Effects of selective endothelin (ET)-A receptor antagonist versus dual ET-A/B receptor antagonist on hearts of streptozotocin-treated diabetic rats.
The aim was to study the differences in the effectiveness of two types of endothelin (ET) receptor antagonists (selective ET-A or dual ET-A/B antagonists) on the hearts of streptozotocin (STZ)-induced diabetic rats (type I diabetes) at functional and biochemical/molecular levels. Citrate saline (vehicle) or STZ was injected into rats. The ET-A/B dual receptor antagonist (SB209670, 1mg/kg/day) and the ET-A receptor antagonist (TA-0201, 1mg/kg/day) were then administered to these rats. One week after injection, the animals were separated into those receiving SB209670, TA-0201 or vehicle by 4-week osmotic mini-pump. The VEGF level and percent fractional shortening in the diabetic heart were significantly decreased compared to the non-diabetic heart, whereas SB209670 and TA-0201 treatments greatly and comparably prevented this decrease. SB209670 treatment was more effective in reversing decreased expressions of KDR and phosphorylated AKT, downstream of VEGF angiogenic signaling, than TA-0201 treatment. The eNOS levels in hearts were significantly higher in diabetic rats than in healthy rats, and this increase was significantly reduced by TA-0210 but not by SB209670 treatment. Improvement of KDR mRNA and pAKT levels by SB209670 but not TA-0201 suggests that dual ET-A/-B blockade may be effective in improving intracellular systems of these components in the diabetic rat heart. However, the present study also showed that TA-0201 or SB209670 improved percent fractional shortening and VEGF levels of the diabetic hearts to a similar extent, suggesting that ET-A blockade and dual ET-A/-B blockade are similarly effective in improving cardiac dysfunction in the diabetic rats.


Psychosomatic and Physical Well-Being Factors After Mind-Body Interventions in a Hospital Setting.
Mind-body interventions encompass a variety of treatments that directly affect health. Researchers have found that yoga can decrease symptoms of depression and anxiety as well as improve dietary patterns, enhance physical function and capacity, and enrich sleep. Research has shown that mindfulness can have psychological and physiological benefits and treat symptoms of anxiety and depression. This study intended to compare the benefits of 2 mind-body interventions-yoga and mindfulness-in a hospital setting. The research team performed a retrospective analysis of outcome data obtained from a hospital's programs. The study took place at a mind-body center at a hospital in Athens, GA (USA). Participants were 46 individuals enrolled either in a yoga (n = 24) or a mindfulness (n = 22) intervention program at the hospital. Participants self-selected a mind-body-intervention program offered at the hospital: yoga or mindfulness. They received guided training in their chosen intervention at weekly 2-h sessions for 6 to 9 wk. Participants completed measures of anxiety, depression, mindfulness, and quality of life at 2 points during the mind-body programs, at baseline and postintervention. The programs used the Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Freiburg-Mindfulness Inventory (FMI), Automatic Thought Questionnaire (ATQ), and RAND 36-Item Short Form Health Survey (SF-36). The results showed significant decreases between baseline and postintervention in depression (on BDI-II) and anxiety (on BAI) levels for participants in both groups; however, only participants in the mindfulness group showed significant increases in mindfulness (on FMI) and quality of life and decreases in the frequency of negative thoughts (on ATQ) and significant improvements in some health-related measures (on SF-36; all P < .05). However, a significant difference between the groups existed at postintervention only for limitations due to physical health on the SF-36. The overall findings suggest that both the programs are effective. Although significant differences existed between the groups only for limitations due to physical health, the significant increases in categories other than anxiety and depression for the mindfulness group suggest that mindfulness can offer a more encompassing intervention for improving psychosomatic well-being, although further research is needed.


Efficacy and safety of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.
We aimed to evaluate the efficacy and safety of anti-interleukin-1 therapeutics, including IL-1 antibodies, interleukin-1 receptor antagonists (IL-1 Ras) and IL-1 inhibitors, for knee osteoarthritis (KOA) treatment. Databases (Medline, Embase, Web of Science and CENTRAL) and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) of anti-interleukin-1 therapeutics from inception to August 31, 2022. The outcomes were the mean change in pain and function scores and the risk of adverse effects (AEs). In the 12 studies included, anti-interleukin-1 therapeutics were superior to placebo in terms of pain relief (standardized mean difference [SMD] = - 0.38, 95% confidence interval [CI] = - 1.82 to - 0.40, p < 0.001, I2 = 77%) and functional improvement (SMD = - 1.11, 95% CI = - 1.82 to - 0.40, p = 0.002, I2 = 96%). The incidence of any AE (risk ratio [RR] = 1.02, 95% CI = 0.88-1.18, p < 0.001, I2 = 76%) was higher following treatment with anti-interleukin-1 therapeutics than placebo, while no significant difference was found in the incidence of serious AEs (SAEs) or discontinuations due to AEs. Subgroup analyses showed that IL-1 antibodies and the IL-1 inhibitor provided pain relief (IL-1 antibodies: SMD = - 0.61, 95% CI = - 0.92 to - 0.31, p < 0.001; IL-1 inhibitor: SMD = - 0.39, 95% CI = - 0.72 to - 0.06, p = 0.02, I2 = 74.0%) and functional improvement (IL-1 antibodies: SMD = - 1.75, 95% CI = - 2.10 to - 1.40, p < 0.001; IL-1 inhibitor: SMD = - 0.28, 95% CI = - 0.83 to 0.27, p = 0.31, I2 = 88%) superior to those of placebo, whereas IL-1 Ras did not. However, the IL-1 inhibitor increased the incidence of any AE (RR = 1.35, 95% CI = 0.92-1.98, p < 0.001, I2 = 85%) but not the risk of SAEs or discontinuations due to AEs. IL-1 antibodies and IL-1 Ras showed no difference in safety compared with placebo. Anti-interleukin-1 therapeutics could relieve OA-related pain and improve function, but is probably associated with an increased risk of adverse events. Specially, IL-1 antibodies and an IL-1 inhibitor could relieve OA-related pain and improve function, whereas IL-1 Ras could not. IL-1 antibodies and IL-1 Ras were relatively safe options, but IL-1 inhibitors were associated with safety concerns.


Acute coronary syndromes in deployed military personnel.
The purpose of this study was to describe the cardiovascular (CV) risk profile of deployed military men who experience acute coronary syndrome (ACS). A retrospective record review of deployed military men who experienced ACS while deployed and were treated at an overseas military medical center between 2001 and 2007 was conducted to obtain the information for this descriptive study (N= 100). Acute myocardial infarction was diagnosed in 82% of the sample, and 18% experienced unstable angina. Subjects' mean age was 44.7 years (SD± 7.6; range 29-60) and most were enlisted and reservists. Risk factors included a family history of premature coronary artery disease (41%) and smoking (47%) as well as a history of hyperlipidemia (48%), hypertension (28%), and glucose abnormalities (6%). The group was overweight (BMI 27.77 kg/m(2) ± 3.2) and low risk for CV events (Framingham risk score 7.8%[± 4.4]). Young military men are regarded as the epitome of health and fitness; however, findings from this study suggest that this generally low-risk group do indeed have multiple CV risk factors and experience ACS. Early risk factor assessment and modification, including smoking cessation, weight management, and improving dyslipidemia, is essential.


Current use of fluid biomarkers as outcome measures in Multiple Sclerosis (MS): a review of ongoing pharmacological clinical trials.
The present study aims to describe the state of the art of fluid biomarkers use in ongoing multiple sclerosis (MS) clinical trials.A review of 608 ongoing protocols in the clinicaltrials.gov and EudraCT databases was performed. The trials enrolled patients with a diagnosis of relapsing remitting MS, secondary progressive MS, and/or primary progressive MS according to Revised McDonald criteria or relapsing MS according to Lublin et al. (2014). The presence of fluid biomarkers among the primary and/or secondary study outcomes was assessed.Overall, 5% of ongoing interventional studies on MS adopted fluid biomarkers. They were mostly used as secondary outcomes in phase 3-4 clinical trials to support the potential disease-modifying properties of the intervention. Most studies evaluated neurofilament light chains (NfLs). A small number considered other novel fluid biomarkers of neuroinflammation and neurodegeneration such as glial fibrillary acid protein (GFAP).Considering the numerous ongoing clinical trials in MS, still a small number adopted fluid biomarkers as outcome measures, thus testifying the distance from clinical practice. In most protocols, fluid biomarkers were used to evaluate the effectiveness of approved second-line therapies, but also, new drugs (particularly Bruton kinase inhibitors). NfLs were also adopted to monitor disease progression after natalizumab suspension in stable patients, cladribine efficacy after anti-CD20 discontinuation, and the efficacy of autologous hematopoietic stem cell transplant (AHSCT) compared to medical treatment. Nevertheless, further validation studies are needed for all considered fluid biomarkers to access clinical practice, and cost-effectiveness in the "real word" remains to be clarified.


HIV-1 molecular diversity in Brazil unveiled by 10 years of sampling by the national genotyping network.
HIV-1 has diversified into several subtypes and recombinant forms that are heterogeneously spread around the world. Understanding the distribution of viral variants and their temporal dynamics can help to design vaccines and monitor changes in viral transmission patterns. Brazil has one of the largest HIV-1 epidemics in the western-world and the molecular features of the virus circulating in the country are still not completely known. Over 50,000 partial HIV-1 genomes sampled between 2008 and 2017 by the Brazilian genotyping network (RENAGENO) were analyzed. Sequences were filtered by quality, duplicate sequences per patient were removed and subtyping was performed with online tools and molecular phylogeny. Association between patients' demographic data and subtypes were performed by calculating the relative risk in a multinomial analysis and trends in subtype prevalence were tested by Pearson correlation. HIV-1B was found to be the most prevalent subtype throughout the country except in the south, where HIV-1C prevails. An increasing trend in the proportion of HIV-1C and F1 was observed in several regions of the country, while HIV-1B tended to decrease. Men and highly educated individuals were more frequently infected by HIV-1B and non-B variants were more prevalent among women with lower education. Our results suggest that socio-demographic factors partially segregate HIV-1 diversity in Brazil while shaping viral transmission networks. Historical events could explain a preferential circulation of HIV-1B among men who have sex with men (MSM) and non-B variants among heterosexual individuals. In view of an increasing male/female ratio of AIDS cases in Brazil in the last 10-15 years, the decrease of HIV-1B prevalence is surprising and suggests a greater penetrance of non-B subtypes in MSM transmission chains.


On-line analysis of complex hydrocarbon mixtures using comprehensive two-dimensional gas chromatography.
This paper discusses the first setup for on-line qualitative and quantitative comprehensive two-dimensional gas chromatography (GC × GC) of complex hydrocarbon mixtures. A built-in 4-port 2-way valve allows switching between flame ionization detection (FID) and time-of-flight mass spectrometry (TOF-MS) between runs, without the need to cool down and vent the MS. Proper selection of GC carrier gas flow rates enables maximal agreement between the obtained chromatograms in both configurations. For on-line analysis of reactor effluents, a dedicated sampling system allows automatic sampling of the hot reactor effluent gases and immediate injection of the sample on the GC × GC. To determine a complete effluent composition in a single run of the GC × GC, a subzero oven starting temperature was employed. Modulation is started when the oven temperature reaches 40°C, thus dividing the chromatogram in a conventional 1D and a comprehensive 2D part. This work illustrates the mature and robust character of GC × GC, extending its capabilities from mere laboratory use to on-line routine analysis for industrial processes in the (petro-)chemical industry.


The effects of dopamine and D2 receptor antagonists on pituitary hormone secretion are intact in mice lacking dopamine D2L receptor.
The dopamine D2 receptor (D2) is involved in the regulation of pituitary hormone secretion. Two isoforms of the D2 receptor, termed D2L and D2S, have been identified. We previously generated D2L knockout mice (D2L-/-), which still express D2S. The present study examined the role of D2S and D2L in spontaneous and drug-induced pituitary hormone secretion. We found that D2L-/- mice had normal serum levels of prolactin and growth hormone. In addition, the antipsychotic drugs haloperidol and clozapine induced a similar dose-dependent increase in serum prolactin in both D2L-/- and wild-type mice. These results suggest that D2S can substitute for the function of D2L in the regulation of pituitary hormone secretion, and that the function of D2S is not dependent on the formation of a receptor heterodimer with D2L.


Association between childhood atopic dermatitis, malnutrition, and low bone mineral density: a US population-based study.
Children with atopic dermatitis (AD) have multiple risk factors for low bone mineral density (BMD). We analyzed data from 3049 children and adolescents aged 8-19 yrs from the 2005-2006 National Health and Nutrition Examination Survey, including a cross-sectional questionnaire, dual energy X-ray absorptiometry, and blood samples. In multivariate models that controlled for age, sex, race/ethnicity, level of education and household income, body mass index (BMI), and smoking in the household, AD was associated with lower BMD z-score for the total femur (survey linear regression; adjusted β [95% CI]: -0.42 [0.68, -0.16]), including trochanter (-0.29 [-0.54, -0.05]) and femoral neck (-0.29 [-0.53, -0.05]) and total lumbar spine (-0.31 [-0.52, -0.11]). Children with AD had higher median levels of serum IgE (110.0 vs. 53.0 kU/l), peripheral lymphocyte (2.9 vs. 2.5 × 10(3) cells/μl), and eosinophil counts (0.3 vs. 0.2 × 10(3) cells/μl) (Mann-Whitney U-test, p ≤ 0.003 for all), but not CRP levels (0.03 vs. 0.04 mg/dl) and higher odds of 25-OH vitamin D deficiency (survey logistic regression; odds ratio [OR] [95% CI]: 4.81 [1.21, 20.81]), low calcium (2.56 [1.24, 5.28]), low alkaline phosphatase (2.56 [1.20, 5.44]), and higher tertiles of LDH (tertile 2: 6.36 [1.75, 23.18]; tertile-3: 4.57 [1.32, 15.85]), but not parathyroid hormone (PTH) or albumin. Finally, children with AD had higher rates of low BMD, that is, BMD z-score <-2, of the femur (23.4% vs. 18.4%) and spine (35.3% vs. 24.5%). In multivariate logistic regression models of low BMD of femur and/or spine using stepwise selection of the 30 sociodemographic and clinical factors, laboratory values, and medications used, AD remained a significant covariate (1.33 [1.32-1.34]). The covariates with the largest effects on low BMD were low PTH and albumin, higher basophil count, Hispanic ethnicity, and BMI <5th percentile. Among children with AD, 56.2% of those with Hispanic origin, 52.8% with BMI <5th percentile, 75.0% with low albumin, and 54.0% with low PTH had low BMD. Children with AD have lower BMD, particularly those with malnutrition and Hispanic ethnicity.


Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort.
It is well established that chronic kidney disease (CKD) results in a significant burden on patients' health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60-75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Overall health care costs ranged from $26,889 (A1) to $42,139 (A3), and from $28,627 (G2) to $42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3]). Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers.


A high-resolution flux-matrix model describes the spread of diseases in a spatial network and the effect of mitigation strategies.
Propagation of an epidemic across a spatial network of communities is described by a variant of the SIR model accompanied by an intercommunity infectivity matrix. This matrix is estimated from fluxes between communities, obtained from cell-phone tracking data recorded in the USA between March 2020 and February 2021. We apply this model to the SARS-CoV-2 pandemic by fitting just one global parameter representing the frequency of interaction between individuals. We find that the predicted infections agree reasonably well with the reported cases. We clearly see the effect of "shelter-in-place" policies introduced at the onset of the pandemic. Interestingly, a model with uniform transmission rates produces similar results, suggesting that the epidemic transmission was deeply influenced by air travel. We then study the effect of alternative mitigation policies, in particular restricting long-range travel. We find that this policy is successful in decreasing the epidemic size and slowing down the spread, but less effective than the shelter-in-place policy. This policy can result in a pulled wave of infections. We express its velocity and characterize the shape of the traveling front as a function of the epidemiological parameters. Finally, we discuss a policy of selectively constraining travel based on an edge-betweenness criterion.


Diagnosis of abdominal aortic hypoplasia by state-of-the-art MR angiography.
Abdominal aortic hypoplasia is a rare vascular variant with possible major clinical sequelae when the renal arteries are also involved. The condition is thought to result from embryonic overfusion of the two dorsal aortas. The diagnosis may be considered in patients presenting with hypertension in the neonatal period and severely reduced or absent arterial pulses in the groin. We present contrast-enhanced state-of-the-art magnetic resonance angiography imaging findings in an 8-year-old boy with abdominal aortic hypoplasia.


Estimation of Ischemia Modified Albumin (IMA) Levels in Patients with Acute Coronary Syndrome.
Myocardial ischemia produces free radicals that catalyze a series of oxidative reactions that damage healthy tissues. The N-terminal sequence of albumin is one of the proteins modified by these highly reactive oxygen species and forms the ischemia modified albumin (IMA). This study involves investigations undertaken in different study groups to assess the levels of IMA. Mean serum IMA levels (U/mL) in patients with ST-segment elevated myocardial infarction (92.1 ± 10.6), non-ST-segment elevated myocardial infarction (87.3 ± 5.95) and unstable angina (UA) (88.9 ± 6.16) were significantly higher than non-cardiac chest pain (77.9 ± 6.69) and also healthy subjects (54.7 ± 17.2) (p < 0.001). IMA is a highly sensitive marker and has a high predictive value, which might prove the usefulness of this biomarker for early detection of myocardial ischemia. These data indicate a possible role of the IMA test in the early triage of patients with chest pain.


Corrigendum to "Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and COVID-19 infection during pregnancy" [Trav Med Infect Dis. (2020) 101641].
[This corrects the article DOI: 10.1016/j.tmaid.2020.101641.].


Preemptive analgesia: no relevant advantage of preoperative compared with postoperative intravenous administration of morphine, ketamine, and clonidine in patients undergoing transperitoneal tumor nephrectomy.
Preemptive analgesia often failed in the clinical arena because application of a single intravenously applied drug may not prevent nociceptive input and spinal pain processing sufficiently. We therefore used an intravenous (IV), multireceptor approach and tested the preemptive analgesic effect of the antinociceptive drugs morphine, ketamine, and clonidine given before or immediately after surgery. A double-blind, randomized, prospective study was performed in 30 patients undergoing transperitoneal tumor nephrectomy (via median laparotomy). Standard general anesthesia procedure without opioids was used. After induction, patients were randomly allocated to receive 150 microg x kg(-1) of morphine, 150 microg x kg(-1) of ketamine, and 5 microg x kg(-1) of clonidine intravenously via a motor-driven pump within 15 minutes, either before or immediately after surgery. Patient-controlled analgesia (PCA) with the opioid piritramide (IV) was used for postoperative analgesia. Postoperative pain at rest and during induced cough was quantified by analgesic requirement and pain scores (visual analog scale [VAS]) within 48 hours. There was no significant difference in analgesic requirement of piritramide and pain scores at rest or during induced cough. In contrast to encouraging observations on the combination of antinociceptive drugs, the multireceptor approach tested here failed to exert a clinically relevant effect.


Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1α in schizophrenia.
The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such molecule is neurexin 1α (NRXN1α), a presynaptic cell adhesion molecule. In addition, novel autoantibodies that target the nervous system have been found in patients with encephalitis and neurological disorders. Some of these autoantibodies inhibit synaptic antigen molecules. Studies have examined the association between schizophrenia and autoimmunity; however, the pathological data remain unclear. Here, we identified a novel autoantibody against NRXN1α in patients with schizophrenia (n = 2.1%) in a Japanese cohort (n = 387). None of the healthy control participants (n = 362) were positive for anti-NRXN1α autoantibodies. Anti-NRXN1α autoantibodies isolated from patients with schizophrenia inhibited the molecular interaction between NRXN1α and Neuroligin 1 (NLGN1) and between NRXN1α and Neuroligin 2 (NLGN2). Additionally, these autoantibodies reduced the frequency of the miniature excitatory postsynaptic current in the frontal cortex of mice. Administration of anti-NRXN1α autoantibodies from patients with schizophrenia into the cerebrospinal fluid of mice reduced the number of spines/synapses in the frontal cortex and induced schizophrenia-related behaviors such as reduced cognition, impaired pre-pulse inhibition, and reduced social novelty preference. These changes were improved through the removal of anti-NRXN1α autoantibodies from the IgG fraction of patients with schizophrenia. These findings demonstrate that anti-NRXN1α autoantibodies transferred from patients with schizophrenia cause schizophrenia-related pathology in mice. Removal of anti-NRXN1α autoantibodies may be a therapeutic target for a subgroup of patients who are positive for these autoantibodies.


Assessment of the complementary and integrative medicine utilization among patients with multiple sclerosis using a translated and adapted version of the international questionnaire (I-CAM-QP): A cross-sectional study in Southern Iran.
To assess the prevalence of and factors related to complementary and integrative medicine (CIM) use among multiple sclerosis (MS) patients, using a translated and adapted version of a standard international questionnaire. International complementary and alternative medicine questionnaire (I-CAM-Q) was used. A cross-sectional study was done to assess the prevalence of and factors associated with CIM use among MS patients in Southern Iran. Patients who were randomly selected from MS registry center, were interviewed via phone calls. Three hundred patients were enrolled in the study; 69% of them were female. Their mean age was 36.6±8.53 years and the mean duration of the disease was 5.6 ± 4.22 years. In all, 99.3% (95% CI) of the patients had used at least one type of CIM. Herbal medicines and dietary supplements were the most commonly used CIM type (97.3%; 95% CI). Praying was the most common modality among all CIM subgroups (81.3%; 95% CI). Long term illness (MS) was selected as the main reason for the last use of all CIM types. Having non-tertiary education and having sequel due to MS were related to visiting a CIM provider (adjusted odds ratio (AOR) = 2.32, 95% confidence interval (CI) = 1.22-4.43), (AOR = 2.67, 95% CI = 1.47-4.83) respectively. Being female was related to the use of self-help practices (AOR = 3.41, 95% CI = 1.5-7.72). There is a high prevalence of CIM use among MS patients. Therefore, patient- physician communication about CIM use should be emphasized.


Comparison of mobile phone usage and physical activity on glycemic status, body composition & lifestyle in male Saudi mobile phone users.
&Objectives: This study aimed to compare the effects of mobile phone usage and physical activity on HbA1c, body composition, and lifestyle among male Saudi Arabian mobile phone users. The study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia from July 2020 to July 2021. The study sample consisted of 203 non-smoker male Saudi participants aged from 20 to 60 years who used mobile phones. Personal information was obtained through interviews using a proforma. The participants were divided into three groups according to their daily mobile phone usage: Group (1): less than 2 h, Group (2): 2-3 h, and Group (3): more than 3 h, and according to their physical activities: Group (1): sedentary, Group (2): average, and Group (3): athletes. Glycated Hemoglobin (HbA1c), Bioelectrical Impedance Analysis (BIA), and (SF) 36- items survey was performed. The mean age of 203 Saudi male adult participants was 28.0 ± 10.4 years. Mobile phone usage in the less than 2 h group was (33.5%), between 2-3 h (22.7%), and more than 3 h (43.8%) respectively. The mean age of Group (3), who used mobile phones for more than 3 h, was the lowest (23.9 ± 5.7). The results showed that HbA1C levels were almost equal in all three groups (5.8 ± 0.4, 5.7 ± 0.4, and 5.7 ± 0.3 respectively). In addition, emotional well-being and social functioning showed insignificant decreases in the more than 3 h group compared to other groups of mobile phone usage (69.3 ± 15.7, 70.9 ± 15.5, 65.2 ± 16.0, p = .091 and 82.9 ± 201, 81.2 ± 18.7, 77.6 ± 21.6, p = .267) respectively. No effect was detected between groups regarding various body compositions. Regarding physical activity classifications: the sedentary group constituted (36%) of the sample, whereas the average and athlete groups represented (53.7%) and (10.3%) of the total sample respectively. There was a significant decrease in BMI (29.6 ± 7.8, 25.3 ± 5.1,24.7 ± 5.6, p = .000), fat mass (24.7 ± 15.0, 17.1 ± 9.1, 15.3 ± 10.6, p = .000), and free fat mass (64.0 ± 10.2, 56.8 ± 8.7, 57.5 ± 8.0, p = .000) in the average and the athletic groups compared to the sedentary group. No significant difference was found in HbA1c between physical activity groups (5.8 ± 0.4, 5.7 ± 0.4, 5.7 ± 0.4, p = .218). Mobile phone usage does not affect HbA1c and body composition parameters. Furthermore, we found the youngers used mobile phones longer than others. Insignificant decrease in emotional well-being and social functioning parameters of the style of life due to long mobile phone usage which needs more attention.


Coiled-coil protein composition of 22 proteomes--differences and common themes in subcellular infrastructure and traffic control.
Long alpha-helical coiled-coil proteins are involved in diverse organizational and regulatory processes in eukaryotic cells. They provide cables and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize membrane systems and tissues, motors, levers, rotating arms, and possibly springs. Mutations in long coiled-coil proteins have been implemented in a growing number of human diseases. Using the coiled-coil prediction program MultiCoil, we have previously identified all long coiled-coil proteins from the model plant Arabidopsis thaliana and have established a searchable Arabidopsis coiled-coil protein database. Here, we have identified all proteins with long coiled-coil domains from 21 additional fully sequenced genomes. Because regions predicted to form coiled-coils interfere with sequence homology determination, we have developed a sequence comparison and clustering strategy based on masking predicted coiled-coil domains. Comparing and grouping all long coiled-coil proteins from 22 genomes, the kingdom-specificity of coiled-coil protein families was determined. At the same time, a number of proteins with unknown function could be grouped with already characterized proteins from other organisms. MultiCoil predicts proteins with extended coiled-coil domains (more than 250 amino acids) to be largely absent from bacterial genomes, but present in archaea and eukaryotes. The structural maintenance of chromosomes proteins and their relatives are the only long coiled-coil protein family clearly conserved throughout all kingdoms, indicating their ancient nature. Motor proteins, membrane tethering and vesicle transport proteins are the dominant eukaryote-specific long coiled-coil proteins, suggesting that coiled-coil proteins have gained functions in the increasingly complex processes of subcellular infrastructure maintenance and trafficking control of the eukaryotic cell.


Introduction of an early pregnancy assessment unit: audit on the first 6 months of service.
Women experiencing bleeding in early pregnancy suffer considerable anxiety. Waiting for a considerable time for a diagnosis adds to their grievance. Early Pregnancy Assessment Unit (EPAU) is a dedicated service that provides quick and easy accessibility to diagnosis, treatment and support service. To monitor the first 6 months of the EPAU service in the Rotunda Hospital, to identify its shortcomings, so that we can ensure effective EPAU care in future. A retrospective audit between July and December 2002 was performed. A majority of patients (83.4%) were self-referrals. All patients were seen between 1 and 3 h. In the miscarriage group, 218/278 (78.4%) was managed surgically by evacuation and a further 60/278 (21.6%) received conservative or medical treatment. Among 13 ectopic pregnancies, 5/13 (39%) had laparoscopic management. This clinic has enabled us to manage early pregnancy bleeding in an effective manner within a satisfactory time period. The high surgical intervention rate for miscarriages is highlighted to support the need for greater emphasis on medical and expectant management.


Cationic doping induced sulfur vacancy formation in polyionic sulfide for enhanced electromagnetic wave absorption.
Vacancy engineering has been shown to be an effective way to tune the electromagnetic parameters of electromagnetic wave (EMW) absorbers and improve their absorption properties. However, the current methods to induce the formation of sulfur vacancies are not enough, and the contribution of sulfur vacancies to EMW absorption has not been clearly described. This work proposes a method to induce sulfur vacancies generation in the Cu2ZnSnS4 (CZTS) system by cation doping. It is found that the formation of sulfur vacancies depends on reactivity with doping cations and the less reactive cation is more favorable for the formation of sulfur vacancies. Benefiting from the improved sulfur vacancies concentration, the defect-induced polarization and dipole polarization are greatly enhanced, which allows the EMW absorber to exhibit excellent EMW absorption performance. Therefore, the minimum reflection loss of the cation-doped CZTS reaches -61.80 dB at a thickness of 2.00 mm, and the effective absorption bandwidth reaches 6.29 GHz at 2.30 mm. This work not only expounds on the significant roles of sulfur vacancies in EMW absorption mechanism, but also presents a novel idea for defect construction of copper-based chalcogenide semiconductor materials.


The effect of phosphodiesterase-5 inhibition by sildenafil citrate on inflammation and apoptosis in rat experimental colitis.
To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant-antioxidant status and apoptosis in rats with colitis. Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30 mg/ml; 0.8 ml) given intrarectally to Sprague-Dawley rats. Sildenafil (25 mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7 days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25 mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25 mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays. The macroscopic lesion score of the colitis group was reduced by SIL (p < 0.01) and this effect was abolished by l-NAME (p < 0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p < 0.01 and p < 0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p < 0.001). Sildenafil also reduced the elevated MPO of the colitis group (p < 0.001) and this effect was reversed by L-NAME (p < 0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p < 0.001 and p < 0.01, respectively). Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant-antioxidant status, prevention of apoptosis, superoxide production and cytokine release.


Cardiothoracic imaging findings of Proteus syndrome.
In this work, we sought to delineate the prevalence of cardiothoracic imaging findings of Proteus syndrome in a large cohort at our institution. Of 53 individuals with a confirmed diagnosis of Proteus syndrome at our institution from 10/2001 to 10/2019, 38 individuals (men, n = 23; average age = 24 years) underwent cardiothoracic imaging (routine chest CT, CT pulmonary angiography and/or cardiac MRI). All studies were retrospectively and independently reviewed by two fellowship-trained cardiothoracic readers. Disagreements were resolved by consensus. Differences between variables were analyzed via parametric and nonparametric tests based on the normality of the distribution. The cardiothoracic findings of Proteus syndrome were diverse, but several were much more common and included: scoliosis from bony overgrowth (94%), pulmonary venous dilation (62%), band-like areas of lung scarring (56%), and hyperlucent lung parenchyma (50%). In addition, of 20 individuals who underwent cardiac MRI, 9/20 (45%) had intramyocardial fat, mostly involving the endocardial surface of the left ventricular septal wall. There was no statistically significant difference among the functional cardiac parameters between individuals with and without intramyocardial fat. Only one individual with intramyocardial fat had mildly decreased function (LVEF = 53%), while all others had normal ejection fraction.


Physicians' views on how specialty-specific the first year of residency should be.
The nature of the first year of postgraduate medical education has gone through many changes over the years. Relatively recent changes have made this first year into a specialty-specific experience. Medical students are increasingly experiencing a narrowed and less broad-based clinical education. Many students, residents, and attending physicians complain that they wish they had had a "rotating" or "flexible" internship. Graduate medical education authorities have recently recommended that the internship year return to a broad-based general medical education experience. In 1989, the authors surveyed the entire physician faculty and housestaff at a large academic health sciences center, asking them what type of first postgraduate year (PGY-1) the physicians had experienced themselves and what type of PGY-1 they recommended for future graduating medical students. Over one-third strongly recommended that the PGY-1 should be broad-based and not specialty-specific.


Circulating immune complexes and rheumatoid factors in patients with farmer's lung.
Circulating IgG immune complexes (CICs), IgM rheumatoid factors (RFs), complement level (C3 and C4), and IgG antibodies to Aspergillus fumigatus, Aspergillus umbrosus, Thermoactinomyces vulgaris, and Micropolyspora faeni were analysed in the sera of 14 patients with farmer's lung (FL), 10 in the acute and four in the subacute phase of the disease. Ten spouses of FL patients served as exposed healthy controls. C3 and C4 were measured fluoronephelometrically. C3 levels were above the normal range and C4 levels near the upper limit of the normal range in both patients and controls; no statistically significant difference between patients and controls were observed. CICs were determined by enzyme immunoassays (EIA) of conglutinin-binding (KgB) and Clq-binding (ClqB). CIC levels above the normal range were detected in 12 (KgB-EIA) and nine (ClqB-EIA) of the patients and three (KgB-EIA) and six (ClqB-EIA) of the controls. No statistically significant differences were found in the mean levels between patients and controls. In contrast, RF levels in the acute phase of FL were significantly higher in the patients (P less than 0.01) than in the controls. CICs correlated positively with most microbial IgG antibodies, but negatively with RFs. RFs also correlated negatively with microbial IgG antibodies, as well as with both C3 and C4. In FL, the increased RF level may, in the absence of increased CIC and decreased complement levels, represent an immune response (IgM anti-IgG autoantibodies) induced by local mechanisms of IgG immune complexes in the lungs.


Inter-alpha-trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk, activity, and treatment outcomes of rheumatoid arthritis.
Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA. After the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme-linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17A at baseline of RA patients were also detected by ELISA. ITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2-213.5) ng/mL) than in HCs (306.8 (IQR: 238.9-435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C-reactive protein (CRP) (rs = -0.358, p < 0.001) and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) (rs = -0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF-α (rs = -0.337, p = 0.001), IL-6 (rs = -0.221, p = 0.033), and IL-17A (rs = -0.368, p < 0.001) in RA patients, but not correlated with IL-1β (rs = -0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05). Circulating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.


Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B.
HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared with HIV-1B. The impact of HIV-1C Tat on the chemotaxis of the main lymphocyte subpopulations in the cerebrospinal fluid (CSF) and the peripheral blood (PB) is unclear. We hypothesized that there would be a lower frequency of specific lymphocyte subpopulations CD3+ or CD19+ in CSF in HIV-1C than in HIV-1B. The objectives were to detect the differences in the proportions of main lymphocyte subpopulations in CSF and PB, between people with HIV (PWH) and HIV-1-uninfected volunteers (PWoH) and in HIV-1B and HIV-1C. Lymphocyte immunophenotyping was studied in CSF and paired PB samples of PWH (n = 22) and PWoH (n = 14). Lymphocytes were analyzed within the CD45+ gated region. The proportions of CSF CD3+CD4+, CD3+CD8+, and CD3-CD19+ lymphocytes in CSF were comparable in HIV-1B and C. There was an increase in the proportion of CD3+CD8+ cells and a decrease in CD3+CD4+ T cells (ps = 0.016) in the CSF samples of the PWH compared with the PWoH group. In the PWH group, both CD3+CD4+ and CD3+CD8+ lymphocytes were significantly higher in the CSF than in the PB (p = 0.047 and 0.005). The proportion of CD3+CD4+ was lower and that of CD3+CD8+ was higher in the CSF samples of the aviremic group than that of HIV-negative control (p = 0.0008 and < 0.0001, respectively). HIV-1C Tat substitution (C30S) did not interfere with the CNS migration of the main lymphocyte subpopulations. This is the first study to evaluate these lymphocytes in CSF and PB of HIV-1C compared with HIV-1B.


The trigeminal retrograde transfer pathway in the treatment of neurodegeneration.
The trigeminal sensory system was evaluated for the retrograde transfer of gene therapy vectors into the CNS. The feline immunodeficiency viral vector, FIV(HEXB), encoding for the human HEXB gene, was injected intra-articularly in the temporomandibular joint of 12 week-old HexB(-/-) mice displaying clinical and histopathological signs of Sandhoff disease. This treatment regiment reduced GM(2) storage and ameliorated neuroinflammation in the brain of HexB(-/-) mice, as well as attenuated behavioral deficits. In conclusion, retrograde transfer along trigeminal sensory nerves may prove to be a valuable route of gene therapy administration for the treatment of lysosomal storage disorders and other neurodegenerative diseases.


Specific lipid recognition is a general feature of CD300 and TREM molecules.
CD300, triggering receptor expressed on myeloid cells (TREM), and TREM-like (TREML) receptors are important regulators of the mammalian immune response. Homologs of these receptors, which occur in activating and inhibitory transmembrane forms as well as soluble variants, are found throughout the jawed vertebrates. Specific ligands for most members of these receptor families remain elusive. We report here that at least 11 separate receptors from the CD300, TREM, and TREML families engage in robust and specific interactions with major polar lipids found in prokaryotic and eukaryotic cell membranes. Both soluble and membrane-bound receptor forms exhibit lipid interactions in the solid phase as well as in a physiological signaling context. Overlapping but distinctive patterns of receptor specificity suggest that the CD300/TREM system as a whole may discriminate immunological stimuli based on lipid signatures, thereby influencing downstream responses.


Changes in drug sensitivity following acute and chronic exercise.
A number of factors are known to influence drug sensitivity. These include biological variables such as genetics, age, endocrine status and gender, as well as environmental variables such as operant schedules, ambient temperature and sleep deprivation. Additional factors function as either biological or environmental variables in different situations. For example, chronic drug administration can produce tolerance and cross tolerance and function as a biological variable. Acute administration of the same compound can function as an environmental variable. The present study examined exercise as both a biological and an environmental variable influencing drug sensitivity. Chronic exercise leads to relatively long term changes in physical fitness level, and functions as a biological variable. Fitness level did not influence drug sensitivity when physically conditioned animals and non-exercised control subjects were compared under rested conditions. Mild acute exercise, an environmental variable, increased sensitivity to muscarinic antagonists in the control subjects but not in the exercise trained animals. These results indicate that exercise state should be considered as an environmental variable capable of influencing drug response and that biological fitness level modifies this effect.


Nondestructive determination of compound amoxicillin powder by NIR spectroscopy with the aid of chemometrics.
Near-infrared (NIR) spectroscopy, in combination with chemometrics, enables nondestructive analysis of solid samples without time-consuming sample preparation methods. A new method for the nondestructive determination of compound amoxicillin powder drug via NIR spectroscopy combined with an improved neural network model based on principal component analysis (PCA) and radial basis function (RBF) neural networks is investigated. The PCA technique is applied to extraction relevant features from lots of spectra data in order to reduce the input variables of the RBF neural networks. Various optimum principal component analysis--radial basis function (PCA-RBF) network models based on conventional spectra and preprocessing spectra (standard normal variate (SNV) and multiplicative scatter correction (MSC)) have been established and compared. Principal component regression (PCR) and partial least squares (PLS) multivariate calibrations are also used, which are compared with PCA-RBF neural networks. Experiment results show that the proposed PCA-RBF method is more efficient than PCR and PLS multivariate calibrations. And the PCA-RBF approach with SNV preprocessing spectra is found to provide the best performance.


Guidelines of the French society of endocrinology for the management of thyroid nodules.
The present document is a follow-up of the clinical practice guidelines of the French Society of Endocrinology, which were established for the use of its members and made available to scientific communities and physicians. Based on a critical analysis of data from the literature, consensuses and guidelines that have already been published internationally, it constitutes an update of the report on the diagnostic management of thyroid nodules that was proposed in France, in 1995, under the auspices of the French National Agency for Medical Evaluation (l'Agence nationale d'évaluation médicale). The current guidelines were deliberated beforehand by a number of physicians that are recognised for their expertise on the subject, coming from the specialities of endocrinology (the French Thyroid Research Group) and surgery (the French Association for Endocrine Surgery), as well as representatives from the fields of biology, ultrasonography, cytology and nuclear medicine. The guidelines were presented and submitted for the opinion of the members of the Society at its annual conference, which was held in Nice from 7-10 October 2009. The amended document was posted on the website of the Society and benefited from additional remarks of its members. The final version that is presented here was not subjected to methodological validation. It does not claim to be universal in its scope and will need to be revised in concert with progress made in technical and developmental concepts. It constitutes a document that the Society deems useful for distribution concerning the management of thyroid nodules, which is current, efficient and cost effective.


Effects of Shoe-Stiffening Inserts on Lower Extremity Kinematics in Individuals With First Metatarsophalangeal Joint Osteoarthritis.
To examine the effects of shoe-stiffening inserts on lower extremity kinematics in individuals with first metatarsophalangeal (MTP) joint osteoarthritis (OA). Forty-eight individuals with radiographically confirmed first MTP joint OA (24 male and 24 female; mean ± SD age 57.8 ± 10.5 years) were randomized to receive either shoe-stiffening inserts or sham inserts and underwent gait analysis during level walking using a 10-camera infrared Vicon motion analysis system. Sagittal plane kinematics of the first MTP, ankle, knee, and hip joints were compared between the shoe only (control) and insert conditions in both groups (within-groups) and between both insert conditions (between-groups). Compared to the shoe only condition, the sham insert reduced knee flexion and total excursion, and the shoe-stiffening insert reduced first MTP joint maximum dorsiflexion and ankle joint maximum plantarflexion, and increased maximum knee flexion and total excursion. Between-group comparisons indicated that the shoe-stiffening inserts significantly decreased first MTP joint maximum dorsiflexion, ankle joint maximum plantarflexion, and total excursion and increased knee joint maximum flexion and total excursion compared to the sham inserts. Carbon fiber shoe-stiffening inserts significantly alter sagittal plane lower extremity joint kinematics during walking, particularly first MTP joint maximum dorsiflexion. These findings provide insights into the mechanisms that may be responsible for their clinical effectiveness in the treatment of first MTP joint OA and potentially explain changes in symptoms in other lower extremity joints.


Pupillometry study of brimonidine tartrate 0.2% and apraclonidine 0.5%.
This study investigated possible effects of brimonidine tartrate 0.2% and apraclonidine 0.5% on pupil diameter. Ten subjects between 20 and 40 years of age participated. A Colvard pupillometer (Oasis Medical) was used to measure pupil diameter. Baseline and serial measurements were obtained at 3 luminance levels (>6.4, <0.82-0.4, and <0.2-0.02 cd/m(2)) during a 4-hour interval following instillation of 1 drop of brimonidine tartrate 0.2% or apraclonidine 0.5% in one eye versus a placebo in the contralateral eye. The measurements for each drug were obtained on different days. A nested random effects model controlling for subject's age, race, and sex was used for statistical analysis. A maximum reduction in pupil diameter was observed at 90 minutes from instillation (1.40 mm at >6.4 cd/m(2), 1.69 mm at <0.82-0.4 cd/m(2), and 1.55 mm at <0.2-0.02 cd/m(2)) for brimonidine tartrate 0.2%. At all time intervals and illumination levels, miosis (P < .01) occurred. Apraclonidine 0.5% did not produce a significant effect on pupil diameter. Brimonidine tartrate 0.2% produced a moderate miotic effect. No effect was observed for apraclonidine 0.5%. A predominant agonistic effect on α-2 receptors of the iris dilator may explain this behavior.


Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance.
The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis. Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population. Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay. Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance. The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.


The Cardiac Risk Factors of Coronary Artery Disease and its relationship with Cardiopulmonary resuscitation: A retrospective study.
Cardiovascular diseases are considered as the most prevalent serious disease in developed countries, and act as the number one cause of death among men and women in all ages and from all races. The present research aims at determining the relationship between risk factors of cardiovascular diseases and consequences of cardiopulmonary resuscitation (CPR). The present study is a retrospective analytic-cross sectional research performed on 100 patients in need for CPR (successful and unsuccessful) during March 2017 - June 2017. As research instrument, a pre-designed checklist was used including demographic information, clinical and medical information, and the information related to modifiable and non-modifiable risk factors of cardiovascular diseases. Obtained results indicated that, 57.1% of the successful CPR cases were administered on men, while 55.1% of unsuccessful CPR cases were administered on women. The patients diagnosed with myocardial infarction were in further need for CPR (rate of successful CPR: 66.7%, and rate of unsuccessful CPR: 61.9%). Significant associations were found between CPR duration, post-CPR survival time (survival time after CPR), systolic blood pressure, diastolic blood pressure, triglyceride level, diabetes, fasting blood sugar level, and body mass index, in one hand, and type of CPR, on the other hand (p < 0.05). Results of the present research showed that, there is a significant relationship between modifiable risk factors of cardiovascular diseases and consequences of CPR.


The Mother-Child Relationship during the First Months of Life: Preliminary Considerations in Preterm as Compared with Term Mother-Infant Dyads.
From the prognostic perspective, the quality of the mother-child relationship during the first months of life has been variously associated with different factors such as the child's psychomotor/cognitive development and emotional-behavioral disorders. The main aim of this study was to describe, at term age and 3 months of corrected age, the features and the prevalent patterns of the mother-child relationship in a group of 20 mother-preterm infant dyads and to compare them with those of a group of 20 mother-term infant dyads. A relatively high rate of inadequate dyadic synchrony was found in our sample of preterms at 40 weeks of gestational age (half of the sample analyzed). The quality of the dyadic relationship and the prevalent patterns of the mother-child relationship were found to differ between the two groups we studied; moreover, the subjects at risk of relational problems remained substantially the same during the first 3 months of life. These data underline that in preterm children, the first weeks of life, coinciding with their hospitalization, represent a crucial time for establishing a valid dyadic relationship and for considering and planning any preventive interventions; after all, the earlier the risk of relational problems becomes a real possibility, the more likely it is to negatively impact on a child's overall development.


Vibration stimulation during non-fatiguing tonic contraction induces outlasting neuroplastic effects.
The objective was to explore if vibration superposed to tonic contraction induces plastic changes in the contra- and ipsilateral motor cortex. Healthy subjects (n=12) abducted the right index finger with a force 5% of maximal voluntary contraction (MVC) against the lever of a torque motor while a 60 Hz vibration stimulus of 10 min was delivered. Motor evoked potentials (MEPs) after single and paired-pulse transcranial magnetic stimulation (TMS) were recorded from the first dorsal interosseous muscle of right and left hand pre, during, post and 30 min post-stimulation. The TMS assessments were employed with tonic contraction alone (TONIC) and with superposed vibrostimulation (VIBRO), each for the ipsi- and contralateral cortex separately. In the contralateral cortex: resting motor threshold (rMT) decreased, MEP amplitudes increased, short-interval intracortical inhibition (SICI) reduced and intracortical facilitation (ICF) increased post VIBRO, while no changes occurred post TONIC. In the ipsilateral cortex: rMT decreased, MEP amplitude increased and SICI reduced during TONIC, while no changes occurred post TONIC, during and post VIBRO. Vibration superposed to tonic contraction, induces lasting (30 min) plastic changes, whereas contraction alone caused no outlasting effects. Mainly intrinsic intracortical mechanisms are involved because spinal adaptation could be excluded (F-wave assessments). These findings have a therapeutic potential in the functional recovery of motor deficits with robot-aided devices.


Acute ankle sprain: is there a best support?
Acute lateral ankle sprain accounts for 85% of all sprains, being generally accepted as the most common sports-related ligamentous injury. There is a lack of consensus about the optimal management of these injuries despite their frequency. The time-honoured mantra of rest, ice, elevation and compression is still commonly used, even though the current evidence for compression is conflicting. A prospective randomized controlled clinical trial was carried out in the emergency department of a regional hospital in Ireland to compare outcomes, in terms of ankle function, pain improvement and return-to-work times, in adults presenting within 24 h of first-time acute lateral ankle sprain, among three external supports. We found no statistically significant differences among all three treatments in terms of ankle joint function, using the Karlsson ankle function scale, at 10 or 30-days follow-up. There was a tendency for Elastoplast bandaging to provide better average ankle function at both time points, when compared with double tubigrip and no support. Participants returned to work an average 2 days earlier, if treated with Elastoplast. This study found no statistically significant difference in ankle function between double tubigrip bandage, Elastoplast bandage and no support at 10 or 30-days follow-up.


Phosphatidylinositol synthase from yeast.
PI is an important precursor for polyphosphoinositides and some sphingolipids and is also involved in the glycolipid anchoring of plasma membrane proteins. This lipid is synthesized from CDP-diacylglycerol and myo-inositol by PI synthase, an enzyme localized in the outer mitochondrial membranes and microsomes in yeast. PI synthase was highly purified from yeast microsomes after solubilization with Triton X-100. The activity is dependent on Mn2+ or Mg2+ and Triton X-100. The reaction follows a sequential Bi-Bi mechanism with binding to CDP-diacylglycerol before myo-inositol and releasing PI prior to CMP. Unlike most of the yeast phospholipid-synthesizing enzymes, PI synthase is a constitutive enzyme. Its expression is insensitive to the addition of myo-inositol and choline to culture medium or the transition of growth phase. The primary translate deduced from the encoding gene, PIS, comprises 220 amino acid residues with a calculated molecular mass of 23,613. The sequence contains several hydrophobic regions and resembles that of the human enzyme. The sequence also contains the local, conserved region found in enzymes catalyzing the transfer of the phosphoalcohol moiety from CDP-alcohol, such as phosphatidylserine synthase, cholinephosphotransferase and phosphatidylglycerolphosphate synthase. Substitution of amino acid at position 114 from His (CAC) to Gln (CAA) results in a 200-fold increase in Km of the enzyme for myo-inositol, making cells auxotrophic for myo-inositol. Disruption of the PIS locus in the genome is lethal, indicating that PI is essential for the survival and growth of yeast cells.


Carbon monoxide-promoted carbene insertion into the aryl substituent of an N-heterocyclic carbene ligand: Buchner reaction in a ruthenium carbene complex.
In the presence of carbon monoxide, ruthenium carbenes give a net insertion/ring expansion (Buchner reaction) into one of the aromatic rings of the N-heterocyclic carbene ligand. In alkene metathesis applications, the N-heterocyclic carbene ligand is both robust and typically inert to reactions with the metal-bound carbene. This unique reaction is completely regioselective. The complexes obtained through ring expansion were fully characterized in the solid state using X-ray crystallography and in solution using NMR and IR spectroscopy.


Singlet oxygen production by photosystem II is caused by misses of the oxygen evolving complex.
Singlet oxygen (1 O2 ) is a harmful species that functions also as a signaling molecule. In chloroplasts, 1 O2 is produced via charge recombination reactions in photosystem II, but which recombination pathway(s) produce triplet Chl and 1 O2 remains open. Furthermore, the role of 1 O2 in photoinhibition is not clear. We compared temperature dependences of 1 O2 production, photoinhibition, and recombination pathways. 1 O2 production by pumpkin thylakoids increased from -2 to +35°C, ruling out recombination of the primary charge pair as a main contributor. S2 QA - or S2 QB - recombination pathways, in turn, had too steep temperature dependences. Instead, the temperature dependence of 1 O2 production matched that of misses (failures of the oxygen (O2 ) evolving complex to advance an S-state). Photoinhibition in vitro and in vivo (also in Synechocystis), and in the presence or absence of O2 , had the same temperature dependence, but ultraviolet (UV)-radiation-caused photoinhibition showed a weaker temperature response. We suggest that the miss-associated recombination of P680 + QA - is the main producer of 1 O2 . Our results indicate three parallel photoinhibition mechanisms. The manganese mechanism dominates in UV radiation but also functions in white light. Mechanisms that depend on light absorption by Chls, having 1 O2 or long-lived P680 + as damaging agents, dominate in red light.


A review on microalgal-bacterial co-culture: The multifaceted role of beneficial bacteria towards enhancement of microalgal metabolite production.
Mass microalgal-bacterial co-cultures have come to the fore of applied physiological research, in particularly for the optimization of high-value metabolite from microalgae. These co-cultures rely on the existence of a phycosphere which harbors unique cross-kingdom associations that are a prerequisite for the cooperative interactions. However, detailed mechanisms underpinning the beneficial bacterial effects onto microalgal growth and metabolic production are rather limited at the moment. Hence, the main purpose of this review is to shed light on how bacteria fuels microalgal metabolism or vice versa during mutualistic interactions, building upon the phycosphere which is a hotspot for chemical exchange. Nutrients exchange and signal transduction between two not only increase the algal productivity, but also facilitate in the degradation of bio-products and elevate the host defense ability. Main chemical mediators such as photosynthetic oxygen, N-acyl-homoserine lactone, siderophore and vitamin B12 were identified to elucidate beneficial cascading effects from the bacteria towards microalgal metabolites. In terms of applications, the enhancement of soluble microalgal metabolites is often associated with bacteria-mediated cell autolysis while bacterial bio-flocculants can aid in microalgal biomass harvesting. In addition, this review goes in depth into the discussion on enzyme-based communication via metabolic engineering such as gene modification, cellular metabolic pathway fine-tuning, over expression of target enzymes, and diversion of flux toward key metabolites. Furthermore, possible challenges and recommendations aimed at stimulating microalgal metabolite production are outlined. As more evidence emerges regarding the multifaceted role of beneficial bacteria, it will be crucial to incorporate these findings into the development of algal biotechnology.


Facing adenocarcinoma of distal esophagus and esophagogastric junction: a CROSS versus FLOT propensity score-matched analysis of oncological outcomes in a high-volume institution.
Multimodality treatments are the gold standard for advanced resectable gastroesophageal cancer. Neoadjuvant CROSS and perioperative FLOT regimens are adopted for distal esophageal and esophagogastric junction adenocarcinoma (DE/EGJ AC). At present, none of the approaches is clearly superior in the context of a curative-intent multimodal treatment. We analyzed consecutive patients treated with CROSS or FLOT and surgery for DE/EGJ AC between August 2017 and October 2021. Propensity score matching was performed to balance baseline characteristics of patients. The primary endpoint was disease-free survival. Secondary endpoints included overall survival, 90-day morbidity/mortality rates, pathological complete response, margin-negative resection, and pattern of recurrence. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. The 2-year DFS rate was 54.2% versus 64.1% in the CROSS and FLOT group, respectively (p = 0.182). Patients in the CROSS group showed a lower number of harvested LN when compared to the FLOT group (29.5 versus 39.0 respectively, p = 0.005). A higher rate of distal nodal recurrence was found in the CROSS group (23.8% versus 4.8%, p = 0.026). Although not significant, the CROSS group showed a trend toward higher rate of isolated distant recurrence (33.3% versus 21.4% respectively, p = 0.328), together with a higher rate of early recurrence (23.8% versus 9.5% respectively, p = 0.062). FLOT and CROSS regimens for DE/EGJ AC offer similar DFS and OS, together with comparable morbidity/mortality rates. CROSS regimen was associated with a higher distant nodal recurrence rate. Results of ongoing randomized clinical trials are awaited.


Retention of pacemaker electrode complicated by Serratia marcescens septicemia. Removal with total cardiopulmonary bypass.
A case in which Serratia marcescens septicemia complicated the insertion of a transvernous pacemaker unit is reported. Appropriate antibiotic therapy and removal of the pacemaker electrode are two essential steps to achieve a complete cure in this stimulation. Open cardiotomy with total cardiopulmonary bypass provides a safe approach for withdrawal of an incarcerated electrode and is justified because of the lethal potential of systemic Serratia infections, particularly those superimposed on intracardiac prostheses.


Association of COVID-19 Incidence and Mortality Rates With School Reopening in Brazil During the COVID-19 Pandemic.
School closures because of COVID-19 have left 1.6 billion students around the world without in-person classes for a prolonged period. To our knowledge, no study has documented whether reopening schools in low- and middle-income countries during the pandemic was associated with increased aggregate COVID-19 incidence and mortality with appropriate counterfactuals. To test whether reopening schools under appropriate protocols during the COVID-19 pandemic was associated with increased municipal-level COVID-19 cases and deaths in São Paulo State, Brazil. This observational study of municipalities in São Paulo State, Brazil, uses a difference-in-differences analysis to examine the association between municipal decisions to reopen schools during the COVID-19 pandemic and municipal-level COVID-19 case and death rates between October and December 2020. The study compared 129 municipalities that reopened schools in 2020 with 514 that did not and excluded data for 2 municipalities that reopened schools and closed then again. New COVID-19 cases and deaths per 10 000 inhabitants up to 12 weeks after school reopenings and municipal-level aggregate mobility for a subset of municipalities. There were 8764 schools in the 129 municipalities that reopened schools compared with 9997 in the control group of 514 municipalities that did not reopen schools. The municipalities that reopened schools had a cumulative COVID-19 incidence of 20 cases per 1000 inhabitants and mortality of 0.5 deaths per 1000 inhabitants in September 2020 (the baseline period) compared with an incidence of 18 cases per 1000 inhabitants and mortality of 0.45 deaths per 1000 inhabitants during the baseline period in the comparison group. The findings indicated that there were no statistically significant differences between municipalities that authorized schools to reopen and those that did not for (1) weekly new cases (difference-in-differences, -0.03; 95% CI, -0.09 to 0.03) and (2) weekly new deaths (difference-in-differences, -0.003; 95% CI, -0.011 to 0.004) before and after October 2020. Reopening schools was not associated with higher disease activity, even in relatively vulnerable municipalities, nor aggregate mobility. The findings from this study suggest that keeping schools open during the COVID-19 pandemic did not contribute to the aggregate disease activity.


Cell clones and pattern formation: Developmental restrictions in the compound eye ofDrosophila.
Five regions of the compound eye have been found to be preferential boundaries for clones of labelledMinute + cells, and to act restrictively on the growth of cell clones after a given developmental stage. One of these regions is topographically related to the line of pattern inversion existing at the level of the equator. The results of experiments showing independency of origin of restriction lines and line of pattern inversion are reported.


Seasonal changes in recombination characteristics in a natural population of Drosophila melanogaster.
Environmental seasonality is a potent evolutionary force, capable of maintaining polymorphism, promoting phenotypic plasticity and causing bet-hedging. In Drosophila, environmental seasonality has been reported to affect life-history traits, tolerance to abiotic stressors and immunity. Oscillations in frequencies of alleles underlying fitness-related traits were also documented alongside SNPs across the genome. Here, we test for seasonal changes in two recombination characteristics, crossover rate and crossover interference, in a natural D. melanogaster population from India using morphological markers of the three major chromosomes. We show that winter flies, collected after the dry season, have significantly higher desiccation tolerance than their autumn counterparts. This difference proved to hold also for hybrids with three independent marker stocks, suggesting its genetic rather than plastic nature. Significant between-season changes are documented for crossover rate (in 9 of 13 studied intervals) and crossover interference (in four of eight studied pairs of intervals); both single and double crossovers were usually more frequent in the winter cohort. The winter flies also display weaker plasticity of both recombination characteristics to desiccation. We ascribe the observed differences to indirect selection on recombination caused by directional selection on desiccation tolerance. Our findings suggest that changes in recombination characteristics can arise even after a short period of seasonal adaptation (~8-10 generations).


Ablation of Long Noncoding RNA Hoxb3os Exacerbates Cystogenesis in Mouse Polycystic Kidney Disease.
ADPKD is a monogenic disorder characterized by the formation of kidney cysts and is primarily caused by mutations in two genes, PKD1 and PKD2 . In this study, we investigated the role of lncRNA Hoxb3os in ADPKD by ablating its expression in the mouse. Hoxb3os -null mice were viable and had grossly normal kidney morphology but displayed activation of mTOR/Akt signaling and subsequent increase in kidney cell proliferation. To determine the role of Hoxb3os in cystogenesis, we crossed the Hoxb3os -null mouse to two orthologous Pkd1 mouse models: Pkhd1/Cre; Pkd1F/F (rapid cyst progression) and Pkd1RC/RC (slow cyst progression). Ablation of Hoxb3os exacerbated cyst growth in both models. To gain insight into the mechanism whereby Hoxb3os inhibition promotes cystogenesis, we performed western blot analysis of mTOR/Akt pathway between Pkd1 single-knockout and Pkd1 - Hoxb3os double-knockout (DKO) mice. Compared with single-knockout, DKO mice presented with enhanced levels of total and phosphorylated Rictor. This was accompanied by increased phosphorylation of Akt at Ser 473 , a known mTORC2 effector site. Physiologically, kidneys from DKO mice displayed between 50% and 60% increase in cell proliferation and cyst number. The results from this study indicate that ablation of Hoxb3os in mouse PKD exacerbates cystogenesis and dysregulates mTORC2.


Nomenclatural changes in the higher classification of the family Tettigometridae (Hemiptera: Fulgoroidea) with description of a new tribe and new species and a review of the Iranian tettigometrid fauna.
The first part of this paper provides a historical review of the classification of the family Tettigometridae, including the description of a new tribe, Plesiometrini trib. nov. to accommodate three Afrotropical genera of the subfamily Tettigometrinae. The name Nototettigometra Muir 1924, is proposed to replace Hilda Kirkaldy 1900, homonym of Hilda Hörnes Auinger 1884, and corresponding new combinations are given, including Nototettigometrinae nom. subst. to replace Hildinae Fennah 1952. An identification key to suprageneric taxa of Tettigometridae including both male and female characters is provided. In the second part, 18 tettigometrid species are recorded from Iran. A new species, Tettigometra (Tettigometra) parihana sp. nov. is described. Tettigometra (Metroplaca) longicornis and Tettigometra (Tettigometra) impressifrons are reported as new records for the Iranian fauna. An identification key and distribution maps are provided for the Iran fauna.


Reassessing career pathways of surgical leaders: An examination of surgical leaders' early accomplishments.
The American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and Society of Black Academic Surgeons (SBAS) partnered to gain insight into whether inequities found in surgical society presidents may be present earlier. ACS, ASA, AWS, and SBAS presidents' CVs were assessed for demographics and scholastic achievements at the time of first faculty appointment. Regression analyses controlling for age were performed to determine relative differences across societies. 66 of the 68 presidents' CVs were received and assessed (97% response rate). 50% of AWS future presidents were hired as Instructors rather than Assistant professors, compared to 29.4% of SBAS, 25% of ASA and 29.4% of ACS. The future ACS, ASA, and SBAS presidents had more total publications than the AWS presidents, but similar numbers of 1st and Sr. author publications. Gender inequities in academic surgeon hiring practices and perceived scholastic success may be present at first hire.


Influence of ozone microbubble enhanced oxidation on mine effluent mixes and Daphnia magna toxicity.
The mining industry often must mix different kinds of water on the mine site during pre-treatment or post-treatment before the final discharge of the treated water to the environment. Microbubble ozonation has proven to be efficient in the removal of contaminants of concern from mine water, such as metals, metalloids, and nitrogen compounds, which can persist in the environment and entail toxicity issues. This study evaluated the efficiency of ozone microbubbles combined with lime precipitation on contaminant removal and its impact on toxicity for Daphnia magna with five different mine effluent mixes from an active mine site located in Abitibi-Témiscamingue, QC, Canada. For the non-acidic mixes, two scenarios were tested: first, pre-treatment of metals using lime precipitation and a flocculant was conducted prior to ozonation; and second, ozonation was conducted prior to metals post-treatment using the same precipitation and flocculation technique. Results showed that the NH3-N removal efficiency ranged from 90% for the lower initial concentrations (1.1 mg/L) to more than 99% for the higher initial concentrations (58.4 mg/L). Moreover, ozonation without metals pre-treatment improved NH3-N treatment efficiency in terms of kinetics but entailed abnormal toxicity issues. Results of bioassays conducted on water with metals pre-treatment did not show any toxicity events but showed abnormal toxicity patterns on the mixes treated without metals pre-treatment (diluted effluents were toxic, while undiluted were not). At 50% dilution, the water was toxic, probably due to the potential presence of metal oxide nanoparticles. The confirmation of the source of toxicity requires further investigation.


Radical scavenging activity of bisbenzylisoquinoline alkaloids and traditional prophylactics against chemotherapy-induced oral mucositis.
Oral mucositis is a major severe toxic side-effect of systemic chemotherapy and irradiation in patients with cancer. Various free radical scavengers have been shown to prevent chemotherapy-induced skin necrosis. The objective of this study was to determine the antioxidant activity of a bisbenzylisoquinoline alkaloidal compound (BIQAC) and a series of chemicals, including allopurinol, used clinically for the treatment of chemotherapy-induced mucositis. Allopurinol, melatonin, camostat mesilate, gabexate mesilate, hydroquinone and BIQAC were tested for their radical scavenging activities on four different radical species: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) cation radical (ABTS(*+)) using standard methods, and superoxide anion radical (O(2) (-)) and hydroxyl radical (OH(*)) using electron spin resonance. Allopurinol had radical scavenging activity against O(2) (-) only. Melatonin had strong radical scavenging activity against ABTS(*+), and weak activity against DPPH radical and OH(*). Camostat mesilate had weak radical scavenging activity against OH(*). Gabexate mesilate had no radical scavenging activity against any of these radicals. Hydroquinone had strong radical scavenging activity against DPPH radical and ABTS(*+), and moderate activity against both O(2) (-) and OH(*). BIQAC had moderate radical scavenging activity against DPPH radical, strong radical scavenging activity against ABTS(*+) and O(2) (-), and weak activity against OH(*). The BIQAC had the most braod-spectrum radical scavenging activity, suggesting that it may be effective against chemotherapy-induced mucositis. These findings also suggest that this radical-scavenging activity screening method, against four kinds of radicals, may be useful for the screening of radical scavenging activity of new natural and synthetic chemicals.


Exploring the status of and demand for palliative day-care clinics and day hospices in Germany: a protocol for a mixed-methods study.
To date, the establishment and development of palliative day-care clinics and day hospices in Germany have been completely unsystematic. Research is needed to gain insight into these services and to ensure their accessibility and quality. Accordingly, the ABPATITE research project aims at: (1) identifying the characteristics of palliative day-care clinics and day hospices in Germany, (2) determining demand and preferences for these services, and (3) proposing recommendations (with expert agreement) for the needs-based establishment and development of these services. The research is a multi-perspective, prospective, observational study following a mixed-methods approach across three study phases. In phase 1a, qualitative expert interviews will be conducted to capture the facility-related characteristics of palliative day-care clinics and day hospices in Germany; the results will feed into a questionnaire sent to all such institutions identified nationwide. In phase 1b, a questionnaire will be sent to local statutory health insurance providers, to gain insight into their contracts and accounting and remuneration models. In phase 2a, a service preference survey will be conducted with patients and family caregivers. In phase 2b, semi-structured interviews with management staff will explore the factors that promote and hinder the provision of service. In phase 2c, the external perspective will be surveyed via focus groups with local actors involved in hospice and palliative care. In phase 3a, focus groups with representatives from relevant areas will be conducted to develop recommendations. Finally, in phase 3b, recommendations will be agreed upon through a Delphi survey. The empirically developed recommendations should enable the establishment and development of day hospices and palliative day-care clinics in Germany to be better managed, more oriented to actual demand, and more effectively integrated into wider health care services. Importantly, the findings are expected to optimize the overall development of hospice and palliative care services. The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00021446; date of registration: April 20, 2020). The study is searchable under the International Clinical Trials Registry Platform Search Portal of the World Health Organization, under the German Clinical Trials Register number.


The Black and White of infant back sleeping and infant bed sharing in Florida, 2004-2005.
Not using the infant back sleep position is an established risk factor for sudden unexpected infant death (SUID). Infant bed sharing may also increase SUID risk, particularly under certain circumstances. Both of these infant sleeping behaviors are disproportionately higher among Black mothers. We explored the relationship between not using the infant back sleeping and infant bed sharing, developed separate risk factor profiles for these behaviors, and identified maternal characteristics contributing to racial differences in their practice. Merged 2004-2005 birth certificate and Pregnancy Risk Assessment Monitoring System data for 2,791 non-Hispanic Black and White Florida women were evaluated using univariable and multivariable analyses to develop risk factor profiles for infrequent back sleeping and frequent bed sharing. Cross-product interaction terms were introduced to identify factors contributing to racial differences. Infrequent back sleeping and frequent bed sharing were reported by two-thirds of Black women and one-third of White women. There was no association between the infant sleeping behaviors when adjusted for race (adjusted odds ratio [aOR], 1.04; 95% CI, 0.83-1.31). The infant sleeping behaviors shared no common independent maternal characteristics. Father acknowledgement on the birth certificate was a strong contributor to racial differences in infrequent back sleeping while breastfeeding, trimester of entry to prenatal care, and maternal depression revealed notable racial differences for bed sharing. Behavior-specific and race-specific public health messages may be an important public health strategy for reducing risky infant sleeping behaviors and decreasing SUIDs.


Critical preparedness and operational response actions directed for the acute and post-acute COVID-19 pandemic in Brazil: the experience of a nationwide outpatient healthcare group.
While the new Coronavirus Disease 2019 (COVID-19) pandemic rapidly spread across the world, South America was reached later in relation to Asia, Europe and the United States of America (USA). Brazil concentrates now the largest number of cases in the continent and, as the disease speedily progressed throughout the country, prompt and challenging operational strategies had to be taken by institutions caring for COVID-19 and non-COVID-19 patients in order to assure optimal workflows, triage, and management. Although hospitals in the USA, Europe and Asia have shared their experience on this subject, little has been discussed about such strategies in South America or by the perspective of outpatient centers, which are paramount in the radiology field. This article shares the guidelines adopted early in the pandemic by a nationwide outpatient healthcare center composed by a network of more than 200 patient service centers and nearly 2,000 radiologists in Brazil, discussing operational and patient management strategies, staff protection, changes adopted in the fellowship program, and the effectiveness of such measures.


Missense mutation in GRN gene affecting RNA splicing and plasma progranulin level in a family affected by frontotemporal lobar degeneration.
Gene coding for progranulin, GRN, is a major gene linked to frontotemporal lobar degeneration. While most of pathogenic GRN mutations are null mutations leading to haploinsufficiency, GRN missense mutations do not have an obvious pathogenicity, and only a few have been revealed to act through different pathogenetic mechanisms, such as cytoplasmic missorting, protein degradation, and abnormal cleavage by elastase. The aim of this study was to disclose the pathogenetic mechanisms of the GRN A199V missense mutation, which was previously reported not to alter physiological progranulin features but was associated with a reduced plasma progranulin level. After investigating the family pedigree, we performed genetic and biochemical analysis on its members and performed RNA expression studies. We found that the mutation segregates with the disease and discovered that its pathogenic feature is the alteration of GRN mRNA splicing, actually leading to haploinsufficiency. Thus, when facing with a missense GRN mutation, its pathogenetic effects should be investigated, especially if associated with low plasma progranulin levels, to determine its nature of either benign polymorphism or pathogenic mutation.


Generation and Functional Characterization of PLAP CAR-T Cells against Cervical Cancer Cells.
Chimeric antigen receptor (CAR) T-cell therapy is one of the cancer treatment modalities that has recently shown promising results in treating hematopoietic malignancies. However, one of the obstacles that need to be addressed in solid tumors is the on-target and off-tumor cytotoxicity due to the lack of specific tumor antigens with low expression in healthy cells. Placental alkaline phosphatase (PLAP) is a shared placenta- and tumor-associated antigen (TAA) that is expressed in ovarian, cervical, colorectal, and prostate cancers and is negligible in normal cells. In this study, we constructed second-generation CAR T cells with a fully human scFv against PLAP antigen andthen evaluated the characteristics of PLAP CAR T cells in terms of tonic signaling and differentiation in comparison with ΔPLAP CAR T cells and CD19 CAR T cells. In addition, by co-culturing PLAP CAR T cells with HeLa and CaSki cells, we analyzed the tumor-killing functions and the secretion of anti-tumor molecules. Results showed that PLAP CAR T cells not only proliferated during co-culture with cancer cells but also eliminated them in vitro. We also observed increased secretion of IL-2, granzyme A, and IFN-γ by PLAP CAR T cells upon exposure to the target cells. In conclusion, PLAP CAR T cells are potential candidates for further investigation in cervical cancer and, potentially, other solid tumors.


Implication of American Society of Anesthesiologists Physical Status (ASA-PS) on tonsillectomy with or without adenoidectomy outcomes.
The American Society of Anesthesiologists Physical status classification (ASA-PS) is a simple categorization of a patient's physiological status during the perioperative period. The role of ASA-PS in predicting operative risk and complications following tonsillectomy with or without adenoidectomy (T ± A) has not been studied. The objective of the study was to identify the association of the pre-operative ASA-PS with 30-day complication rates and adverse events following T ± A. A retrospective analysis was performed using data from the American College of Surgeons' National Surgical Quality Improvement Program database (ACS NSQIP) of patients aged 16 years or older who underwent T ± A between 2005 and 2016. Patients were stratified into ASA-PS Classes I/II and III/IV. Patient demographics, preoperative comorbidities, pre-operative laboratory values, operation-specific variables, and postoperative outcomes in the 30-day period following surgery were compared between the two subsets of ASA-PS groups. On multivariate analysis, patients with ASA class III and IV were more likely to experience an unplanned readmission (OR 1.39, 95 % CI 1.09-1.76; p = 0.007), overall complications (OR 1.49, 95 % CI 1.28-1.72; p < 0.001), major complications (OR 1.52, 95 % CI 1.31-1.77, p ≤ 0.001), reoperation (OR 1.33, 95 % CI 1.04-1.69; p = 0.022), and extended length of stay >1 day (OR 1.78, 95 % CI 1.41-2.25; p < 0.001) following a T ± A. Higher ASA-PS classification is an independent predictor of complications following T ± A. Surgeons should aim to optimize the systemic medical conditions of ASA-PS classes III and IV patients prior to T ± A and implement post-operative management protocols specific to these patients to decrease morbidity, complications, and overall health care cost.


Immunizing in a Global Society: Vaccines for Travelers.
The risk of travel-related illnesses that require vaccines varies depending on destination and traveler characteristics. Travelers who are not immune and going to countries and regions with endemic diseases are at risk of contracting vaccine-preventable diseases; they can serve as conduits of the disease on return to their home country. Individual travelers can work with a health care professional to assess travel risk based on diseases endemic to the region, time of year of travel, and presence of acute outbreaks. Travelers should discuss personal medical history, immunization status, purpose of trip, and other individual risk factors to help determine which vaccines they need.


A compartmentalized microsystem helps understanding the uptake of benzo[a]pyrene by fungi during soil bioremediation processes.
Hydrophobic organic soil contaminants such as polycyclic aromatic hydrocarbons (PAH) are poorly mobile in the aqueous phase and tend to sorb to the soil matrix, resulting in low bioavailability. Some filamentous fungi are efficient in degrading this kind of pollutants. However, the mechanism of mobilization of hydrophobic compounds by non-motile microorganisms such as filamentous fungi needs investigations to improve pollutant bioavailability and bioremediation efficiency. Usual homogeneous media for microbial growth in the lab are poorly suited to model the soil, which is a compartmentalized and heterogeneous habitat. A microfluidic device was designed to implement a compartmentalization of the fungal inoculum and the source of the pollutant benzo[a]pyrene (BaP) as a deposit of solid crystals in order to gain a further insight into the mechanisms involved in the access to the contaminant and its uptake in soils. Thus in this device, two chambers are connected by an array of parallel microchannels that are wide enough to allow individual hyphae to grow through them. Macro-cultures of Talaromyces helicus in direct contact with BaP have shown its uptake and intracellular storage in lipid bodies despite the low propensity of BaP to cross aqueous phases as shown by simulation. Observations of T. helicus in the microfluidic device through laser scanning confocal microscopy indicate preferential uptake of BaP at a close range and through contact with the cell wall. However faint staining of some hyphae before contact with the deposit also suggests an extracellular transport phenomenon. Macro-culture filtrates analyses have shown that T. helicus releases extracellular non-lipidic surface-active compounds able to lower the surface tension of culture filtrates to 49.4 mN/m. Thus, these results highlight the significance of active mechanisms to reach hydrophobic contaminants before their uptake by filamentous fungi in compartmentalized micro-environments and the potential to improve them through biostimulation approaches for soil mycoremediation.


Embryo toxicity of clomiphene citrate on mouse embryos fertilized in vitro and in vivo.
The effect of the ovulatory agent clomiphene citrate on fertilization and early embryogenesis was investigated with the use of in vitro fertilized mouse oocytes. Alterations in early embryogenesis with clomiphene citrate exposure were further studied with the use of embryos obtained from mouse oocytes fertilized in vivo. In the nontreated group, the fertilization rate was 81%, and 61% of the oocytes reached the blastocyst stage by 96 hours. Both fertilization and blastocyst formation declined in a dose-dependent fashion when clomiphene citrate was added to the culture media in concentrations greater than or equal to 10 micrograms/ml (p less than 0.001). The rate of progressive embryo cleavage was also slower at 48 and 72 hours after drug exposure. Mouse embryos fertilized in vivo demonstrated similar findings, with decreased blastocyst formation and increased degeneration rates, again at clomiphene citrate concentrations greater than or equal to 10 micrograms/ml (p less than 0.01). Exposure to the drug beyond 24 hours had no additional effect. It appears that clomiphene citrate-exposed embryos may undergo subtle changes that later manifest themselves in the form of decreased embryo growth rates and increased embryo degeneration rates.


Structural studies on the hexose region of the Enterobacteriaceae type R3 core polysaccharide.
The structure of the hexose region of the Enterobacteriaceae type R3 core polysaccharide, which is the common core in Shigella flexneri and some Escherichia coli lipopolysaccharides (LPS), has been investigated. The principal method used in these studies involved methylation analysis of the original and modified materials. The polysaccharide was modified by N-deacetylation-deamination and by Smith degradation. As a result of these studies, the following structure is proposed: alpha-D-Glcp-(1 leads to 2)-alpha-D-Glcp-(1 leads to 2)-[alpha-D-GlcNAcp-(1 leads to 3)]-alpha-D-Galp-(1 leads to 3)-alpha-D-Glcp-(1 leads to.


Interactions of analgesics with other drugs.
Antipyretic analgesics, such as salicylates, acetaminophen, and pyrazolones, are often given concomitantly with a variety of other drugs. Drug interactions that occur at the receptors are known as pharmacodynamic interactions; alterations in absorption (bioavailability), distribution (plasma protein-binding), and elimination (renal excretion, hepatic metabolism) are termed pharmacokinetic interactions. For example, antacids and food both delay the absorption of analgesics. Highly protein-bound drugs (such as phenylbutazone, phenytoin, or warfarin) can compete with the common binding sites of salicylates. Hepatic elimination of salicylates can be influenced by drugs such as beta-blockers and cimetidine. Clinically important interactions involving salicylates, acetaminophen, and other antipyretic analgesics are discussed.


Identification of an HLA-A24-restricted OY-TES-1 epitope recognized by cytotoxic T-cells.
OY-TES-1 was identified as a human homologue of the mouse, guinea pig, and pig proacrosin binding protein sp32 precursor. Differential expression levels of OY-TES-1 mRNA between testis and other normal tissues, and its expression in cancers indicated that OY-TES-1 would be classified as a cancer/testis antigen and considered to be a candidate of target antigen for cancer immunotherapy. In this study, we showed identification of HLA-A24-binding OY-TES-1 peptide, TES(401-409) (KTPFVSPLL) recognized by CD8 T-cells. Purified CD8 T-cells from healthy donors stimulated in vitro with the peptide-pulsed autologous DC and PBMC produced IFNgamma in response to the peptide-pulsed PBMC and showed cytotoxicity against the peptide-pulsed autologous EBV-B specifically. Furthermore, cytotoxicity was also observed against an OY-TES-1 mRNA-expressing tumor line, LK79. The retention time of the fraction in HPLC of the acid eluate from LK79 cells that showed positive sensitization against autologous EBV-B cells in recognition by CD8 CTL was the same as that of the fraction of the TES(401-409) peptide itself, suggesting that the TES(401-409) was a naturally processed peptide on LK79.