Influence of enamel conditioning on the shear bond strength of different adhesives.
Phosphoric acid etching is the gold standard for enamel conditioning. However, it is possible that air abrasion or a combination of air abrasion and etching might result in enhanced adhesion. The aim of this study was to investigate the effect of different enamel conditioning methods on the bond strength of six adhesives. Three different enamel conditioning procedures (phosphoric acid etching, air abrasion, air abrasion + phosphoric acid etching) were evaluated for their influence on the shear bond strength of six different adhesives (Transbond™ XT, Cool-Bond™, Fuji Ortho LC, Ultra Band-Lok, Tetric(®) Flow, Light-Bond™). Each group consisted of 15 specimens. Shear forces were measured with a universal testing machine. The scores of the Adhesive Remnant Index (ARI) were also analyzed. There were no significant differences between phosphoric acid etching and air abrasion + phosphoric acid etching. Air abrasion as a single conditioning technique led to significantly lower shear forces. The ARI scores did not correlate with the shear strengths measured. There were greater variations in shear forces for the different adhesives than for the conditioning techniques. The highest shear forces were found for the conventional composites Transbond™ XT and Cool- Bond™ in combination with conventional etching. Air abrasion alone and in combination with phosphoric acid etching showed no advantages compared with phosphoric acid etching alone and, therefore, cannot be recommended.


Expression and phosphorylation of the na-pump regulatory subunit phospholemman in heart failure.
Intracellular [Na] is approximately 3 mmol/L higher in heart failure (HF; in our arrhythmogenic rabbit model), and this can profoundly affect cardiac Ca and contractile function via Na/Ca exchange and Na/H exchange. Na/K-ATPase is the primary mechanism of Na extrusion. We examine here in HF rabbits (and human hearts) expression of Na/K-ATPase isoforms and phospholemman (PLM), a putative Na/K-ATPase regulatory subunit that inhibits pump function and is a major cardiac phosphorylation target. Na/K-ATPase alpha1- and alpha2-isoforms were reduced in HF in rabbit ventricular homogenates (by 24%) and isolated myocytes (by 30% and 17%), whereas alpha3 was increased (50%) in homogenates and decreased (52%) in myocytes (P<0.05). Homogenate Na/K-ATPase activity in left ventricle was also decreased in HF. However, we showed previously that Na/K-ATPase characteristics in intact ventricular myocytes were unaltered in HF. To reconcile these findings, we assessed PLM expression, phosphorylation, and association with Na/K-ATPase. PLM coimmunoprecipitated with Na/K-ATPase alpha1 and alpha2 in control and HF rabbit myocytes. PLM expression was reduced in HF by 42% in isolated rabbit left ventricular (LV) myocytes, by 48% in rabbit LV homogenates, and by 24% in human LV homogenate. The fraction of PLM phosphorylated at Ser-68 was increased dramatically in HF. Our results are consistent with a role for PLM analogous to that of phospholamban for SR Ca-ATPase (SERCA): inhibition of Na/K-ATPase function that is relieved on PLM phosphorylation. So reduced Na/K-ATPase expression in HF may be functionally offset by lower inhibition by PLM (because of reduced PLM expression and higher PLM phosphorylation).


Birthweight, parental age, birth order and breast cancer risk in African-American and white women: a population-based case-control study.
Much recent work has focused on hypotheses that very early life exposures influence adult cancer risk. For breast cancer it has been hypothesized that high in utero estrogen exposure may increase risk. We used data from the Carolina Breast Cancer Study, a population-based case-control study of incident breast cancer in North Carolina, to examine associations for three possible surrogates of high prenatal estrogen exposure: weight at birth, maternal age, and birth order. We also examined paternal age. Birthweight analyses were conducted for white and African-American women born in North Carolina on or after 1949 (196 cases, 167 controls). Maternal age was analyzed for US born participants younger than 49 years of age (280 cases, 236 controls). There was a weak inverse association between birthweight in the highest tertile and breast cancer overall (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.4-1.2), although associations differed by race (OR 0.5, 95% CI 0.2-1.0, and OR 1.0, 95% CI 0.5-2.1 for African-American and white women, respectively). For maternal age there was an approximately threefold increase in risk in women whose mothers were older than 22 years of age, relative to 19-22 years of age, when the women were born. After adjustment for maternal age, older paternal age increased risk in the oldest and youngest age categories (relative to 23-27 years of age at the woman's birth: OR 1.6, 95% CI 0.8-3.1 for age 15-22 years; OR 1.2, 95% CI 0.7-2.2 for age 28-34 years; and OR 1.5, 95% CI 0.7-3.2 for age 35-56 years). There was no association with older paternal age for white women alone. After adjustment for maternal age (265 cases, 224 controls), a birth order of fifth or higher relative to first had an inverse association with breast cancer for women younger than 49 years old (OR 0.6, 95% CI 0.3-1.3). Although the CIs are wide, these results lend support to the possibility that the prenatal period is important for subsequent breast cancer risk, but they do not support the estrogen hypothesis as a unifying theory for the influence of this period.


Understanding the impact of the COVID-19 pandemic on stress, mood, and substance use among young adults in the greater Minneapolis-St. Paul area: Findings from project EAT.
There is a need to understand how the ongoing COVID-19 pandemic has affected the mental and behavioral health of young adults in the U.S. This study used quantitative and qualitative survey data to identify young adults at highest risk for psychological distress during the U.S. outbreak of COVID-19 and to further understand how the pandemic has impacted their stress, mood, and substance use. Participants were 670 young adult cohort members (ages 21-29) of the population-based longitudinal study EAT 2010-2018 who participated in the C-EAT study (COVID-19 Eating and Activity over Time). Among the sample, 84% (n = 561) reported pandemic-related changes to their mood or stress and 33% (n = 221) reported changes to their substance use. Linear regression analyses identified several meaningful risk factors for higher psychological distress during the pandemic, including female gender, White race, higher pre-pandemic depressive symptoms and perceived stress, and lower pre-pandemic stress management ability. A thematic analysis further identified five major themes related to changes in stress and mood following the COVID-19 outbreak describing specific emotional reactions, stress related to the direct impact of the pandemic as well as interpersonal connectedness and economic factors, and strategies for managing stress. In addition, two major themes were identified related to substance use during the pandemic detailing specific changes in and motivations for substance use. These findings underscore the need to develop effective, scalable, and rapidly deployable public health resources that target the stressors commonly experienced among young adults to improve their psychological wellbeing during this pandemic.


Overexpression of Glutathione S-Transferase Genes in Field λ-Cyhalothrin-Resistant Population of Cydia pomonella: Reference Gene Selection and Expression Analysis.
Analysis of the glutathione S-transferase (GST) gene expression in an insecticide-resistant strain of Cydia pomonella using real-time quantitative polymerase chain reaction is a key step toward more mechanism studies that require suitable reference genes with stable expression. Here, nine commonly used reference genes were selected, and their expression stabilities were analyzed. Results showed that EF-1α was the most stable reference gene in all of the experimental sets. The combinations of EF-1α and 18S, EF-1α and RPL12, and EF-1α and GAPDH were sufficient for normalization of gene expression analysis accurately in developmental stages, tissues, and larvae exposed to sublethal dose of λ-cyhalothrin, respectively. Additionally, the suitability of particular reference genes was verified by analyzing the spatiotemporal and insecticide-induced expression profiles of CpGSTe3, CpGSTd3, and CpGSTd4, which were overexpressed in a λ-cyhalothrin-resistant population from northeast China. These genes were used to confer the practicability of reference genes chosen in this study.


Immunogold electron-microscopic localisation of calpain I in skeletal muscle of rats.
By using a double-affinity-purified first antibody and colloidal gold-conjugated second antibody, it is shown that calpain I (a cysteine proteinase activated by micromolar concentrations of Ca2+) has a predominant intracellular location in the I-band region of the extensor digitorum longus (EDL) muscle of the rat, but is not exclusively associated with the Z-line.


Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.
In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF. We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62). In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.


Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.
Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 μs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. MicroTransponder.


Bariatric Surgery in Youth: the Perspective of Dutch Pediatricians, Parents, and Adolescents.
Recent studies have indicated that bariatric surgery is effective for the treatment of youth with severe obesity. The attitudes of pediatricians, parents, and adolescents regarding this topic remain unclear. Therefore, the aim of this study was to assess the current thoughts and beliefs of Dutch pediatricians, parents, and adolescents regarding bariatric surgery in youth. An online survey containing twenty questions on bariatric surgery in youth was distributed to pediatricians of the Dutch Society of Pediatrics. Parents and adolescents who participated in an interdisciplinary care program for overweight, obesity, and severe obesity filled out an online survey of twelve questions. One hundred and twenty-one pediatricians, 49 parents, and 19 adolescents completed the surveys. Seventy-two pediatricians (59.5%) considered bariatric surgery to be an effective treatment for youth with severe obesity when conventional treatment fails, and intend to refer patients for bariatric surgery. The most frequently suggested conditions for bariatric surgery were a minimum age of 16 years (n = 59, 48.7%), a BMI threshold of 40 kg/m2 (n = 51, 42.2%), and a minimum Tanner stage of IV (n = 59, 48.8%). Thirty parents (61.2%) and fourteen adolescents (73.7%) responded that bariatric surgery should become available for youth with severe obesity. Dutch pediatricians, parents, and adolescents increasingly accept bariatric surgery as a treatment modality in youth with severe obesity who do not respond successfully to lifestyle intervention. Whether pediatricians will actually refer youth for bariatric surgery remains to be seen when this treatment option will be implemented in the Netherlands.


Understanding B-cell tolerance through the use of immunoglobulin transgenic models.
The appearance of autoantibodies in autoimmune diseases such as lupus suggests that B-cell tolerance to self is breached. Hence it becomes important to unravel the precise cellular and molecular mechanisms that are responsible for violations in various B-cell tolerance checkpoints in autoimmune diseases. B-cell immunoglobulin or B-cell receptor transgenic models have been of immense aid in uncovering many of these key tolerance checkpoints during normal B-cell development. By breeding these transgenic models onto mice that are engineered to lack or hyperexpress various B-cell molecules, including signaling intermediates, researchers have delineated the role of these molecules in B-cell tolerance. These transgenic models have also been useful in delineating the impact of various lupus prone genomes and lupus susceptibility loci on B-cell tolerance. This review focuses on some of the more well-studied B-cell receptor transgenic models and the lessons they have taught us over the past two decades.


Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF.
Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline. Iron deficiency was defined as a ferritin level <100 ng/mL or a transferrin saturation <20% and a ferritin level 100 to 299 ng/mL. Additional biomarkers of iron metabolism, including soluble transferrin receptor, erythropoietin, and hepcidin were measured at baseline and 12 months after randomization. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized in DAPA-HF, 3009 had ferritin and transferrin saturation measurements available at baseline, and 1314 of these participants (43.7%) were iron deficient. The rate of the primary outcome was higher in patients with iron deficiency (16.6 per 100 person-years) compared with those without (10.4 per 100 person-years; P<0.0001). The effect of dapagliflozin on the primary outcome was consistent in iron-deficient compared with iron-replete patients (hazard ratio, 0.74 [95% CI, 0.58-0.92] versus 0.81 [95% CI, 0.63-1.03]; P-interaction=0.59). Similar findings were observed for cardiovascular death, heart failure hospitalization, and all-cause mortality. Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo. Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline. URL: https://www. gov; Unique identifier: NCT03036124.


Cytokine toxicity in insulin-producing cells is mediated by nitro-oxidative stress-induced hydroxyl radical formation in mitochondria.
Although nitric oxide (NO) and oxidative stress both contribute to proinflammatory cytokine toxicity in pancreatic β-cells during type 1 diabetes mellitus (T1DM) development, the interactions between NO and reactive oxygen species (ROS) in cytokine-mediated β-cell death have not been clarified. Exposure of insulin-producing RINm5F cells to IL-1β generated NO, while exposure to a combination of IL-1β, TNF-α, and IFN-γ, which simulates T1DM conditions, generated both NO and ROS. In theory, two reactions between NO and ROS are possible, one with the superoxide radical yielding peroxynitrite, and the other with hydrogen peroxide (H(2)O(2)) yielding hydroxyl radicals. Results of the present work exclude peroxynitrite involvement in cytokine toxicity to β-cells because its generation did not correlate with the toxic action of cytokines. On the other hand, we show that H(2)O(2), produced upon exposure of insulin-producing cell clones and primary rat islet cells to cytokines almost exclusively in the mitochondria, reacted in the presence of trace metal (Fe(++)) with NO forming highly toxic hydroxyl radicals, thus explaining the severe toxicity that causes apoptotic β-cell death. Expression of the H(2)O(2)-inactivating enzyme catalase in mitochondria protected against cytokine toxicity by preventing hydroxyl radical formation. We therefore conclude that proinflammatory cytokine-mediated β-cell death is due to nitro-oxidative stress-mediated hydroxyl radical formation in the mitochondria.


Interaction between Sendai virus and KB cell lines with altered cell fusion ability: a study employing electron spin resonance.
The nature of the interaction between Sendai virus and Sil mutant cells was examined by measuring a change in ESR spectrum of spin-labeled phosphatidylcholine molecules on the viral envelope. When spin-labeled virus was incubated with the Sil cells that had a reduced ability to respond to virus-induced cell fusion, interchange of the phospholipid molecules between viral envelope and cell surface membrane occurred to a smaller extent than that observed with parental cells. Moreover, the degree of the interchanging correlated with the degree of the fusion capacity of the mutant lines. The results show that the mutant cells carry such a lesion(s) on their surface membranes that the viral envelopes can hardly fuse into them.


Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy.
Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori. We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.


Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.
Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV+ MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including HES6, SOX2, ATOH1, and KRT20 Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV+ MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor.


Food and heart-the nutritional jungle: Patients' experiences of dietary habits and nutritional counselling after coronary artery bypass grafting.
The aim of the study was to examine patients' experience of dietary habits and nutritional counselling in the early period during hospitalisation after coronary artery bypass surgery (CABG). Undergoing CABG, patients have two different nutritional needs, extra proteins and calories for the first period after surgery and a heart-healthy diet when the recovery period is over. These needs can be difficult to manage for the patients. Qualitative study. Interviews were conducted and analysed within a phenomenological-hermeneutic frame inspired by the French philosopher Paul Ricoeur. Patients undergoing CABG were interviewed 4-5 days after surgery at Odense University Hospital from March to May, 2017. The study adhered to the COREQ guidelines. In total, 15 patients were interviewed (mean age 65 years, 87% men). After analysing the interviews following themes emerged, "Different needs-the nutritional jungle", "Food and heart-the lacking attention," and "The force of habits-being under the influence from spouses on dietary habits". The interviewed patients had no or only a little knowledge about how to eat after heart surgery. In general, they experienced a lack of attention to nutritional counselling by the nursing staff during hospitalisation. Furthermore, the health behaviour of men seems to be different from women's, and therefore, interventions aiming at optimising men's health might be prioritised. Finally, spouses have a great influence on eating habits, why they should be involved in nutritional counselling. This study provides important and relevant knowledge about patients' lacking knowledge about nutrition. When planning nutritional measures, whether it is promoting healing after heart surgery or preventing progression of arteriosclerosis, the study contributes with suggestions as to which factors should be considered in this process-men's health behaviour and spouses' influence on dietary habits in the household.


Occurrence of radon in groundwater of Saudi Arabia.
Samples were collected from 1025 wells supplying drinking water to the 13 regions of Saudi Arabia and analyzed for radon concentrations. The weighted radon median value for the entire country was found to be 4.62 Bq L(-1) with a range of 0.01-67.4 Bq L(-1). The percentage of samples with radon concentration equal to or greater than 11.1 Bq L(-1) (US EPA proposed MCL) was found to be 19.22%. The range of radon in shallow wells varied between 0.06 and 67.4 Bq L(-1) (median value 5.1 Bq L(-1)) and between 0.06 and 40.9 Bq L(-1) (median value 5.34 Bq L(-1)) for deep wells. However, 50% of the samples had radon concentrations equal to or greater than 4.0 and 2.87 Bq L(-1) for the shallow and deep wells, respectively. Correlation of well depth with radon levels revealed that wells drilled in Saq aquifer consisting of predominantly sandstone with significant shale layers in the upper parts, gave higher median radon levels than in Manjur aquifer which consists of predominantly limestone and sandstone.


Prevalence and sociodemographic correlates of diabetes among adults in Namibia and South Africa.
The aims of this study were to understand the prevalence and sociodemographic characteristics associated with diabetes among adults in Namibia and South Africa. Data from the Demographic and Health Survey for Namibia (2013) and South Africa (2016) were analyzed. The dependent variable, diabetes, was defined using lab values for blood glucose≥ 126 for Namibia, and hemoglobin A1c (HbA1c) ≥ 6.5% for South Africa. Logistic regression was used to identify independent correlates of diabetes for each country. Demographic (age, sex, geographic location, number of children), economic (wealth index, education level), and cultural (religion - Namibia, ethnicity - South Africa) factors were added in blocks to the models. In Namibia, 4.6% had diabetes based on blood glucose, and 14.6% had diabetes based on HbA1c in South Africa. In Namibia, after adjustment, higher wealth was independently associated with diabetes (OR:1.67; 95% CI: 1.11, 2.50). In South Africa, after adjustment, those who were older (OR: 1.06; 95% CI: 1.04, 1.07), female (OR: 1.25; 95% CI: 1.03, 1.52), lived in a rural area (OR: 1.54; 95% CI: 1.20, 1.96), and Black (OR: 2.27; 95% CI: 1.17, 4.42) or Other (OR: 5.74; 95% CI: 2.50, 13.20) compared to White, had increased odds of diabetes. Prevalence of diabetes is high in South Africa and relatively low in Namibia using reliable laboratory diagnostic indices. Strategies to address the rising burden of non-communicable diseases like diabetes are needed in sub-Saharan Africa.


Augmented antiviral T cell immunity by oral administration of IMM-124E in preclinical models and a phase I/IIa clinical trial: A method for the prevention and treatment of COVID-19.
Biological adjuvants that target the gut immune system are being developed for modulating the immune system. Hyperimmune bovine colostrum (HBC), produced by harvesting the bovine colostrum of dairy cows immunized to exogenous antigens, has been shown to modulate the immune responses and alleviate immune-mediated organ damages. The aim of the present study was to determine the ability of HBC to promote antiviral interferonγ (IFNγ) T cell responses. In a preclinical study, mice were orally administered with HBC for 5 days and tested for the number of T cell clones secreting IFNγ in response to viral antigens of the swine flu, New Caledonia influenza, and cytomegalovirus. In a phase I/IIa clinical trial, five healthy volunteers were treated for 5 days with HBC followed by testing the anti-coronavirus disease (COVID-19) immunity. In the preclinical study, oral administration of HBC augmented the number of T cell clones secreting IFNγ in response to viral antigens. In the clinical trial, oral administration of HBC to healthy males significantly increased the number of anti-COVID-19 spike protein IFNγ positive T cell clones. Oral administration of HBC provides a novel method for augmenting antiviral responses. Its high-safety profile makes it ideal for all disease stages and for pre-emptive therapy among medical personnel and other workers who are at a high risk of exposure to infections. The relatively low cost of HBC is expected to minimize care provider burdens, costs, and enable its global application.


Cytokimera GIL-11 rescued IL-6R deficient mice from partial hepatectomy-induced death by signaling via non-natural gp130:LIFR:IL-11R complexes.
All except one cytokine of the Interleukin (IL-)6 family share glycoprotein (gp) 130 as the common β receptor chain. Whereas Interleukin (IL-)11 signal via the non-signaling IL-11 receptor (IL-11R) and gp130 homodimers, leukemia inhibitory factor (LIF) recruits gp130:LIF receptor (LIFR) heterodimers. Using IL-11 as a framework, we exchange the gp130-binding site III of IL-11 with the LIFR binding site III of LIF. The resulting synthetic cytokimera GIL-11 efficiently recruits the non-natural receptor signaling complex consisting of gp130, IL-11R and LIFR resulting in signal transduction and proliferation of factor-depending Ba/F3 cells. Besides LIF and IL-11, GIL-11 does not activate receptor complexes consisting of gp130:LIFR or gp130:IL-11R, respectively. Human GIL-11 shows cross-reactivity to mouse and rescued IL-6R-/- mice following partial hepatectomy, demonstrating gp130:IL-11R:LIFR signaling efficiently induced liver regeneration. With the development of the cytokimera GIL-11, we devise the functional assembly of the non-natural cytokine receptor complex of gp130:IL-11R:LIFR.


Physical activity in women: current guidelines and strategies for promoting compliance.
The benefits of physical activity are significant. The risks of premature death, cardiovascular disease, strokes, diabetes mellitus, certain cancers, and cognitive impairment are decreased with moderate-intensity and vigorous-intensity physical activity. Guidelines have been published by the American College of Sports Medicine, American Heart Association, and US Department of Health and Human Services. The availability of pedometers has popularized step-based programs. Unfortunately, compliance with these guidelines is poor. Physical activity counseling should be a part of every woman's health maintenance encounter. The 5 A's consisting of assess, advise, agree, assist, and arrange can be effective in increasing physical activity.


Incremental benefit of 3D transesophageal echocardiography: a case of a mass overlying a prosthetic mitral valve.
A young woman with a mechanical mitral valve and prosthetic mitral stenosis underwent multiple imaging modalities (including transthoracic ECHO, fluoroscopy, and two-dimensional transesophageal ECHO) to determine the cause of her stenosis. Only three-dimensional transesophageal echocardiography demonstrated the full size and extent of an obstructing mass on the strut and sewing ring of the prosthetic mitral valve.


Mesothelial stomata overlying omental milky spots: scanning electron microscopic study.
The presence in the rat omentum of intercellular pores (the classical stomata of von Recklinghausen) between the mesothelial cells overlying aggregates of lymphoreticular cells (the classical milky spots of Ranvier) and the apparent migration of lymphocytes through these stomata were recorded for the first time by scanning electron microscopy. Previous studies on passage of cells across the peritoneum and omentum used experimentally administered cells, while in the present study no cells were administered to the rats and their own lymphocytes were observed in situ. The possible role of lymphocytes in the peritoneal cavity is also briefly discussed.


Manganese-induced single strand breaks of mitochondrial DNA in vitro and in vivo.
The aim of this study was to examine the single strand breaks (SSB) of mitochondrial DNA (mtDNA) induced by MnCl(2) in vitro and in vivo and discuss the possible underlying mechanism. In in vitro study the formation of mtDNA SSB and reactive oxygen species (ROS) in isolated hepatic mitochondria treated with MnCl(2) (0-1.0mmolL(-1)) was observed. In in vivo study the SSB of brain and liver mtDNA was examined, meanwhile the level of glutathione (GSH) and malondialdehyde (MDA) and activity of antioxidant enzymes were examined after 3-month intraperitoneal administration of MnCl(2) daily (0, 5, 10 and 20mg/kg/d) in Sprague-Dawley rats. The in vitro results indicated that MnCl(2) increased the formation of mtDNA SSB and ROS in **a dose-dependent manner in vitro. MnCl(2) exposure in vivo increased in mtDNA SSB in rat brain and liver and decreased in level of GSH in rat hepatic mitochondria and brain homogenates in a dose-dependent manner. The level of MDA and the activities of SOD and GPx were not significantly changed in both hepatic mitochondria and brain homogenates of rats. These results indicated that Mn treatment increased in mtDNA SSB in vitro and in vivo, mediated probably via Mn-induced oxidative stress.


[Results of therapy of acute mesenteric vascular occlusion].
From 1979 to 1984 39 patients were operated on for acute mesenteric ischemia. The purpose of this retrospective study was the documentation of the therapeutic results and discussion of the value of a second-look operation and postoperative angiography. Proximal occlusion of SMA in 33 patients (85%) resulted in extended bowel infarction, whereas segmental infarction due to peripheral occlusion was found in 15%. The hospital mortality was 85%. Operative procedure consisted of revascularisation (18%), bowel resection (18%), revascularisation and resection (10%) and explorative laparotomy (18%). The second-look operation as a routine procedure has been replaced by a postoperative angiogram. Laparotomy was performed in case of reocclusion of SMA or clinical signs.


Effect of nitrous oxide (N2O) on the structure and function of nitrogen-oxide reducing microbial communities.
Nitrous oxide (N2O) is a potent greenhouse gas that can be produced by nitrifying and denitrifying bacteria. Yet the effects of N2O on microbial communities is not well understood. We used batch tests to explore the effects of N2O on mixed denitrifying communities. Batch tests were carried out with acetate as the electron donor and with the following electron acceptors: nitrate (NO3-), nitrite (NO2-), N2O, NO3- + N2O, and NO2- + N2O. Activated sludge from a municipal wastewater treatment plant was used as the inoculum. The bacteria grew readily with N2O as the sole acceptor. When N2O was provided along with NO3- or NO2-, it was used concurrently and resulted in higher growth rates than the same acceptors without added N2O. The microbial communities resulting from N2O addition were significantly different at the genus level from those with just NO3- or NO2-. Tests with N2O as the sole added acceptor revealed a reduced diversity. Analysis of inferred gene content using PICRUSt2 indicated a greater abundance of genera with a complete denitrification pathway when growing on N2O or NO2-, relative to all other tests. This suggests that specific N2O reduction rates are high, and that N2O alone selects for a low-diversity, fully denitrifying community. When N2O is present with NO2- or NO3-, the microbial communities were more diverse and did not select exclusively for full denitrifiers. N2O alone appears to select for a "generalist" community with full denitrification pathways and lower diversity. In terms of denitrification genes, the combination of acceptors with N2O appeared to increase the number of microbes carrying nirK, while fully denitrifying bacteria appear more likely to carry nirS. Lastly, all the taxa in NO2- and N2O samples were predicted to harbor nosZ. This suggests the potential for reduced N2O emissions in denitrifying systems.


Giant right coronary artery aneurysm.
We report the case of a 59-year-old man with a giant atherosclerotic thrombus-filled aneurysm of the right coronary artery presenting as an ambiguous spherical mass adjacent to the right atrium at the transthoracic echocardiography study. The diagnosis was established by transesophageal echocardiography, computed tomography, and coronary angiography. Due to extent of the aneurysm, the patient underwent placement of a vein graft to the posterior descending artery and subsequent exclusion of the aneurysm by proximal and distal ligation.


Isolation and analysis of two naturally-occurring multi-recombination Newcastle disease viruses in China.
Two Newcastle disease viruses (NDV), designated QG/Hebei/07 and XD/Shandong/08, were isolated from infected chicken flocks in China in 2007 and 2008, respectively. The results of phylogenetic and recombination analyses on complete NDV genome sequences (excluding terminal segments) show that the QG/Hebei/07 isolate had evidence of recombination in the M and F genes, and recombination in the XD/Shandong/08 isolate in the F, L genes and the non-coding region between the HN and L genes. These two naturally-occurring recombinants we found to be descended from at least three putative parents from vaccine and circulating virus lineages. Moreover, we found that evidence that homologous recombination also occurred between NDV viruses of chicken and swine lineages, while the major putative parent is likely to have been derived from the chicken avirulent vaccine lineage. This study suggests that homologous recombination can occur in all coding and non-coding regions of the NDV genome and a live vaccine strain is capable of recombination with circulating viruses resulting in significant genetic change. The potential role of swine-origin viruses in the evolution of virulent NDV warrants further investigation.


Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid.
Magnetic nanoparticles show great promise for use as tools in a wide variety of biomedical applications. The purpose of this study was to investigate the potential effects of methacrylamido-folic acid (Ma-Fol)-modified magnetic nanoparticles on 5RP7 (H-ras-transformed rat embryonic fibroblasts) and NIH/3T3 (normal mouse embryonic fibroblasts). The cytotoxicity and viability of 5RP7 and NIH/3T3 cells were detected. The percentage of cells undergoing apoptosis was analyzed by flow cytometry using Annexin V-fluorescein isothiocyanate staining. Nanoparticle internalization into 5RP7 and NIH/3T3 cells was visualized by transmission electron microscopy. In this study, folic acid coupled to the surface of iron oxide for selective binding to cancer cells and immobilized the surfaces of magnetic nanoparticles. This complex improves cell internalization and targeting of cancer cells. We detected increased apoptosis using flow cytometry and transmission electron microscopy. Folic acid modification of magnetic nanoparticles could be used to facilitate uptake to specific cancer cells for cancer therapy and diagnosis. Our results showed that the uptake of folic-acid modified nanoparticles by 5RP7 cancer cells was also much higher than that of 3T3 cells. This modification can be used for successful targeting of cancer cells expressing the folate receptor.


Analysis of the strategies used by iranian nurses for management of provided care for patients with COVID- 19: a qualitative study.
Nurses have been at the center of managing the COVID-19 outbreak through direct bedside care in respiratory, emergency and intensive care environments, managing hospital units, providing Covid-19 testing, vaccination and contact tracing. Thus, the present study aimed to analysis the strategies used by Iranian nurses for management of Provided Care for patients with COVID- 19. The present study was conducted based on the conventional content analysis method and Graneheim & Lundman approach. The participants included the nurses working in the COVID-19 wards and were recruited by purposeful sampling and based on inclusion criteria. The data were collected by conducting semi-structured, in-depth, one-to-one interviews until reaching data saturation. In-depth interviews with 10 nurses represented four main categories and fifteen subcategories. Four main categories emerged in this study i.e. "justice in human resources management", "The art and science of comprehensive nursing care", "managers as agents of change in crisis" and "challenges and its management". The nurses' experiences of management strategies showed that paying attention to the financial, psychological, educational, equipment needs of nurses and maintaining their safety make the suitable environment for providing high quality care for patients with covid-19.


Transcatheter embolization of a renal artery pseudoaneurysm after open partial nephrectomy.
Twelve days after an open partial nephrectomy, a 31-year-old man was re-admitted urgently for acute lumbar pain. An emergent helical computed tomography scan with intravenous contrast revealed a 3-cm renal artery pseudoaneurysm at the site of the partial nephrectomy, which was responsible for a large perirenal hematoma. Transarterial hyperselective embolization successfully occluded the pseudoaneurysm with less than 1 mL of N-butyl-2-cyanoacrylate, an embolizing agent less costly than coils. The kidney parenchyma was fully preserved.


Identification of membrane progestin receptors (mPR) in goldfish oocytes as a key mediator of steroid non-genomic action.
One of the most extensively investigated and well characterized models of non-genomic steroid actions initiated at the cell surface is the induction of oocyte maturation (OM) in fish and amphibians by progestin. Gonadotropin induces the final phase of oocyte maturation indirectly by inducing the synthesis of maturation inducing steroids (MIS) by the ovarian follicles via its membrane receptor, membrane progestin receptor (mPR). Three mPR subtypes (α, β and γ) have been identified by cDNA cloning or by in silico analysis of genome sequence databases. Previously, we described the cloning of the mPRα cDNA from a goldfish ovarian cDNA library and obtained experimental evidence that the mPRα protein is an intermediary in MIS induction of OM in goldfish. Then we cloned one β and two γ subtypes (hereafter referred to as γ-1 and γ-2) from a goldfish ovarian cDNA library. RT-PCR showed different tissue expression patterns of the mRNAs for these mPR subtypes. However, in addition to mPRα, the β, γ-1 and γ-2 subtypes were also expressed in follicle-enclosed oocytes. Microinjection of goldfish oocytes with a morpholino antisense oligonucleotide to mPRβ blocked the induction of oocyte maturational competence, whereas injection of antisense oligonucleotides to mPRγ-1 and γ-2 were ineffective. These results suggest that goldfish mPRβ protein acts as an intermediary during MIS induction of OM in goldfish, in a manner similar to mPRα. We are establishing mutant strains of Medaka fish to investigate the roles of mPR proteins in vivo produced by Targeting Induced Local Lesions in Genomes (Tilling) strategy. By the screening, we have selected three strains in which a point mutation was induced in each strain at the coding sequence of mPRα. In near future results of phenotypic analysis of mPRα defective fish will be introduced.


Neuroglobin, cytoglobin, and a novel, eye-specific globin from chicken.
Neuroglobin and cytoglobin are two recently discovered respiratory proteins of vertebrates. Here we report the first identification and expression analyses of these proteins in bird species. Neuroglobin from the domestic chicken Gallus gallus differs in approximately 30% from the mammalian proteins, but its genome structure shows the conservation of the B12.2, E11.0, and G7.0 intron positions. The chicken cytoglobin protein is shorter than the mammalian orthologs, from which it differs overall by approximately 25%, due to the absence of the C-terminal exon in the gene. Comparison of chicken and mammalian gene order shows that neuroglobin and cytoglobin are located on conserved syntenic chromosomal segments. While neuroglobin is expressed in the chicken's brain and eye, cytoglobin RNA was detected in all investigated tissues. In addition, a novel globin-type has been identified that is only expressed in the chicken's eye. The gene of this eye-globin contains the typical globin introns at B12.2 and G7.0. Phylogenetic analyses suggest that this globin is most closely related to the cytoglobin lineage. Although the function of this eye-globin remains presently uncertain, it adds an additional diversity to the vertebrate globin family.


The binding of a transcription factor to deletion mutants of a 5S ribosomal RNA gene.
A transcription factor binds specifically to a region within the 5S ribosomal RNA gene that is known to be required for accurate initiation of transcription of the gene. We have confirmed the significance of this interaction by comparing various deletion mutants for their ability to initiate transcription and to bind the protein. Loss of specific binding of the protein occurs when the gene is deleted beyond +83 from the 3' direction. This coincides exactly with the loss of ability to initiate transcription. In contrast, deletions entering the gene from the 5' direction and extending beyond the 5' border of the control region (+50/+55) give partial protection of the remainder of the control region. This observation can explain why deletions beyond the 5' border of the control region that are unable to initiate transcription can still compete for the transcription of the wild-type 5S RNA gene.


Trans-obturator colonic suspension during Altemeier's operation for full-thickness rectal prolapse: preliminary results with a new technique.
With the aim of reducing recurrence after perineal surgery for full-thickness rectal prolapse, a new operation consisting of a trans-obturator colonic suspension during Altemeier's operation has been developed. Eighteen women with full-thickness rectal prolapse were examined clinically, with validated quality of life and continence scores, colonoscopy, anorectal manometry, anal EMG and sacral reflex latency. Ten had a newly diagnosed and eight a recurrent prolapse. The Altemeier operation was combined with a levatorplasty in all cases using two porcine collagen prostheses sutured to the descending colon and passed through the trans-obturator space bilaterally. The operation was completed by a manual or stapled colo-anal anastomosis. Clinical examination, with quality of life and continence scores, anorectal manometry, EMG and sacral reflex latency, was scheduled during follow up, with the recurrence of prolapse as the primary outcome measure. There were no recurrences at 30 months. There was no mortality and no complications. All patients experienced significant improvement in quality of life and faecal continence scores (P<0.01). Surgery did not affect anorectal pressures or sacral reflex latencies. The new technique appears to be relatively easy to perform and is complication free with no recurrence after a short period of follow up. A larger study with appropriate controls and longer follow up is now needed to assess its real effectiveness in reducing the risk of recurrence.


The importance of dietary protein in healing pressure ulcers.
To determine the effect of dietary protein on healing of pressure ulcers in malnourished patients. Nutritional intervention trial with the non-randomized assignment of patients by pressure ulcer stage and bed type. Long-term care facility. Twenty-eight malnourished patients (age = 72 +/- 18 years, mean +/- SD) with a total of 33 truncal pressure ulcers. Nine patients had stage II ulcers, eight had stage III ulcers, and 16 had stage IV ulcers. Patients received liquid nutritional formulas as tubefeedings or meal supplements containing either 24% protein (61 g protein/L; n = 15) or 14% protein (37 g protein/L; n = 13) for 8 weeks. There was a significant decrease in total truncal pressure ulcer surface area of the 15 patients in the 24% protein group (-4.2 +/- 7.1 cm2, P < 0.02), but not in the 13 patients in the 14% protein group (-2.1 +/- 11.5 cm2, P = NS). The change in total ulcer area correlated with both dietary protein intake per kg body weight (rs = -0.50, P < 0.01) and caloric intake per kg body weight (rs = -0.41, P < 0.03). The decrease in stage IV ulcer area in eight patients in the 24% protein group (-7.6 +/- 5.8 cm2, P < 0.02) was significantly greater (P < 0.05) than in eight patients in the 14% protein group (-3.2 +/- 16.4, P = NS). In these 16 patients, the decrease in ulcer size also correlated with dietary protein intake per kg body weight (rs = -0.63, P < 0.01). High protein diets may improve the healing of pressure ulcers in malnourished nursing home patients.


Reduction of taxonomic bias in diatom species data.
Inconsistency in taxonomic identification and analyst bias impede the effective use of diatom data in regional and national stream and lake surveys. In this study, we evaluated the effect of existing protocols and a revised protocol on the precision of diatom species counts. The revised protocol adjusts five elements of sample preparation, taxon identification and enumeration, and quality control (QC) samples. We used six independent datasets to assess the effect of the adjustments on analytical outcomes. The first dataset was produced by five analysts from three laboratories following a standard protocol (Charles et al. 2002). The remaining datasets were produced by 2-3 analysts in 1-3 laboratories following a revised protocol. The revised protocol included the following modifications: 1) use of Battarbee settling chambers to prepare coverslips, 2) development of coordinated pre-count voucher floras based on morphological operational taxonomic units (mOTUs), 3) random assignment of samples to analysts, 4) post-count identification and documentation of taxa, and 5) increased QC samples. The revised protocol reduced taxonomic bias, as measured by reduction in analyst signal, and improved similarity among QC samples. Reduced taxonomic bias improves the performance of biological assessments, facilitates transparency across studies, and refines estimates of diatom species distributions.


Characterising Negative Mental Imagery in Adolescent Social Anxiety.
Understanding the role of self-imagery in the development of social anxiety in adolescence holds promise for improving intervention. Cross-sectional studies indicate that imagery characteristics are associated with social anxiety symptoms, however, prospective studies are lacking. The current study examined concurrent and prospective associations between two image characteristics, namely observer-perspective and vividness, with social anxiety symptoms in a community adolescent sample (N = 616; 53% girls; aged 11-15 years). In addition, we examined common themes in the negative social anxiety-related images. Negative self-imagery and social anxiety symptoms were assessed using questionnaires at baseline and at 4-6-month follow-up. A series of multiple linear regression analyses were performed to see if each image characteristic predicts concurrent and prospective social anxiety symptoms. Topic modelling was performed to infer key topics from verbal data. Observer-perspective and vividness significantly predicted concurrent social anxiety symptoms beyond the influence of age and gender. Observer-perspective significantly predicted prospective levels of social anxiety symptoms beyond the influence of age, gender, and baseline social anxiety and depression symptoms. Negative self-images clustered into two themes: the fear of appearing anxious and the fear of being judged or viewed as unacceptable. Specific characteristics and contents of negative self-images may be particularly relevant to the development of adolescent social anxiety. The online version contains supplementary material available at 10.1007/s10608-022-10316-x.


Effects of estrogen on proton secretion via the apical membrane in vaginal-ectocervical epithelial cells of postmenopausal women.
To understand estrogen regulation of proton (H(+)) secretion by human vaginal-ectocervical epithelial cells and the mechanisms involved. Primary-tertiary cultures of human normal vaginal-ectocervical epithelial cells were generated from surgical specimens of premenopausal women (aged 37-46 years) and of postmenopausal women (aged 53-65 years). Cells were grown on filters, and measurements were made of changes in extracellular pH (pHo) in the contraluminal (CL) and luminal (L) solutions 30 minutes after shifting cells to basic salt solution. Upon shifting cells to basic salt solution, CL-pHo decreased from 7.4 to 7.25, and was not affected by removal of intracellular estrogens or treatment with estradiol. L-pHo decreased from 7.4 to 7.05 in cells of premenopausal women, and from 7.4 to 7.20 in cells of postmenopausal women. Removal of intracellular estrogens attenuated the decrease in L-pHo in cells of premenopausal women (only to 7.20). In cells of premenopausal women stripped of estrogens, treatment with 10 nM 17beta-estradiol restored the decrease in L-pHo. In estrogen-stripped cells of postmenopausal women, treatment with estradiol augmented luminal acidification but to a lesser degree than in cells of premenopausal women (L-pHo of 7.15 vs 7.05). In cells of pre- and postmenopausal women, the addition in the L solution of bafilomycin-A(1), a specific inhibitor of the vacuolar-H(+)-ATPase (V-H(+)-ATPase), blocked the decrease in L-pHo. Human vaginal-ectocervical epithelial cells acidify constitutively their luminal solution, and the effect is mediated by active H(+) secretion by V-H(+)-ATPase expressed predominantly in the apical cell membrane. Estrogen deprivation attenuates, and treatment with 17beta-estradiol augments, active H(+) secretion. Finally, cells of postmenopausal women actively secrete H(+) via apically located V-H(+)-ATPase, but the effect is lesser, and estrogen failed to augment active H(+) secretion, as in cells of premenopausal women. These data suggest that in addition to hypoestrogenism, other factors of the aging process affect the capacity of vaginal-ectocervical cells to secrete acid.


Model averaging using the Kullback information criterion in estimating effective doses for microbial infection and illness.
Since the National Food Safety Initiative of 1997, risk assessment has been an important issue in food safety areas. Microbial risk assessment is a systematic process for describing and quantifying a potential to cause adverse health effects associated with exposure to microorganisms. Various dose-response models for estimating microbial risks have been investigated. We have considered four two-parameter models and four three-parameter models in order to evaluate variability among the models for microbial risk assessment using infectivity and illness data from studies with human volunteers exposed to a variety of microbial pathogens. Model variability is measured in terms of estimated ED01s and ED10s, with the view that these effective dose levels correspond to the lower and upper limits of the 1% to 10% risk range generally recommended for establishing benchmark doses in risk assessment. Parameters of the statistical models are estimated using the maximum likelihood method. In this article a weighted average of effective dose estimates from eight two- and three-parameter dose-response models, with weights determined by the Kullback information criterion, is proposed to address model uncertainties in microbial risk assessment. The proposed procedures for incorporating model uncertainties and making inferences are illustrated with human infection/illness dose-response data sets.


TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis.
Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12-1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15-1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16-1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05-1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04-1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10-1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.


The information needs of women who have undergone breast reconstruction. Part II: Information giving and content of information.
Women diagnosed with breast cancer treated by mastectomy can choose breast reconstruction. The information needs of women undergoing this procedure have only been addressed in the research literature to a limited extent. A qualitative approach was used to explore the experiences of women who had undergone breast reconstruction with a specific focus on their views on how they considered their information needs could best be met. A purposeful sample of eight women was recruited to participate in two focus groups, each lasting 2 hours. Framework analysis was used to develop an index of key themes and sub themes which transformed the data into a structured record which facilitated systematic analysis. This paper will present the emergent key themes regarding information giving and the content of information that women perceive as important when preparing for breast reconstruction. Process, delivery and patient factors are presented in the category of information giving. Several sub themes are discussed concerning the content of information considered to be relevant. Those involved in imparting information to women about such surgery should be aware of the type of information that is considered relevant, the manner in which it should be delivered and timing factors that implicate on the process.


Antegrade pyelography: therapeutic applications.
Antegrade pyelography is a diagnostic examination that is easily converted for therapy in the urinary tract. The applications of the antegrade approach discussed in this article include drainage in obstruction and fistulas, access for manipulations, and topical treatment.


Diagnostic value of cardiac natriuretic peptide on pulmonary hypertension in systemic sclerosis: A systematic review and meta-analysis.
Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in systemic sclerosis (SSc). Many risk factors and predictors of outcomes have been identified in these patients. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) serum levels are often elevated in SSc patients with early PAH. We conducted this systematic review and meta-analysis to estimate the diagnostic value of BNP/NT-proBNP in systemic sclerosis secondary pulmonary arterial hypertension (SSc-PAH). A systematic search was performed through PubMed, Embase, and Cochrane Library databases up to January 30, 2021. Stata 16.0 (Stata Corp, College Station, TX) was used to conduct the meta-analysis. A total of 9 studies involving 220 SSc-PAH patients and 259 non-SSc-PAH controls were included. The values of sensitivity and specificity using BNP and NT-ProBNP as diagnostic tools were pooled in the diagnostic meta-analysis. The overall performance of BNP/NT-ProBNP detection was: pooled sensitivity, 0.67 (95% CI: 0.52 to 0.79); pooled specificity, 0.84 (95% CI: 0.75 to 0.91); pooled positive likelihood ratio, 4.3 (95% CI: 3 to 6.1); and pooled negative likelihood ratio, 0.39 (95% CI: 0.28 to 0.55). The subgroup analysis showed similar results. Funnel plots indicate that there is no evidence for publication bias. Our results revealed that NT-proBNP has certain diagnostic value for PAH due to its better specificity and moderate sensitivity, but its clinical application value remains suboptimal and can not be a stand-alone decision-making diagnostic tool of SSc-PAH.


Pharmacological interventions for preventing atrial fibrillation after lung surgery: systematic review and meta-analysis.
Postoperative atrial fibrillation/flutter (POAF) is one of the most common cardiac complications after lung surgery. We aimed to assess the safety and efficacy of pharmacological interventions for new-onset POAF prophylaxis in patients with lung cancer after lung surgery. PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were searched to identify randomized controlled trials comparing the effects of pharmacological interventions to prevent POAF following lung surgery. A total number of 19 studies with 2,922 participants were included. Pharmacological interventions significantly reduced the incidence of POAF (odds ratio [OR] 0.36, 95% confidence interval [95% CI] 0.26-0.52) while did not increase the incidence of severe pulmonary complications (OR 1.17, 95% CI 0.57-2.41) after lung surgery compared with placebo/usual care. Among different trials, beta-blockers appeared to be the most effective with an OR of 0.13 (95% CI, 0.07-0.27) and a number needed-to-treat (NNT) of 3.63 and was considered safe with no serious adverse events recorded. The risk of POAF decreased from 25.6 to 11.4% (P < 0.001) overall and from 34.2 to 6.7% (P < 0.001) with beta-blockers as monotherapy. Pharmacological interventions did not reduce the 30-day mortality (OR 0.89, 95% CI 0.43-1.84, I2 = 0%), but showed a trend toward reducing major cardiovascular complications including myocardial ischemia/infarction, cardiac arrest, heart failure, and stroke (OR 0.41, 95% CI 0.13-1.29, I2 = 0%). Current clinical evidence supports the effectiveness of pharmacological intervention with beta-blockers, amiodarone, magnesium sulfate, or calcium-channel blockers to reduce the incidence of POAF after lung surgery in patients with lung cancer. In the absence of contraindications, prophylaxis with beta-blockers seems to be the most effective of the treatments studied.


Structural and functional analysis of disease-associated mutations in GOT1 gene: An in silico study.
Disease-associated single nucleotide polymorphisms (SNPs) alter the natural functioning and the structure of proteins. Glutamic-oxaloacetic transaminase 1 (GOT1) is a gene associated with multiple cancers and neurodegenerative diseases which codes for aspartate aminotransferase. The present study involved a comprehensive in-silico analysis of the disease-associated SNPs of human GOT1. Four highly deleterious nsSNPs (L36R, Y159C, W162C and L345P) were identified through SNP screening using several sequence-based and structure-based tools. Conservation analysis and oncogenic analysis showed that most of the nsSNPs are at highly conserved residues, oncogenic in nature and cancer drivers. Molecular dynamics simulations (MDS) analysis was performed to understand the dynamic behaviour of native and mutant proteins. PTM analysis revealed that the nsSNP Y159C is at a PTM site and will mostly affect phosphorylation at that site. Based on the overall analyses carried out in this study, L36R is the most deleterious mutation amongst the aforementioned deleterious mutations of GOT1.


A Comparison of COVID-19 Outcomes Between Reservation-Area American Indian and U.S. National Students.
This study presents data from 2 population-based surveys of youth (reservation-area American Indian adolescents and U.S. adolescents) on self, family, and friend morbidity and changes in substance use and negative impacts during COVID-19. Data were obtained in spring 2021 from surveys of American Indian students living on or near reservations (8th grade, n=398; 10th grade, n=367; 12th grade, n=290) and national students from Monitoring the Future (8th grade, n=11,446; 10th grade, n=11,792; 12th grade, n=9,022). The main outcomes were COVID-19 testing, perceived morbidity/mortality, substance-use changes, and emotional changes during COVID-19. The American Indian sample had a greater proportion of testing (e.g., American Indian 8th grade: 58.1% [95% CI=48.6, 68.8]; Monitoring the Future 8th grade: 43.6% [95% CI=39.8, 47.5]) and friend/family hospitalization (e.g., American Indian 8th grade: 36.2% [95% CI=26.2, 47.5]; Monitoring the Future 8th grade: 11.9% [95% CI=10.6, 13.3]). Across grades, greater proportions of the national sample reported increased anxiety, anger, boredom, loneliness, depression, worry, and trouble concentrating, whereas greater proportions of reservation-area American Indians reported decreased anxiety, loneliness, and depression. Findings indicate that reservation-area American Indian youth experienced unique health consequences 1 year into the COVID-19 pandemic compared with national students, illustrating the need for American Indian-specific COVID-19 public health monitoring and response.


Condylar haemangioma--a case report and review of the literature.
A case of central haemangioma of the mandibular condyle is presented. A review of the literature emphasises the rarity of this benign tumour in the condylar region.


Association between immigrant status and advanced cancer patients' location and quality of death.
Cancer patients often prefer to die at home, a location associated with better quality of death (QoD). Several studies demonstrate disparities in end-of-life care among immigrant populations in the United States. This study aimed to evaluate how immigrant status affects location and quality of death among patients with advanced cancer in the United States. Data were derived from Coping with Cancer, a federally funded multi-site prospective study of advanced cancer patients and caregivers. The sample of patients who died during the study period was weighted (Nw = 308) to reduce statistically significant differences between immigrant (Nw = 49) and nonimmigrant (Nw = 259) study participants. Primary outcomes were location of death, death at preferred location, and poor QoD. Analyses adjusted for covariates indicated that patients who were immigrants were more likely to die in a hospital than home (adjusted odds ratio [AOR], 3.33; 95% confidence interval [CI], 1.65-6.71) and less likely to die where they preferred (AOR, 0.42; 95% CI, 0.20-0.90). Furthermore, immigrants were more likely to have poor QoD (AOR, 5.47; 95% CI, 2.70-11.08). Immigrants, as compared to nonimmigrants, are more likely to die in hospital settings, less likely to die at their preferred location, and more likely to have poor QoD. Cancer patients typically prefer to die in their own homes, which is associated with improved quality of death. However, disparities in end-of-life care among immigrant populations in the United States remain significant. Our study found that immigrants are less likely to die in their preferred locations and more likely to die in hospital settings, resulting in poorer quality of death.


Automated, semi-automated, and manual analyses of anti-cardiolipin and anti-β2-glycoprotein I antibodies in women with a history of miscarriage.
Anti-cardiolipin and β2-glycoprotein I antibodies represent important diagnostic parameters in routine hematology. In this study, five different automated, semi-automated, and manual immunoassays detecting IgG/IgM anti-cardiolipin and anti-β2 -glycoprotein I antibodies were tested. A total of 162 samples from women with a history of miscarriage were recruited from 110 different G&O outpatient centers in Germany. For both anti-cardiolipin and anti-β2 -glycoprotein I antibodies, considerable differences in the percentage of positive results were seen between all five methods, and itemization of all positive test results revealed a poor accordance. These findings were confirmed by Cohen's kappa coefficients. Our study revealed a moderate to poor accordance between five different test systems for anti-cardiolipin and anti-β2 -glycoprotein I antibodies. Such deviations may result in clinical misinterpretation of data and may lead to wrong therapeutic consequences. Therefore, further standardization of all tests for anti-phospholipid antibodies should be achieved.


Cross-cultural Adaptation and Validation of the Greek Voice Handicap Index-10 (GVHI-10) With Additional Receiver Operating Characteristic Analysis.
The use of subjective evaluation tools are proven useful and of high clinical value in the case of voice disordered population. For that type of evaluation, self-assessment questionnaires about the severity of the voice like Voice Handicap Index-30 (VHI-30) have been developed. The VHI-30 is the most studied tool which includes psychometrically robustness while guiding physician's therapeutic decision making. Additionally, a valid abbreviated version of VHI-30 was developed for the first time in the Greek Language which is named as Greek Voice Handicap Index-10 (GVHI-10). Consequently, the aim of our study was to validate the proposed version of the VHI-10. Ninety nondysphonic individuals and 90 dysphonic patients were classified by Otolaryngologists and Speech Language Pathologists. The study's subjects were evaluated with endoscopy and stroboscopy. Also, they were administrated the GVHI-30 and the translated version of the Voice Evaluation Template (VEF). The GVHI-10 was extracted by the Greek version of VHI-30. The group with voice disorders exhibited higher statistical significance in all GVHI-10 scores compared to those of the control group. The GVHI-10 showed a high internal consistency (Cronbach's a = 0.915 and split-half reliability coefficient equal to 0.86), good sensitivity compared to Greek VHI-30 (r = 0.764, P = 0.000) and intraclass correlation. A total cut-off point equal to 6.50 (AUC: 0.964; P < 0.001) was also calculated. The proposed version of GVHI-10 distinguished the perceived levels of voice between dysphonic and nondysphonic groups and between different voice disordered populations. The GVHI-10 is shown to be clinically valid and sensitive exhibiting high reliability.


A New Approach for Noise Suppression in Cochlear Implants: A Single-Channel Noise Reduction Algorithm.
The cochlea "translates" the in-air vibrational acoustic "language" into the spikes of neural "language" that are then transmitted to the brain for auditory understanding and/or perception. During this intracochlear "translation" process, high resolution in time-frequency-intensity domains guarantees the high quality of the input neural information for the brain, which is vital for our outstanding hearing abilities. However, cochlear implants (CIs) have coarse artificial coding and interfaces, and CI users experience more challenges in common acoustic environments than their normal-hearing (NH) peers. Noise from sound sources that a listener has no interest in may be neglected by NH listeners, but they may distract a CI user. We discuss the CI noise-suppression techniques and introduce noise management for a new implant system. The monaural signal-to-noise ratio estimation-based noise suppression algorithm "eVoice," which is incorporated in the processors of Nurotron® EnduroTM, was evaluated in two speech perception experiments. The results show that speech intelligibility in stationary speech-shaped noise can be significantly improved with eVoice. Similar results have been observed in other CI devices with single-channel noise reduction techniques. Specifically, the mean speech reception threshold decrease in the present study was 2.2 dB. The Nurotron society already has more than 10,000 users, and eVoice is a start for noise management in the new system. Future steps on non-stationary-noise suppression, spatial-source separation, bilateral hearing, microphone configuration, and environment specification are warranted. The existing evidence, including our research, suggests that noise-suppression techniques should be applied in CI systems. The artificial hearing of CI listeners requires more advanced signal processing techniques to reduce brain effort and increase intelligibility in noisy settings.


A randomized controlled trial of etanercept in the treatment of refractory recurrent spontaneous abortion with innate immune disorders.
To evaluate the effectiveness of etanercept in the treatment of refractory recurrent spontaneous abortion with innate immune disorders. A randomized controlled trial in patients with refractory innate immune RSA was conducted in our hospital. 188 patients were selected, all with at least 4 consecutive miscarriages and caused by innate immunity disorders. Patients were randomly allocated into 2 groups. One group (n = 95) used etanercept 25 mg per week starting from the first day after menstruation, while the other (n = 93) with placebo. Delivery of a healthy baby without malformations was regarded as the primary outcome. In etanercept group, 85 (89.47%) patients delivered a healthy baby, while in placebo group, this number was only 67 (72.04%) [P = 0.01, OR = 3.30; 95% CI(1.49~7.32)]. Significantly lower levels of TNF-α and NK cell activity were observed in gestation weeks 4-10 in etanercept group versus placebo group (P < 0.05). The results provide a proof of principle that etanercept can be an attractive therapeutic strategy for refractory innate immune RSA.


Solution NMR backbone assignments of the N-terminal Zα-linker-Zβ segment from Homo sapiens ADAR1p150.
Adenosine-to-inosine (A-to-I) editing of a subset of RNAs in a eukaryotic cell is required in order to avoid triggering the innate immune system. Editing is carried out by ADAR1, which exists as short (p110) and long (p150) isoforms. ADAR1p150 is mostly cytoplasmic, possesses a Z-RNA binding domain (Zα), and is only expressed during the innate immune response. A structurally homologous domain to Zα, the Zβ domain, is separated by a long linker from Zα on the N-terminus of ADAR1 but its function remains unknown. Zβ does not bind to RNA in isolation, yet the binding kinetics of the segment encompassing Zα, Zβ and the 95-residue linker between the two domains (Zα-Zβ) are markedly different compared to Zα alone. Here we present the solution NMR backbone assignment of Zα-Zβ from H. Sapiens ADAR1. The predicted secondary structure of Zα-Zβ based on chemical shifts is in agreement with previously determined structures of Zα and Zβ in isolation, and indicates that the linker is intrinsically disordered. Comparison of the chemical shifts between the individual Zα and Zβ domains to the full Zα-Zβ construct suggests that Zβ may interact with the linker, the function of which is currently unknown.


Hip-Sparing Equalization Procedures for Leg-Length Discrepancy After Total Hip Arthroplasty: A Retrospective Case Series.
Leg-length discrepancy (LLD) after primary THA is not uncommon. Little is known, however, about the role of hip-sparing procedures for equalization of LLD after THA. The aim of this study is to report our experiences with these techniques in patients presenting at one institution over a 10-year period. We retrospectively reviewed records at one institution to find patients who had sought surgical treatment for LLD after THA between January 2007 and August 2017. Patients who had LLD related to conditions other than the THA, such as bone loss or traumatic defects, were excluded. We recorded the time after THA, laterality, and LLD. Assessment of LLD was performed using clinical and radiographic examinations. Patient demographics and true LLD were recorded, as were prior conservative treatment, equalization procedure performed, final leg length after equalization surgery, time to healing, and complications. After exclusion of patients with LLD related to other causes, eight patients in whom conservative treatment had failed and who had undergone hip-sparing leg-length equalization surgery were included in the study. The average age was 44.6 years (range, 18 to 66 years). Seven of the patients were female. The pre-operative mean LLD was 3.1 cm (range 1.5 to 7 cm). In those who were long after THA, ipsilateral (THA-side) shortening of femur with a retrograde intramedullary nail (IMN; n = 1) or with a plate (n = 1) was performed. In those who were short after THA, ipsilateral femur lengthening with retrograde Precice nails (n = 2), ipsilateral tibial lengthening with Precice nails (n = 2), or contralateral femur shortening with a retrograde IMN (n = 2) was performed. The average time to full consolidation or union was 6.6 months (range, 2 to 19 months). Two patients had delayed union. All patients but one were satisfied with final results. We believe that hip-sparing equalization procedures can be part of the treatment algorithm of LLD after THA. These advancements in the field are promising and might expand the indications of lengthening and equalization procedures to include LLD after THA.


Assessing homeland chemical hazards outside the military gates: industrial hazard threat assessments for department of defense installations.
As part of comprehensive joint medical surveillance measures outlined by the Department of Defense, the US Army Center for Health Promotion and Preventive Medicine (USACHPPM) is beginning to assess environmental health threats to continental US military installations. A common theme in comprehensive joint medical surveillance, in support of Force Health Protection, is the identification and assessment of potential environmental health hazards, and the evaluation and documentation of actual exposures in both a continental US and outside a continental US setting. For the continental US assessments, the USACHPPM has utilized the US Environmental Protection Agency (EPA) database for risk management plans in accordance with Public Law 106-40, and the toxic release inventory database, in a state-of the art geographic information systems based program, termed the Consequence Assessment and Management Tool Set, or CATS, for assessing homeland industrial chemical hazards outside the military gates. As an example, the US EPA toxic release inventory and risk management plans databases are queried to determine the types and locations of industries surrounding a continental US military installation. Contaminants of concern are then ranked with respect to known toxicological and physical hazards, where they are then subject to applicable downwind hazard simulations using applicable meteorological and climatological data sets. The composite downwind hazard areas are mapped in relation to emergency response planning guidelines (ERPG), which were developed by the American Industrial Hygiene Association to assist emergency response personnel planning for catastrophic chemical releases. In addition, other geographic referenced data such as transportation routes, satellite imagery and population data are included in the operational, equipment, and morale risk assessment and management process. These techniques have been developed to assist military medical planners and operations personnel in determining the industrial hazards, vulnerability assessments and health risk assessments to continental United States military installations. These techniques and procedures support the Department of Defense Force Protection measures, which provides awareness of a terrorism threat, appropriate measures to prevent terrorist attacks and mitigate terrorism's effects in the event that preventive measures are ineffective.


Sodium channel blockers for the treatment of epilepsy in CDKL5 deficiency disorder: Findings from a multicenter cohort.
This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy.


Sex and Estrous Cycle Differences in Analgesia and Brain Oxycodone Levels.
Sex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle differences in analgesia (nociception) from oxycodone in rats and related these to sex and cycle differences in brain and plasma oxycodone and metabolite levels. Since numerous opioids are CYP2D enzyme substrates and variation in CYP2D alters opioid drug levels and response, we also initiated studies to see if the sex and cycle differences observed might be due to differences in brain CYP2D activity. Across oxycodone doses, females in diestrus had higher analgesia (using tail flick latency) compared to males and females in estrus; we also demonstrated a direct effect of estrous cycle on analgesia within females. Consistent with the analgesia, females in diestrus had highest brain oxycodone levels (assessed using microdialysis) compared to males and females in estrus. Analgesia correlated with brain oxycodone, but not brain oxymorphone or noroxycodone levels, or plasma drug or metabolite levels. Propranolol (a CYP2D mechanism-based inhibitor), versus vehicle pre-treatments, increased brain oxycodone, and decreased brain oxymorphone/oxycodone drug level ratios (an in vivo CYP2D activity phenotype in the brain) in males and females in estrus, but not in females in diestrus. Brain oxymorphone/oxycodone inversely correlated with analgesia. Together, both sex and estrous cycle impact oxycodone analgesia and brain oxycodone levels, likely through regulation of brain CYP2D oxycodone metabolism. As CYP2D6 is expressed in human brain, perhaps similar sex and cycle influences also occur in humans.


Increasing effect of Tangzhiqing formula on IRS-1-dependent PI3K/AKT signaling in muscle.
Tangzhiqing fomula (TZQ-F), the mixture of Red Paeony root, Mulberry leaf, Lotus leaf, Danshen root and Hawthorn leaf, regulates the abnormal glucose and lipids in prediabetic patients. In this study, we focus on the mechanism of TZQ-F and its fractions on glucose metabolism. After orally administration of TZQ-F for 4 weeks in KK-Ay mice, we dissected out the liver and muscle, and employed PCR and western blotting to screening the PI3K/AKT pathway. The following PI3K/AKT signaling pathway were performed in L-6 myotube and HepG2 cells. In the liver of KK-Ay mice, no significance was observed on PI3K, AKT and their phosphorylation between TZQ-F and controls , while, in the muscle, up-regulation of PI3K, AKT, Glycogen synthase (GYS) and their phosphorylation type, as well as GluT4, was deteced in TZQ-F. In HepG2 cells, TZQ-F increased IRS-2 by 10 folds, without interrupting AKT, IRS-1 and GluT4. In L-6 myotube cells, TZQ-F and its fractions treatment significantly increased IRS-1 and AKT at mRNA level. TZQ-F prevents pre-diabetes through increasing effect on IRS-1-dependent PI3K/AKT signaling pathway in muscle.


Validity of urine-CCA cassette test and indirect haem-agglutination assay (IHA) in the detection of schistosomiasis-mansoni infection relative to microscopic examination.
Several immunodiagnostic assays have been commercially presented over the last years as easy diagnostic methods for schistosomiasis using serum or urine samples. The performance of immunochromatographic test (ICT) and indirect hemagglutination assay (IHA) was validated in the identification of active schistosomiasis infection. Detection of circulating cathodic antigen (CCA) of the parasite in urine samples and anti-Schistosoma antibodies in serum using ICT (Urine-CCA Cassette test) and IHA respectively. Proved diagnosis of Schistosoma mansoni infection was defined by the sum of positive results from microscopic examination (Gold standard) and Kato-Katz method. Out of 173 (mean age, 45 ± 10 years; 70 from Giza, 103 from different Egyptian governorates), 9 4 adult patients were infected. Urine-CCA cassette test despite showing high specificity (91.14%) it was of low sensitivity (23.40%). PPVs was 75.86% and NPV was 50.00% and diagnostic accuracy of 54.34%. The IHA showed a sensitivity of 57.45% and specificity of 48.10%. PPVs was 56.84% whereas NPVs was 48.72%. As for diagnostic accuracy, it was 53.18%. Urine-CCA Cassette test had lower sensitivity than expected for detection of circulating antigen and the IHA kit is generally more expensive than microscopic examination and Urine-CCA cassette test with low sensitivity and specificity. On the basis of this diagnostic performance none of the two tested immune-assays can be a sole tool in the principal diagnosis of active schistosomiasis infections.


Erythrogenic toxin type A (ETA): epidemiological analysis of gene distribution and protein formation in clinical Streptococcus pyogenes strains causing scarlet fever and the streptococcal toxic shock-like syndrome (TSLS).
Erythrogenic toxin type A (ETA) is assumed to play a causative role in both scarlet fever and the streptococcal toxic shock-like syndrome (TSLS). For a molecular epidemiological analysis of the gene of erythrogenic toxin type A (speA) we used altogether 497 clinical isolates of Streptococcus pyogenes belonging to three groups: a) isolates from patients with scarlet fever, b) isolates from cases with TSLS, c) isolates from patients with other streptococcal infections (like otitis media, tonsillitis, impetigo) (general group). We found that less than 50% of the scarlet fever-associated strains possessed the speA gene as compared to 25% of the general group. Only 5 to 30% of these strains secreted the toxin under experimental conditions in very low quantities. Among strains isolated from TSLS, 67% appeared to contain the speA gene. The amount of ETA secreted into the medium was also extremely low. Southern hybridization patterns proved to be the same with an speA-specific probe in all three groups of streptococcal isolates (HaeIII, HindIII). Increased occurrence of the speA gene among scarlet fever and TSLS-associated strains does not seem to be sufficient to support the hypothesis that ETA may have a causative role in both diseases since a considerable number of strains in these groups did not possess the speA gene.


Genome Editing of Silkworms.
Silkworm is a lepidopteran insect that has been used as a model for a wide variety of biological studies. The microinjection technique is available, and it is possible to cause transgenesis as well as target gene disruption via the genome editing technique. TALEN-mediated knockout is especially effective in this species. We also succeeded in the precise and efficient integration of a donor vector using the precise integration into target chromosome (PITCh) method. Here we describe protocols for ZFN (zinc finger nuclease)-, TALEN (transcription activator-like effector nuclease)-, and CRISPR/Cas9-mediated genome editing as well as the PITCh technique in the silkworm. We consider that all of these techniques can contribute to the further promotion of various biological studies in the silkworm and other insect species.


Patient Autonomy and Quality of Care in Telehealthcare.
Telemedicine is a complex field including various applications and target groups. Especially telehealthcare is seen by many as a means to revolutionize medicine. It gives patients the opportunity to take charge of their own health by using self-tracking devices and allows health professionals to treat patients from a distance. To some, this means an empowerment of patient autonomy as well as an improvement in the quality of care. Others state the dangers of depersonalization of medicine and the pathologization of daily life. This paper examines the ethical implications of telehealthcare, focusing on patient autonomy and quality of care by analyzing metareviews, randomized controlled trials and narrative ethical analyses on the topic. As a result, we conclude that the technically enhanced encounter between patients and health professionals may mean an empowerment of patient autonomy when it goes along with a personal relationship based on trust, assistance and support. When it comes to the quality of care, telehealthcare may lead to an improvement as long it is adopted to the patient's individual needs.


Effects of metformin and Exenatide on insulin resistance and AMPKα-SIRT1 molecular pathway in PCOS rats.
This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10μg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.


Genetic toxicology of epichlorohydrin: a review.
Epichlorohydrin (ECH) is one of the more commercially important aliphatic epoxides used extensively as an industrial intermediate, a laboratory reagent, and as an insecticide. It is a volatile, colourless liquid with an ethereal odour. It behaves as an alkylating agent. Reports have shown it to cause the respiratory and dermal toxicity in animals and humans. It has also been reported to be carcinogenic in experimental models. Thus, the wide-spread use of this aliphatic epoxide is of great concern in human health problem. The purpose of this paper is to critically review and update the mutagenic and clastogenic effects of ECH based on available literature.


Purification of hydroxylamine oxidase from Thiosphaera pantotropha. Identification of electron acceptors that couple heterotrophic nitrification to aerobic denitrification.
Thiosphaera pantotropha, a Gram-negative heterotrophic nitrifying bacterium, expresses a soluble 20 kDa monomeric periplasmic hydroxylamine oxidase that differs markedly from the hydroxylamine oxidase found in autotrophic bacteria. This enzyme can use the periplasmic redox proteins, cytochrome c551 and pseudoazurin as electron acceptors, both of which can also donate electrons to denitrification enzymes. A model of electron transfer is proposed, that suggests a coupling of nitrification and provides a mechanism by which nitrification can play a role in dissipating reductant.


Acute transient macular detachment after uneventful cataract surgery in a highly myopic eye.
We report a case of a highly myopic patient who presented a serous macular detachment at 24 hours after uncomplicated cataract surgery. Surprisingly, after six days from surgery, a reabsorption of the detachment was noticed and the macular area returned to be anatomically normal without any surgical intervention. This early postoperative complication could be caused by changes in the vitreoretinal interface and ocular fluid dynamics or to a rupture of blood-retinal barriers due to postoperative inflammation. Our case reports on the occurrence of an early transient macular detachment after uneventful cataract surgery in a highly myopic eye. This finding suggests the importance of an OCT-based control in the immediate postoperative hours.


Postoperative medical treatment of lower urinary tract symptoms after benign prostatic hyperplasia surgery. Are we underestimating the problem?
The aim of this study was to determine whether well timed start of medical and surgical treatment of benign prostatic obstruction (BPO) influences the treatment's effectiveness and thus the patients' overall functional outcomes and quality of life. Pharmacological therapy even in high-volume (>80 cm3) BPH typically begins with α-blockers sole and only subsequently are 5ARI added. Several studies showed that acute urinary retention (AUR) developed more frequently in men who suffered severe lower urinary tract symptoms (LUTS) and who did not start combination therapy immediately. Moreover, there are no strict criteria which determine the right time for performing surgery in patients with mild and moderate LUTS, especially when pharmacological therapy fails. However, sometimes, the surgery does not eliminate all the symptoms, as it deals effectively with BPO, but does not treat an overactive bladder. Also, data show that surgery should be performed as soon as possible and be more radical after the first episode of AUR. A combination of α-blockers and 5ARI makes for a good starting point where the treatment of high volume BPH is concerned. Ideally, surgery should be performed immediately or as soon as possible in patients with the first episode of AUR and 'anatomic' BPH tissue removal is preferable (dissection of tissue along the prostate capsule to remove its maximum volume).


Injuries in youth soccer during the preseason.
To evaluate injuries occurring during the preseason in youth soccer players. Prospective cohort study over 1 preseason. 2009-2010 preseason. Subjects were 912 youths aged 12 to 19 years. The club's medical staff prospectively recorded all injuries. A reportable injury was defined as by the consensus statement on soccer injuries. Estimated injury rates per 1000 hours of exposure during the preseason period were calculated. Injury rates (injuries per 1000 hours of soccer exposure) during preseason practices by age group, as well as prevalence, severity, and type of injuries. Total incidence was 2.5 injuries per 1000 hours of exposure. Incidence of match and training injuries were 6.7 and 1.8 injuries per 1000 hours (P = 0.02), respectively. Injuries were sustained by 7.2% of players during the preseason, and 79% of the injuries involved the lower limbs, of which 23% were located to the thigh. Muscle strains and contusions were the most common injuries and external trauma the main cause. No age-related trend in the incidence of preseason injuries was found. During the preseason training period, athletic trainers should expect a majority of muscle strains, especially in the thigh region.