length element were capable of movement, forming a new group of mobile, composite transposons, one of which caused an insertional mutation in the zebrafish no tail gene. Being present only in the genus Danio, and estimated to be as old as the genus itself, DANA may have played a role in Danio speciation by massive amplification and genome-wide dispersion. There are extensive DNA polymorphisms between zebrafish populations and strains detected by PCR amplification using primers specific to DANA, suggesting that the DANA element will be useful as a molecular tool for genetic and phylogenetic analyses.


Orofacial granulomatosis associated with hypersensitivity to dental amalgam.
Orofacial granulomatosis is a clinicopathologic entity characterized by chronic swelling of the lip and possible soft tissues in the orofacial region owing to granulomatous inflammation of unknown cause. We present 3 cases of orofacial granulomatosis associated with allergic contact dermatitis to dental materials. Previous treatment with corticosteroids did not have any therapeutic effect. Patch testing revealed a positive reaction to several allergens, including dental amalgam and mercury in 2 cases. A lymphocyte transformation test modified for metals was used to evaluate lymphocyte reactivity. After the removal of the suspected allergens, all patients experienced recovery within 1 month, with the exception of the lip swelling, which gradually subsided over several months.


A new biocompatible and antibacterial phosphate free glass-ceramic for medical applications.
In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility.


Surgical management of "pus-pot" perineum.
Ten cases of disabling "pus-pot" perineum secondary to hidradenitis suppurativa, urethral stricture disease, condyloma acuminatum and anoperineal fistula were treated by wide excision of involved tissues. In 7 men the testicles were transposed to thigh pouches, and in 3 the entire penile skin was excised and replaced with a skin graft.


"A special defence": a psychiatric approach to formalizing euthanasia.
Domestic and world opinion is gradually changing towards the idea of tolerating or even legalizing active euthanasia. The implications of this are examined using Foulke's concept of the 'levels' in group discussions. Psychiatrists have a unique experience in using the statutory mental health legislation, in addition to the ordinary law, to regulate medical care. A new 'special defence' is suggested, to be enacted by Parliament, intended to justify, but also designed to control, deliberate acts of medical euthanasia.


Asaronic acid inhibits ER stress sensors and boosts functionality of ubiquitin-proteasomal degradation in 7β-hydroxycholesterol-loaded macrophages.
Misfolded proteins are formed in the endoplasmic reticulum (ER) due to diverse stimuli including oxidant production, calcium disturbance, and inflammatory factors. Accumulation of these non-native proteins in the ER evokes cellular stress involving the activation of unfolded protein response (UPR) and the execution of ER-associated degradation (ERAD). Naturally-occurring plant compounds are known to interfere with UPR due to their antioxidant and anti-inflammatory activities, leading to inhibition of ER stress. However, there are few studies dealing with the protective effects of natural compounds on the functionality of ERAD. The current study examined whether asaronic acid enhanced ubiquitin-proteasomal degradation in J774A.1 murine macrophages exposed to 7β-hydroxycholesterol, a risk factor for atherosclerosis. Asaronic acid (2,4,5-trimethoxybenzoic acid), identified as one of purple perilla constituents, has anti-diabetic and anti-inflammatory effects. Little is known regarding the effects of asaronic acid on the ERAD process and the ubiquitin-proteasomal degradation. Murine macrophages were incubated with 28 μM 7β-hydroxycholesterol in absence and presence of 1-20 μΜ asaronic acid for up to 24 h. Nontoxic asaronic acid in macrophage diminished the activation of the ER stress sensors of ATF6, IRE1 and PERK stimulated by 7β-hydroxycholesterol. This methoxybenzoic acid down-regulated the oxysterol-induced expression of EDEM1, OS9, Sel1L-Hrd1 and p97/VCP1, all required for the recognition, recruitment and dislocation of misfolded proteins. On the other hand, asaronic acid enhanced the ubiquitin-proteasomal degradation of non-native proteins dislocated to the cytosol by 7β-hydroxycholesterol, which entailed the induction of the chaperones of Hsp70 and CHIP and the increased colocalization of ubiquitin and proteasomes. Taken together, asaronic acid attenuated the induction of the UPR-associated sensors and the dislocation-linked transmembrane components in the ER. Conversely, this compound enhanced the proteasomal degradation of dislocated non-native proteins in concert with the chaperones of Hsp70 and CHIP through ubiquitination. These observations demonstrate that asaronic acid may be a potent atheroprotective agent as a natural chaperone targeting ER stress-associated macrophage injury.


predCar-site: Carbonylation sites prediction in proteins using support vector machine with resolving data imbalanced issue.
The carbonylation is found as an irreversible post-translational modification and considered a biomarker of oxidative stress. It plays major role not only in orchestrating various biological processes but also associated with some diseases such as Alzheimer's disease, diabetes, and Parkinson's disease. However, since the experimental technologies are costly and time-consuming to detect the carbonylation sites in proteins, an accurate computational method for predicting carbonylation sites is an urgent issue which can be useful for drug development. In this study, a novel computational tool termed predCar-Site has been developed to predict protein carbonylation sites by (1) incorporating the sequence-coupled information into the general pseudo amino acid composition, (2) balancing the effect of skewed training dataset by Different Error Costs method, and (3) constructing a predictor using support vector machine as classifier. This predCar-Site predictor achieves an average AUC (area under curve) score of 0.9959, 0.9999, 1, and 0.9997 in predicting the carbonylation sites of K, P, R, and T, respectively. All of the experimental results along with AUC are found from the average of 5 complete runs of the 10-fold cross-validation and those results indicate significantly better performance than existing predictors. A user-friendly web server of predCar-Site is available at http://research.ru.ac.bd/predCar-Site/.


Radiographic and MRI Assessment of the Thrower's Elbow.
Throwing athletes are vulnerable to elbow injuries, especially in the medial elbow, related to high stress and valgus load in both acute and chronic settings as a result of this complex biomechanical action. This current review details the relevant anatomy and imaging features of common elbow pathology identified with radiographs and MRI in throwing athletes. Although elbow pathology in throwing athletes is well documented, advances in imaging technology and technique, particularly with MRI, have allowed for more detailed and accurate imaging description and diagnosis. Pathology of thrower's elbow occurs in predictable patterns and can be reliably identified radiologically. Clinical history and physical examination should guide radiologic evaluation initially with radiographs and followed by an MRI optimized to the clinical question. Constellation of clinical, physical, and radiologic assessments should be used to guide management.