Dose-response relationship between dietary antioxidant intake and diabetic kidney disease in the US adults with diabetes.
The effects of dietary antioxidants on numerous diseases have been widely studied. However, the evidence regarding composite dietary antioxidant index (CDAI) and diabetic kidney disease (DKD) in individuals with diabetes is scarce. This study aimed to investigate the associations of CDAI with DKD and mortality in adults with diabetes mellitus (DM). This study utilized data from 5676 adult DM participants from the National Health and Nutrition Examination Survey (NHANES) of 2007-2018. The study followed up on death outcomes by linking the data to records from the National Death Index until December 31, 2019. CDAI was evaluated using a well-established method that included six food-sourced antioxidants derived from 24-h dietary recall: selenium, zinc, vitamin A, vitamin C, vitamin E and carotenoids. The regression models were used to estimate the relationships of CDAI with DKD and mortality in diabetic individuals. The weighted mean CDAI level for the 5676 participants, which represented 31.36 million noninstitutionalized residents of the US, was 0.33. Based on CDAI quartiles, participants were classified into four groups. CDAI levels were significantly associated with age, gender, race, physical activity, estimated glomerular filtration rate and the prevalence of albuminuria, DKD and hyperuricemia. DKD occurred in 36.44% of diabetic participants, and higher CDAI levels were independently associated with a lower risk of DKD (OR 0.74, 95%CI 0.59-0.94, p for trend = 0.004) in diabetic individuals after multivariate adjustment. During a median follow-up of 67 months (38-104 months), a total of 1065 (15.80%) diabetic individuals died from all causes. Diabetic individuals with higher CDAI levels (Q4) demonstrated a lower risk of all-cause mortality (HR 0.67, 95% CI: 0.52-0.86, p for trend = 0.01) after adjusting for age, gender and race. Maintaining an adequate antioxidant diet, as reflected in higher CDAI levels, may lower the risk of DKD and mortality in diabetic individuals. These findings offer a promising approach to managing diabetes and highlight the potential of food-based antioxidants as a preventative measure. Further research is warranted to explore the underlying mechanism linking dietary antioxidants and DKD and mortality in diabetic individuals.


Nanoparticles in modern medicine: state of the art and future challenges.
Nanoparticles are materials with overall dimensions in the nanoscale, ie, under 100 nm. In recent years, these materials have emerged as important players in modem medicine, with clinical applications ranging from contrast agents in imaging to carriers for drug and gene delivery into tumors. Indeed, there are some instances where nanoparticles enable analyses and therapies that simply cannot be performed otherwise. However, nanoparticles also bring with them unique environmental and societal challenges, particularly in regard to toxicity. This review aims to highlight the major contributions of nanoparticles to modem medicine and also discuss environmental and societal aspects of their use.


Targeted microarray analysis of stationary phase Escherichia coli O157:H7 subjected to disparate nutrient conditions.
To determine how stress response and virulence gene expression of stationary phase (SP) Escherichia coli O157:H7 are affected by nutrient levels. A targeted microarray (n=125 genes) was used to determine the impact of nutrient deprivation [15 min in 3-(N-Morpholino)propanesulfonic acid buffer] on SP E. coli O157:H7. In total, 24 genes were significantly affected (>1·5-fold; P <0·05) with 17 induced and seven attenuated. Additionally, 11 genes belonging to significantly affected stress response regulons were significantly induced (P<0·05), though <1·5-fold. Induced genes included global and specific stress response regulators, the mar operon, iron acquisition and virulence genes. In contrast, transcript for major porins and replicative genes were repressed. Comparison of the nutrient deprived transcriptome to that derived from nutrient replenished cells revealed a disparate transcriptome, with 44 genes expressed at significantly elevated levels in nutrient replenished cells, including all queried global and specific stress response regulators and key virulence genes. Genes expressed at elevated levels in nutrient deprived cells were related to σ(S) . The microarray data were validated by qRT-PCR. SP E. coli O157:H7 were affected by nutrient deprivation, with both starvation-related and unrelated networks induced, thereby demonstrating how the E. coli O157:H7 stress response transcriptome is fine-tuned to environmental conditions. Further, by comparison of starved cells to cells provided with fresh nutrients, it is clear starved E. coli O157:H7 undergo massive physiological reprogramming dominated initially by stress response induction to adapt to a nutrient rich environment. This study demonstrated how σ(S) -induced SP E. coli O157:H7 remain highly sensitive and adaptable to environmental conditions. Further, by examining how starved cells respond to nutrient-rich conditions, we show preliminary adaptation to a nutrient rich environment is dominated by the induction of diverse stress response networks. Combined, this provides E. coli O157:H7 stress physiology-based knowledge that can be used to design more effective food safety interventions.


A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma.
A randomized prospective clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated, short course radiotherapy in poor prognosis patients with high grade glioma. The primary endpoint was overall survival.


Gender differences on chest pain perception associated with acute myocardial infarction in Chinese patients: a questionnaire survey.
To investigate gender differences in chest pain perception among Chinese patients with acute myocardial infarction. Thrombolytic therapy is beneficial to outcomes of acute myocardial infarction if administered within 12 hours from the onset of chest pain. However, cardiac symptom interpretation may impact time of presentation to hospital. Differences in cardiac symptom reports by gender partly explain misdiagnoses and delays in treatment, particularly among women. Whether, such trends apply to Chinese patients with myocardial infarction is unknown. A descriptive prospective study. Using questionnaires, data on demographic variables, the number of patients reporting chest pain and other chest sensations at the onset of acute myocardial infarction and chest pain intensity, description, location and radiation across the chest were collected. A total of 128 participants equally divided by gender were recruited. Chest pain was more prevalent among men than women (84.37% vs. 67.19%, p < 0.05). Although no statistical significance was found, Chinese men had higher mean chest pain intensity scores (7.54 SD 2.35 vs. 7.51 SD 2.25) and reported less atypical chest pain (0.00% vs. 9.3%) compared with women. Men had more upper right sided chest pain (40.74% vs. 20.93%, p = 0.038) whereas women experienced increased neck pain and pain to the upper central chest, middle central chest, upper central back, middle central back and middle right back regions. Discreet gender differences in chest pain perceptions exist between Chinese men and women, with the latter group, who may be considered as a high-risk group for missed and delayed diagnosis from myocardial infarction, reporting more atypical presentations. Irrespective of culture, women with myocardial infarction tend to present with atypical chest pain symptoms and therefore they should be aggressively investigated.


Landscape change and ecosystem classification in a municipal district of a small city (Isernia, Central Italy).
Landscape changes taking place from 1954 to 1992 in the muncipal district of Isernia city (Central Italy) were described in relation to a system of ecosystem classification. Isernia municipal district was selected for study because recent historic changes in this area represent a typical example of landscape transformation similar to many small cities of Italy and other Mediterranean countries. To assess overall changes, three land cover maps (scale 1:25,000) were derived from panchromatic aerial photographs and field surveys. These were then digitalised in a Geographic Information System. A Land Facet (LF) map was derived by combining a phytoclimatic, a lithostatigrafic and a topographic map, and then digitalised as data layers in the same GIS. Results demonstrated two main landscape transformation trends: forest and semi-natural areas increased (8%), whereas agricultural areas decreased (12%). The urban area was relatively small during the entire analysed period, growing from 1% in 1954, to just 5% in 1992. Forest coverage was significant on reliefs, on hillside ecosystems such as limestone and on clay and marl hills LF. Arable land was particularly significant in flat ecosystems with deeper soils, such as on recent alluvial plain LF. These temporal changes were interpreted as being related to the replacement of traditional farming methods (grazing pastures) with more intensive methods (crop fields), especially on alluvial plains.


Diabetes mellitus and prostate cancer risk.
Epidemiological evidence suggests that diabetes mellitus (DM) is associated with a decrease in risk for prostate cancer (PCa). The objective of this study was to examine the association between PCa risk and several characteristics of DM (duration, age at diagnosis, treatment) in data from two population-based, case-control studies of PCa. PCa cases (n = 1,752), and controls (n = 1,644) were residents of King County, Washington identified using the Surveillance, Epidemiology, and End Results Seattle-Puget Sound cancer registry and random digit dialing, respectively. The majority of PCa patients had localized stage disease (78%). Using self-reported on DM, logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between DM characteristics and PCa risk. After adjustment for confounding factors, DM status was not significantly associated with PCa risk (OR = 0.98; 95% CI = 0.76-1.27). However, early-onset DM (diagnosed before age 30) showed a significant inverse association with PCa risk (OR = 0.27; 95% CI = 0.07-0.97). Time since DM diagnosis (median = 6 years) and DM treatment types (i.e., diet changes, oral medications, and insulin) did not show significant associations with PCa risk. These data suggest that DM is not associated with PCa risk; however, early-onset DM, possibly reflecting insulin dependent DM (type 1), may be an important component of the previously reported inverse association between DM on PCa risk, but these findings are based on a small number of observations and require further investigation.


Single Trial Plasticity in Evidence Accumulation Underlies Rapid Recalibration to Asynchronous Audiovisual Speech.
Asynchronous arrival of audiovisual information at the peripheral sensory organs is a ubiquitous property of signals in the natural environment due to differences in the propagation time of light and sound. As these cues are constantly changing their distance from the observer, rapid adaptation to asynchronies is crucial for their appropriate integration. We investigated the neural basis of rapid recalibration to asynchronous audiovisual speech in humans using a combination of psychophysics, drift diffusion modeling, and electroencephalography (EEG). Consistent with previous reports, we found that perception of audiovisual temporal synchrony depends on the temporal ordering of the previous trial. Drift diffusion modelling indicated that this recalibration effect is well accounted for by changes in the rate of evidence accumulation (i.e. drift rate). Neural responses as indexed via evoked potentials were similarly found to vary based on the temporal ordering of the previous trial. Within and across subject correlations indicated that the observed changes in drift rate and the modulation of evoked potential magnitude were related. These results indicate that the rate and direction of evidence accumulation are affected by immediate sensory history and that these changes contribute to single trial recalibration to audiovisual temporal asynchrony.


A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance.
Studies have suggested an important connection between epilepsy and Alzheimer's disease (AD), mostly due to the high number of patients diagnosed with AD who develop epileptic seizures later on. However, this link is not well understood. Previous studies from our group have identified memory impairment and metabolic abnormalities in the Wistar audiogenic rat (WAR) strain, a genetic model of epilepsy. Our goal was to investigate AD behavioral and molecular alterations, including brain insulin resistance, in naïve (seizure-free) animals of the WAR strain. We used the Morris water maze (MWM) test to evaluate spatial learning and memory performance and hippocampal tissue to verify possible molecular and immunohistochemical alterations. WARs presented worse performance in the MWM test (p < 0.0001), higher levels of hyperphosphorylated tau (S396) (p < 0.0001) and phosphorylated glycogen synthase kinase 3 (S21/9) (p < 0.05), and lower insulin receptor levels (p < 0.05). Conversely, WARs and Wistar controls present progressive increase in amyloid fibrils (p < 0.0001) and low levels of soluble amyloid-β. Interestingly, the detected alterations were age-dependent, reaching larger differences in aged than in young adult animals. In summary, the present study provides evidence of a partial AD-like phenotype, including altered regulation of insulin signaling, in a genetic model of epilepsy. Together, these data contribute to the understanding of the connection between epilepsy and AD as comorbidities. Moreover, since both tau hyperphosphorylation and altered insulin signaling have already been reported in epilepsy and AD, these two events should be considered as important components in the interconnection between epilepsy and AD pathogenesis and, therefore, potential therapeutic targets in this field.


Orientation of cobra alpha-toxin on the nicotinic acetylcholine receptor. Fluorescence studies.
Four flourescein isothiocyanate (FITC) derivatives of Naja naja siamemsis 3 neurotoxin (alpha-toxin), labeled at the epsilon-amino groups of Lys-23, Lys-35, Lys-49, or Lys-69, and a tetramethylrhodamine isothiocyanate (TRITC) derivative, labeled at epsilon-amino group of Lys-23, were prepared and used to analyze the orientation of cobra alpha-toxin on the nicotinic acetylcholine receptor (AcChR) relative to both the plane of the membrane and the central ion channel. Fluorescence-quenching studies of the AcChR-bound FITC derivatives indicated significant solute accessibility to each site of labeling and suggested that none of the sites of FITC labeling is included in the binding surface of the alpha-toxin. Labeling of Lys-23 with TRITC did not affect the affinity of the alpha-toxin toward the AcChR and confirmed, contrary to some previous reports, a minimal role of Lys-23 in the binding surface of the alpha-toxin. Measurements of energy transfer between the lipid-membrane surface and the sites of labeling on receptor-bound alpha-toxin derivatives show that the relative distances of closest approach between the surface of the lipid membrane domain and the sites of labeling are in the order Lys-23 less than or equal to Lys-49 less than Lys-35 less than or equal to Lys-69. Energy transfer between AcChR tryptophans and the sites of labeling of bound derivatives was about 50% greater to Lys-49 than to Lys-23, Lys-35, or Lys-69, suggesting that Lys-49 is closer to receptor tryptophans and to the center of the extracellular domain of the receptor than Lys-23, Lys-35, or Lys-69. Combined with previous observations that the tip of the central loop of the alpha-toxin directly interacts with the AcChR, the above results suggest a model of the approximate orientation of the snake neurotoxins on the receptor. This model shows the tip of the central loop of the toxin directly interacting with the receptor surface and the major axis of the neurotoxin tilting from a perpendicular projection from the membrane. The surface of the alpha-toxin that includes Lys-23 projects away from the central ion channel and the surface that includes Lys-35 and Lys-69 faces the ion channel.


Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria.
Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.


Impact of government policies on photovoltaic supply chain considering quality in the power distribution system: a case study.
Nowadays, due to the lack of energy and the harmful effects of fossil fuels on the environment, many countries seek to use renewable sources such as solar energy, a clean and free energy source. Direct conversion of solar energy into electricity is the reason for using solar cells. This paper proposes a three-echelon photovoltaic supply chain with two suppliers (domestic and foreign), two power plants (big and small), and a power distribution system with government intervention. We consider three approaches, including (1) the decentralized model, (2) the centralized model, and (3) the government's role in the photovoltaic supply chain. In the first model, the power distribution system is a leader, and other members are followers. In the second model, we explore the whole supply chain as a centralized model, and in the third model, the government has the leading role, and the rest of the members follow. Indeed, in the last model, the role of the government as a supporter that gives subsidies and tax exemptions to keep members in a competitive market is investigated, and the decision variables of the government (tariffs) are obtained. Finally, based on real example from the power industry of Iran, sensitivity analysis and managerial insights are proposed.


Intestinal (mesenteric) vasculopathy. II. Ischemic colitis and chronic mesenteric ischemia.
Ischemic colitis accounts for approximately half of all cases of mesenteric vasculopathy. The clinical presentation varies depending on underlying cause, extent of vascular obstruction, rapidity of ischemic insult, degree of collateral circulation, and presence of comorbidity. Ischemic colitis is usually diagnosed by colonoscopy. Only approximately 20% of patients require surgery because of signs or laboratory findings of peritonitis or because of clinical deterioration. Approximately 20% of patients develop chronic colitis from irreversible colonic ischemic injury, which manifests clinically as persistent diarrhea, rectal bleeding, or weight loss and endoscopically as a colonic stricture or mass. Chronic mesenteric ischemia is almost always caused by significant atherosclerotic stenosis involving at least two mesenteric arteries, usually the superior mesenteric artery and celiac axis. The classic symptomatic triad of postprandial pain, fear of eating, and involuntary weight loss occurs with advanced disease.


Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein.
Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells. Although these hybrids exerted significant inhibition of HL-60 cell proliferation, they showed high cytotoxicity on human normal cells (WI-38). Utilizing information from molecular modelling of the hybrids to the anti-apoptotic Bcl-2 protein, we added substructures including phenyl, piperazine, piperidine, and morpholine rings to their frameworks. The designed quinoxaline-1,3,4-oxadiazole hybrid derivatives successfully induced apoptotic response on HL-60 cells with low toxicity on WI-38 cells. Furthermore, RT-PCR analysis demonstrated that these derivatives predominantly inhibit Bcl-2 expression. Our findings highlight the great potential for the development of synthetic quinoxaline-1,3,4-oxadiazole hybrid derivatives as proapoptotic anticancer agents.


Preclinical efficacy in investigator's brochures: Stakeholders' views on measures to improve completeness and robustness.
Research ethics committees and regulatory agencies assess whether the benefits of a proposed early-stage clinical trial outweigh the risks based on preclinical studies reported in investigator's brochures (IBs). Recent studies have indicated that the reporting of preclinical evidence presented in IBs does not enable proper risk-benefit assessment. We interviewed different stakeholders (regulators, research ethics committee members, preclinical and clinical researchers, ethicists, and metaresearchers) about their views on measures to increase the completeness and robustness of preclinical evidence reporting in IBs. This study was preregistered (https://osf.io/nvzwy/). We used purposive sampling and invited stakeholders to participate in an online semistructured interview between March and June 2021. Themes were derived using inductive content analysis. We used a strengths, weaknesses, opportunities and threats matrix to categorize our findings. Twenty-seven international stakeholders participated. The interviewees pointed to several strengths and opportunities to improve completeness and robustness, mainly more transparent and systematic justifications for the included studies. However, weaknesses and threats were mentioned that could undermine efforts to enable a more thorough assessment: The interviewees stressed that current review practices are sufficient to ensure the safe conduct of first-in-human trials. They feared that changes to the IB structure or review process could overburden stakeholders and slow drug development. In principle, more robust decision-making processes align with the interests of all stakeholders and with many current initiatives to increase the translatability of preclinical research and limit uninformative or ill-justified trials early in the development process. Further research should investigate measures that could be implemented to benefit all stakeholders.


SANS study on the effect of lanthanide ions and charged lipids on the morphology of phospholipid mixtures. Small-angle neutron scattering.
The structural phase behavior of phospholipid mixtures consisting of short-chain (dihexanoyl phosphatidylcholine) and long-chain lipids (dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol), with and without lanthanide ions was investigated by small-angle neutron scattering (SANS). SANS profiles were obtained from 10 degrees C to 55 degrees C using lipid concentrations ranging from 0.0025 g/ml to 0.25 g/ml. The results reveal a wealth of distinct morphologies, including lamellae, multi-lamellar vesicles, unilamellar vesicles, and bicellar disks.


Developing linear ADL ability measures based on the ADL Taxonomy: a Rasch analysis.
The aim of this pilot study was to explore the possibility of developing linear measures of ADL ability based on the ADL Taxonomy and a three-category rating scale. Data were obtained from medical records of adults with moderate to severe brain injury. The participants were rated on the ADL taxonomy, and recorded on the ADL Taxonomy Circle, based on direct observations. By applying the Rasch rating scale model, we examined the possibility of converting the raw ordinal scores into equal-interval estimates of the participants' ADL ability. The data analysis indicated that the rating scale used in this study displays sound psychometric properties. Items from the ADL taxonomy defined one construct after 10 actions were removed, but retention of all items did not disrupt the measurement system. Except for one item in each of five different activity domains, the item difficulty hierarchy was the same as in the hierarchy originally published, supporting reliability of the item difficulty estimates. The ADL taxonomy discriminated well between different levels of ability in this sample of persons with brain injury. This preliminary study indicates that the ADL taxonomy has potential to become a linear measure of a person's ability to perform ADL tasks.


The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.
To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.


A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy.
The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate. Patients with recurrent primary brain tumors with performance status 0-2 were eligible. Intravenous bevacizumab 10 mg/kg and irinotecan 125/340 mg/m(2) were administered every 14 days. Evaluation was carried out every eight weeks using MRI and Macdonald response criteria. Treatment was continued until progression. In total 85 patients were included with the following histologies: GBM (n = 32), glioma WHO gr. III (n = 33), glioma WHO gr. II (n = 12) and others (n = 8). Patients received a median of four cycles. ORR (overall response rate) for glioblastoma was 25% and 59% achieved stable disease (SD). Median PFS was 5.2 months. For grade III gliomas ORR was 21% and 45% had SD. Median PFS was 3.7 months. No objective responses occurred in grade II gliomas. In the non-glioma population, one PR as well as several long PFS times were observed. The combination of bevacizumab and irinotecan is well tolerated and moderately efficacious in glioblastoma and glioma WHO gr. III. A majority of patients achieve at least disease stabilization. Prolonged progression-free survival in non-glioma patients warrants further research.


The Antiphospholipid Syndrome in the Pediatric Population.
Pediatric antiphospholipid syndrome (APS) is characterized by autoantibodies directed against protein complexes on cellular membranes and leads to a prothrombotic, proinflammatory state. A child with APS may present with venous, arterial, or small vessel thrombosis. Other manifestations of APS include nonthrombotic manifestations, such as hematologic and neurologic symptoms. APS may be a primary condition or related to other autoimmune diseases. If APS-related thrombosis is unrecognized, the child may suffer recurrent thrombotic events after the withdrawal of anticoagulation. Thus, it is important to consider APS as a cause of thrombosis in children. Appropriate testing confirms the diagnosis and directs further care.


Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion.
Circadian clocks are functional in all light-sensitive organisms, allowing an adaptation to the external world in anticipation of daily environmental changes. In view of the potential role of the skeletal muscle clock in the regulation of glucose metabolism, we aimed to characterize circadian rhythms in primary human skeletal myotubes and investigate their roles in myokine secretion. We established a system for long-term bioluminescence recording in differentiated human myotubes, employing lentivector gene delivery of the Bmal1-luciferase and Per2-luciferase core clock reporters. Furthermore, we disrupted the circadian clock in skeletal muscle cells by transfecting siRNA targeting CLOCK. Next, we assessed the basal secretion of a large panel of myokines in a circadian manner in the presence or absence of a functional clock. Bioluminescence reporter assays revealed that human skeletal myotubes, synchronized in vitro, exhibit a self-sustained circadian rhythm, which was further confirmed by endogenous core clock transcript expression. Moreover, we demonstrate that the basal secretion of IL-6, IL-8 and MCP-1 by synchronized skeletal myotubes has a circadian profile. Importantly, the secretion of IL-6 and several additional myokines was strongly downregulated upon siClock-mediated clock disruption. Our study provides for the first time evidence that primary human skeletal myotubes possess a high-amplitude cell-autonomous circadian clock, which could be attenuated. Furthermore, this oscillator plays an important role in the regulation of basal myokine secretion by skeletal myotubes.


Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery.
Anti-inflammatory effects of tranexamic acid and aprotinin, used to abate perioperative blood loss, are reported and might be of substantial clinical relevance. The study of messenger ribonucleic acid synthesis provides a valuable asset in evaluating the inflammatory pathways involved. Whole-blood messenger ribonucleic acid expression of 114 inflammatory genes was compared pre- and postoperatively in 35 patients randomized to receive either placebo, tranexamic acid, or aprotinin. These results were further confirmed by reverse transcription-polymerase chain reaction. Of the 23 genes exhibiting independently altered postoperative gene expression levels, 8 were restricted to the aprotinin group only (growth differentiation factor 3, interleukin 19, interleukin 1 family member 7, transforming growth factor α, tumor necrosis factor superfamily 10, tumor necrosis factor superfamily 12, tumor necrosis factor superfamily 13B, vascular endothelial growth factor α), whereas both aprotinin and tranexamic acid altered gene expression of 3 genes as compared with placebo (FMS-related tyrosine kinase 3 ligand, growth differentiation factor 5, interferon-α8). In general, less upregulation of pro-inflammatory, and more upregulation of anti-inflammatory, genes was observed for patients treated with antifibrinolytics. Gene expression affected by aprotinin coded mostly for proteins that function through serine proteases. This study demonstrates that the use of tranexamic acid and aprotinin results in altered inflammatory pathways on the genomic expression level. We further demonstrate that the use of aprotinin leads to significant attenuation of the immune response, with several inhibitory effects restricted to the use of aprotinin only. The results aid in a better understanding of the targets of these drugs, and add to the discussion on which antifibrinolytic can best be used in the cardiac surgical patient.


Protective effect of L-cysteine and glutathione on the modulated suckling rat brain Na+, K+, -ATPase and Mg2+ -ATPase activities induced by the in vitro galactosaemia.
Galactosaemia is an inborn error of galactose (Gal) metabolism characterized by irreversible brain damage. The aim of this study was to evaluate whether the antioxidants L-cysteine (Cys) and the reduced glutathione (GSH) could reverse the alterations of brain total antioxidant status (TAS) and the modulated activities of the enzymes Na+,K+ -ATPase and Mg2+ -ATPase in in vitro galactosaemia. Mixture A (mix. A: galactose-1-phosphate (Gal-1-P, 2mM) plus galactitol (Galtol, 2mM) plus Gal (4mM) = classical galactosaemia) or Mixture B (mix. B: Galtol (2mM) plus Gal (1mM) = galactokinase deficiency galactosaemia) were preincubated in the presence or absence of Cys (0.83mM) or GSH (0.83 mM) with whole brain homogenates of suckling rats at 37 degrees C for 1h. TAS and the enzyme activities were determined spectrophotometrically. The preincubation of brain homogenates with mix. A or mix. B resulted in a decrease of TAS to 30% (P < 0.01), while the presence of Cys or GSH increased TAS to 20% (P < 0.01) and 60% ( P < 0.001), respectively. The antioxidants reversed the inhibited Na+,K+ -ATPase by mix. A or mix. B and the stimulated Mg2+ -ATPase by mix. B to control values, whereas no effect was observed on the enormously activated Mg2+ -ATPase by mix. A. (a) Gal and its derivatives may produce free radicals in the suckling rat brain, reported for first time, (b) Na+,K+ -ATPase inhibition and Mg2+ -ATPase activation are probably due to the oxidative stress from the above compounds, (c) Cys or GSH could play a protective role reversing the inhibited Na+,K+ -ATPase toward normal in in vitro galactosaemia and (d) the addition of the above antioxidants may reduce the consequences of brain Mg2+ -ATPase activation by Gal and Galtol in galactokinase deficiency galactosaemia.


Genome-wide mutational analysis of Chikungunya strains from 2016 to 2017 outbreak of central India: An attempt to elucidate the immunological basis for outbreak.
Chikungunya re-emerged in India in 2016-2017, as the first major outbreak since 2006. In our previous study, we undertook partial E1 gene sequencing and phylogenetic/mutational analysis of strains from the 2016-2017 outbreak of Chikungunya in central India and reported important mutations associated with the outbreak. This study was performed to validate the previous findings and to identify key mutations that had emerged throughout the entire genome of Chikungunya virus that could be driving the enormity of this outbreak. The phylogenetic analysis revealed the closeness of our isolates with ECSA genotype, specifically with the Singapore 2015 strain. We found 2 mutations in C and E2 genes, which were present in our isolates but were non-existent during the period of 2010-2016. Furthermore, re-emergence of Arg amino acid in place of stop codon in nsP3 gene and Thr at E2:312 positions was observed after 2011. We also used computational tools to assess the effect of the identified mutations on the T cell and B cell epitopes that could influence the protective immune response against this infection.


Using the cognitive assessment interview to screen cognitive impairment in psychosis.
Cognitive impairment in psychosis is closely related to functional outcome, so research into psychotic disorders is focusing most effort on treatments for improving cognition. New treatments must show not only an improvement on neuropsychological tests but also in co-primary measures of cognition. The cognitive assessment interview (CAI) is an interview-based measure of cognition which assesses the impact of cognitive deficits in patients' daily lives. Information obtained from patients and their relatives is integrated into a rater composite score. This study examines the validity of the CAI (adapted to Spanish, CAI-Sp) as a screening instrument for cognitive impairment, compared to an objective test of cognitive functioning. The psychometric properties of the CAI-Sp and its association with clinical dimensions are also explored. Eighty-one patients with a psychotic disorder and 38 healthy controls were assessed using the CAI-Sp and the screen for cognitive impairment in psychiatry (SCIP-S). Patients also underwent a clinical assessment. Poorer cognitive functioning as assessed with the CAI-Sp was associated to illness severity, specifically positive, negative and disorganised syndromes. Binary logistic regression showed that the CAI-Sp was able to detect cognitive impairment in patients, when considering CAI-Sp patient and informant information and CAI-Sp rater scores. The CAI-Sp was found to be a valid and reliable scale to assess cognitive functioning in the context of its impact on daily living. Given its ease and speed of application, the CAI-Sp could prove useful in clinical practice, though not a substitute of objective cognitive testing.


Paraneoplastic syndromes.
The importance of paraneoplastic syndromes is often underestimated in the horse. Clinically, paraneoplastic syndromes can cause greater morbidity than the actual physical presence of the malignant tumor. The appearance may be the first sign of a malignancy and may be so severe that appropriate therapy for the underlying cancer is not initiated. This article reviews some of the most common paraneoplastic syndromes that are likely to occur in the horse.


MENTAL HEALTH DISORDERS SUBSEQUENT TO GESTATIONAL DIABETES MELLITUS DIFFER BY RACE/ETHNICITY.
The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. We analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5-6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. Women with compared to women without GDM were older (mean ± standard deviation, 32 ± 5 vs. 30 ± 5 years; P < .001) and had higher body mass index (29.0 ± 7.2 vs. 25.3 ± 5.2 kg/m(2) ; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms.


The effect of a combination of inhaled nitric oxide and an endothelinA-receptor antagonist on hemodynamic dysfunction in experimental acute pulmonary thromboembolism.
Although either inhaled nitric oxide (NO) or endothelinA receptor antagonist has been tried in the treatment of various forms of pulmonary hypertension, the effects of combination therapy have not been reported. We evaluated the effects of inhaled NO alone or a combination of inhaled NO and ZD2574 (an endothelinA receptor antagonist) in an experimental canine acute pulmonary thromboembolism model. Forty parts per million of inhaled NO alone, or a combination of inhaled NO and 10 mg/kg of ZD2574 was administered 1 hour after embolization with an autologous blood clot. We compared the hemodynamic and gas exchange parameters between the two treatment groups. Two treatment regimens decreased mean pulmonary arterial pressure and pulmonary vascular resistance and attenuated decrease in cardiac output. Moreover, systemic arterial hypotension or worsening of hypoxemia did not occur in either of the treatment groups. In the combined group, more favorable hemodynamic outcomes were maintained than in the inhaled NO alone group. And hemodynamic deterioration shown after NO withdrawal was attenuated in the combined group. These findings suggest that when inhaled NO is concomitantly administered with an ETA receptor antagonist, more favorable hemodynamic outcomes can be expected during and after NO inhalation in acute pulmonary thromboembolism.


COVID-19 and children with cancer: Parents' experiences, anxieties and support needs.
Children with cancer were designated as clinically extremely vulnerable if they were to contract SARS-CoV-2 due to immune suppression in the early phase of the COVID-19 pandemic. Our aim was to explore experiences, information and support needs, and decision making of parents with a child with cancer in response to this phase in the United Kingdom. Parents of a child with cancer completed a survey at a time when the UK moved into a period of 'lockdown'. An online survey was developed by the research team to capture parents' experiences, information and support needs, and decision making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken. One hundred seventy-one parents/caregivers completed the survey. Eighty-five percent were worried about the virus and they were vigilant about the virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%), hospital was no longer considered a safe place. Eight overarching themes were identified related to the virus: (a) risk of infection; (b) information, guidance and advice; (c) health care provision; (d) fears and anxieties; or related to lockdown/isolation: (e) psychological and social impact; (f) keeping safe under lockdown; (g) provisions and dependence; and (h) employment and income. This is the first study, to the best of our knowledge, to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The majority of parents were worried about SARS-CoV-2 and transmitting the virus to their child. Hospital was no longer perceived to be a safe place, and parents were worried about suboptimal cancer care. Parents described fear and anxiety and the psychological, social and economic impact of isolation.


A study of educational underachievement in Indian children with epilepsy.
Epilepsy is a chronic disorder that significantly affects learning and behavior. Children with epilepsy are much more vulnerable for educational problems than with any other chronic illness. The study was conducted to assess the extent of educational problems and factors associated with educational underachievement in Indian children with epilepsy. It was a case control study and included 100 cases of 6-16 years age of epilepsy, 50 healthy children (control A) and 50 children with persistent asthma (control B). Their demographic and disease variables were evaluated. The educational performance was assessed by using a predesigned semi structured open ended questionnaire to parents and by teacher's report. Psychological evaluation was done in first step by using a standard questionnaire, childhood psychopathology measurement schedule. In second step, those have shown poor educational performance or significant score in standard questionnaire underwent detailed psychiatric evaluation. Educational problems were reported in cases (36%), control A (2%) and control B (16%). Demographic or disease variables were not associated with educational problems in cases except that boys were more affected than girls. On psychiatric evaluation psychopathological illnesses (47%) like attention deficit hyperkinetic disorder, conduct disorder and depression were found to be commonly associated with poor educational performance (47%) followed by decreased learning opportunities (22.2%) and borderline intelligence (19.4%) in children with epilepsy. Educational problems are commoner in children with epilepsy than with asthma. Psychopathological problems are commonly associated with educational underachievement in children with epilepsy. Therefore periodic psychosocial assessment, counseling and support must be provided to improve the psychosocial adjustment in children with epilepsy.


Recognition of prior learning: its relevance to the proposed unified model of education and training for South African nurses.
Recognition of Prior Learning (R P L) is a fairly new concept in South Africa, and hence different people have different views about R P L. Through this paper, an attempt is made to shed some light on the historical background as well as the philosophical and theoretical underpinnings of R P L. It is hoped that this information will help those nurse educators wishing to experiment with R P L to have a better understanding of how the concept came about. The relevance of R P L to the Unified model of nurse training proposed by the South African Nursing Council is also discussed.


Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors.
We report herein the synthesis, α-glucosidase inhibition and docking studies for a series of 3-15 new flavones. A simple nucleophilic substitution reaction takes place between 3'hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3'hydroxyflavone (2) and the newly synthesized flavones (3-15) were being evaluated for their ability to inhibit activity of α-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 μM as compared to acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 5 (5.45 ± 0.08 μM), 7 (1.26 ± 0.01 μM) and 8 (8.66 ± 0.08 μM) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5-trifluoromethyl-substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by α-glucosidase.


Relationship between melanin-concentrating hormone- and neuropeptide Y-containing neurons in the goldfish hypothalamus.
Intracerebroventricular (ICV) administration of melanin-concentrating hormone (MCH) inhibits food intake in goldfish, unlike the orexigenic action in rodents, via the melanocortin system with suppression of neuropeptide Y (NPY) mRNA expression. We therefore investigated the neuronal relationship between MCH- and NPY-containing neurons in the goldfish brain, using a double-immunofluorescence method and confocal laser scanning microscopy. MCH- and NPY-like immunoreactivities were distributed throughout the brain. In particular, MCH-containing nerve fibers or endings lay in close apposition to NPY-containing neurons in a specific region of the hypothalamus, the nucleus posterioris periventricularis (NPPv). These observations suggest that MCH-containing neurons provide direct input to NPY-containing neurons in the NPPv of goldfish, and that MCH plays a crucial role in the regulation of feeding behavior as an anorexigenic neuropeptide, inhibiting the orexigenic activity of NPY.


Identification of NOG as a specific breast cancer bone metastasis-supporting gene.
Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site, whereas others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provides metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, because it is not enriched in primary tumors with high risk of bone relapse. On the contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression when compared with metastasis to the lung, liver, and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and nonautonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells, it facilitates bone colonization by fostering osteoclast differentiation and bone degradation and also contributes to metastatic lesions reinitiation. These findings reveal how aggressive cancer cell autonomous and nonautonomous functions can be mechanistically coupled to greater bone metastatic potential.


Using a patient prompt list to raise concerns in oncology clinics does not necessarily lead to longer consultations.
Head and neck oncology post-treatment consultations form a critical component of care in terms of support and surveillance. They occur frequently in the first few years and can place substantial demands on healthcare resources. However, they provide useful opportunities for patients to raise issues and receive tailored information and support. The aim of this paper was to assess whether completion of a 56-item patient prompt list (PCI - the Patient Concerns Inventory) immediately prior to the consultation significantly increased its duration. This was a pragmatic cluster preference randomised controlled trial of 288 patients with 15 consultant clusters from two sites "using" (n=8) or "not using" (n=7) the PCI. Consultation times were known for 283 patients (136 PCI, 147 non-PCI) who attended their first post-treatment trial consultation a median (IQR) of 103 (70-160) days after the end of treatment. Consultations lasted a median (IQR) of 10 (7-13) minutes (mean 11) in non-PCI patients and a median (IQR) of 11 (8-15) minutes (mean 12) in PCI patients (p=0.07). After adjustment for patient clustering and significant case mix, the 95% confidence interval for the mean difference was between 1.45minutes shorter with the PCI and 2.98minutes longer (p=0.50). There was significant variation in duration by consultant, tumour stage, treatment mode, overall quality of life (QoL), and distress (all p<0.001). In those who completed the PCI, duration increased with the total number of items selected (p<0.001). In conclusion, the inclusion of a prompt list to help facilitate conversation with patients did not make a substantial difference to consultation times.


Paroxysmal Dyskinesia in Children: from Genes to the Clinic.
Paroxysmal dyskinesia is a genetically and clinically heterogeneous movement disorder. Recent studies have shown that it exhibits both phenotype and genotype overlap with other paroxysmal disorders as well as clinical heterogeneity. We investigated the clinical and genetic characteristics of paroxysmal dyskinesia in children. Fifty-five patients (16 from 14 families and 39 sporadic cases) were enrolled. We classified them into three phenotypes: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). We sequenced PRRT2, SLC2A1, and MR-1 in these patients and reviewed their medical records. Forty patients were categorized as PKD, 14 as PNKD, and 1 as PED. Thirty-eight (69.1%) patients were male, and their age at onset was 8.80±4.53 years (mean±SD). Dystonia was the most common symptom (38 patients, 69.1%). Pathogenic variants were identified in 20 patients (36.4%): 18 with PRRT2 and 2 with SLC2A1. All of the patients with PRRT2 mutations presented with PKD alone. The 2 patients carrying SLC2A1 mutations presented as PNKD and PED, and one of them was treated effectively with a ketogenic diet. Six mutations in PRRT2 (including 2 novel variants) were identified in 9 of the 13 tested families (69.2%) and in 8 patients of the 25 tested sporadic cases (32.0%). There were no significant differences in clinical features or drug response between the PRRT2-positive and PRRT2-negative PKD groups. This study has summarized the clinical and genetic heterogeneity of paroxysmal dyskinesia in children. We suggest that pediatric paroxysmal dyskinesia should not be diagnosed using clinical features alone, but by combining them with broader genetic testing.


Developmental discord among markers for cholinergic differentiation: in vitro time courses for early expression and responses to skeletal muscle extract.
The effects of skeletal muscle extract on the development of CAT, ACh synthesis, high affinity choline uptake, and AChE activities were studied in dissociated ventral spinal cord cultures prepared from 14-day gestational rat embryos. In the absence of muscle extract, the development of CAT and AChE follow biphasic time courses in which they show initial declines followed by periods of steadily increasing activity. In contrast, ACh synthesis and high affinity choline uptake both gradually increase throughout the entire culture period. The presence of muscle extract both prevents the initial decline of CAT and AChE as well as stimulates the rates of development of all four cholinergic markers; however, the degrees and time courses of stimulation differ markedly. The effects of muscle extract on the kinetic and pharmacological properties of ACh synthesis and choline uptake in rat ventral cord cultures were also investigated. Cells treated with muscle extract for 2 days express both high affinity (Km = 1.6 microM) and low affinity (Km = 22 microM) choline uptake mechanisms. Control cells, on the other hand, express only low affinity uptake at this stage but develop a high affinity uptake mechanism by Day 7. During this time both ACh synthesis and high affinity choline uptake become increasingly sensitive to inhibition by hemicholinium-3. These results demonstrate that skeletal muscle factors enhance the development of cholinergic properties in embryonic spinal cord cultures. However, differences in sensitivity to muscle extract concentration, time courses of development, and degrees of stimulation suggest that these changes may involve distinct cellular mechanisms which are differentially affected by skeletal muscle factors.


Tracheomalacia/Tracheobronchomalacia and hyperdynamic airway collapse.
Tracheobronchomalacia (TBM) and hyperdynamic airway collapse (HDAC) can be debilitating diseases associated with decreased functional capacity and poor quality of life, although there is no standard definition of this complex condition, and there are numerous terms used to describe it. The diverse etiology associated with TBM and HDAC can obscure and delay an accurate diagnosis for years. A thorough medical history is important in understanding possible causes and in guiding diagnostic testing. Medical history may also suggest what treatments may be most beneficial.


Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients in Japan indicate that three polymorphic sequences in the tyrosinase gene promoter could be powerful markers for indirect gene diagnosis.
Since 1989, a large number of mutations of the tyrosinase gene, which result in oculocutaneous albinism (OCA), have been reported. However, approximately 15% of patients with tyrosinase-related OCA (OCA1) heterozygously carried an uncharacterized mutation, which presumably existed outside of the ordinarily examined area of the tyrosinase gene. In such cases, polymorphic sequence(s) of the tyrosinase gene might be useful to identify the OCA1 allele. In this study, we examined four polymorphic sequences of the tyrosinase gene in 16 patients with OCA1, their relatives, and 108 normally pigmented Japanese individuals. The results showed a complex dinucleotide repeat in the promoter region at -800 to -900 of seven different lengths, and a polythymidine sequence in the 3' end of intron 2 of three different lengths. Polymerase chain reaction-restriction fragment length polymorphism analysis of two polymorphic sequences at -301 (C/T) and -199 (C/A) in the promoter region allows us to classify the tyrosinase gene into three groups. Using these polymorphic sequences, we could identify the OCA1 allele in more than 80% of cases in which the parents' genomic DNA was available. Three polymorphic sequences in the tyrosinase gene promoter are particularly useful for this purpose.


Ultrastructural and molecular characterization of Glugea serranus n. sp., a microsporidian infecting the blacktail comber, Serranus atricauda (Teleostei: Serranidae), in the Madeira Archipelago (Portugal).
A new microsporidian infecting the connective tissue of the coelomic cavity of the blacktail comber Serranus atricauda, in the Madeira Archipelago (Portugal), is described on the basis of morphological, ultrastructural, and molecular features. The microsporidian formed large whitish xenomas adhering to the peritoneal visceral organs of the host. Each xenoma consisted of a single hypertrophic cell, in the cytoplasm of which mature spores proliferated within parasitophorous vacuoles surrounded by numerous collagen fibers. Mature spores were ellipsoidal and uninucleated, measuring an average of 6.5 ± 0.5 μm in length and 3.4 ± 0.6 μm in width. The anchoring disk of the polar filament was subterminal, laterally shifted from the anterior pole of the spore. The isofilar polar filament coiled in 18-19 turns, forming two rows that surrounded the posterior vacuole. The latter occupied about one third of the spore length. The polaroplast surrounding the apical and uncoiled portion of the polar filament displayed two distinct regions: a lamellar region and an electron-dense globule. Molecular analysis of the rRNA genes, including the internal transcribed spacer region, and phylogenetic analysis using maximum likelihood and neighbor joining demonstrated that this microsporidian parasite clustered with some Glugea species. Based on the differences found both at the morphological and molecular levels, to other members of the genus Glugea, the microsporidian infecting the blacktail comber is considered a new species, thus named Glugea serranus n. sp.


Advanced Human Immunodeficiency Virus Disease at Diagnosis in Mozambique and Swaziland.
Early diagnosis of human immunodeficiency virus (HIV) is a prerequisite to maximizing individual and societal benefits of antiretroviral therapy. Adults ≥18 years of age testing HIV positive at 10 health facilities in Mozambique and Swaziland received point-of-care CD4+ cell count testing immediately after diagnosis. We examined median CD4+ cell count at diagnosis, the proportion diagnosed with advanced HIV disease (CD4+ cell count ≤350 cells/μL) and severe immunosuppression (CD4+ cell count ≤100 cells/μL), and determinants of the latter 2 measures. Among 2333 participants, the median CD4+ cell count at diagnosis was 313 cells/μL (interquartile range, 164-484), more than half (56.5%) had CD4+ ≤350 cells/μL, and 13.9% had CD4+ ≤100 cells/μL. The adjusted relative risk (aRR) of both advanced HIV disease and severe immunosuppression at diagnosis was higher in men versus women (advanced disease aRR = 1.31; 95% confidence interval [CI] = 1.16-1.48; severe immunosuppression aRR = 1.54, 95% CI = 1.17-2.02) and among those who sought HIV testing because they felt ill (advanced disease aRR = 1.30, 95% CI = 1.08-1.55; severe immunosuppression aRR = 2.10, 95% CI = 1.35-2.26). Age 18-24 versus 25-39 was associated with a lower risk of both outcomes (advanced disease aRR = 0.70, 95% CI = 0.59-0.84; severe immunosuppression aRR = 0.62, 95% CI = 0.41-0.95). More than 10 years into the global scale up of comprehensive HIV services, the majority of adults diagnosed with HIV at health facilities in 2 high-prevalence countries presented with advanced disease and 1 in 7 had severe immunosuppression. Innovative strategies for early identification of HIV-positive individuals are urgently needed.


Human fetal brain imaging by magnetoencephalography: verification of fetal brain signals by comparison with fetal brain models.
Fetal magnetoencephalogram (fMEG) is measured in the presence of a large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). This cardiac interference can be successfully removed by orthogonal projection of the corresponding spatial vectors. However, orthogonal projection redistributes the fMEG signal among channels. Such redistribution can be readily accounted for in the forward solution, and the signal topography can also be corrected. To assure that the correction has been done properly, and also to verify that the measured signal originates from within the fetal head, we have modeled the observed fMEG by two extreme models where the fetal head is assumed to be either electrically transparent or isolated from the abdominal tissue. Based on the measured spontaneous, sharp wave, and flash-evoked fMEG signals, we have concluded that the model of the electrically isolated fetal head is more appropriate for fMEG analysis. We show with the help of this model that the redistribution due to projection was properly corrected, and also, that the measured fMEG is consistent with the known position of the fetal head. The modeling provides additional confidence that the measured signals indeed originate from within the fetal head.


Temporal bone borehole accuracy for cochlear implantation influenced by drilling strategy: an in vitro study.
Minimally invasive cochlear implantation is a surgical technique which requires drilling a canal from the mastoid surface toward the basal turn of the cochlea. The choice of an appropriate drilling strategy is hypothesized to have significant influence on the achievable targeting accuracy. Therefore, a method is presented to analyze the contribution of the drilling process and drilling tool to the targeting error isolated from other error sources. The experimental setup to evaluate the borehole accuracy comprises a drill handpiece attached to a linear slide as well as a highly accurate coordinate measuring machine (CMM). Based on the specific requirements of the minimally invasive cochlear access, three drilling strategies, mainly characterized by different drill tools, are derived. The strategies are evaluated by drilling into synthetic temporal bone substitutes containing air-filled cavities to simulate mastoid cells. Deviations from the desired drill trajectories are determined based on measurements using the CMM. Using the experimental setup, a total of 144 holes were drilled for accuracy evaluation. Errors resulting from the drilling process depend on the specific geometry of the tool as well as the angle at which the drill contacts the bone surface. Furthermore, there is a risk of the drill bit deflecting due to synthetic mastoid cells. A single-flute gun drill combined with a pilot drill of the same diameter provided the best results for simulated minimally invasive cochlear implantation, based on an experimental method that may be used for testing further drilling process improvements.


Genetics of idiopathic epilepsies.
One of the most exciting areas in epilepsy has been the explosion in our understanding of the genetics of the epilepsies over the last decade. Built on a long history of careful clinical genetic studies of the epilepsies, the relatively recent discovery of epilepsy genes has enabled insights into pathways causing seizure disorders. A variety of mutational mechanisms can cause epilepsy resulting from different, and sometimes surprising, molecular processes such as copy number variation within the genome. The majority of known epilepsy genes encode ion channel subunits leading many of the genetic epilepsies to be regarded as channelopathies. Understanding how dysfunction of a mutant protein leads to hyperexcitability is key to understanding the pathophysiology of this group of serious and common childhood disorders. The architecture of the common genetic epilepsies following complex inheritance, where multiple genes are involved, is also beginning to be unraveled. The clinical approach to understanding the genetics of the epilepsies has matured and requires a detailed family history of seizures together with delineation of the child's epilepsy syndrome. Recognition of specific genetic epilepsy syndromes enables optimal treatment and prognostic and genetic counseling.


[Immunizing and immunomodulating activity of a wild epidemic parotitis virus at a parotitis infection focus].
The immune status of 18 children previously vaccinated or not with live parotitis vaccine and living in a focus of parotitis was tested over time. Specific antibodies were found in the blood sera or nasal secretion of 88.9% children by follow-up days 10-20, and memory antigen-reactive cells were forming in 55.6%. Functional temporary T-immunodeficiency was observed at the same period in 66.7% children. Although there were no cases of clinically apparent epidemic parotitis, immunologic studies confirmed the circulation of wild type virus. Immunologic studies detected 2 cases of inapparent course of epidemic parotitis.


Treatment of solitary brain metastasis. Resection followed by whole brain radiation therapy (WBRT) and a radiation boost to the metastatic site.
Whole brain radiation therapy (WBRT) is reported to improve local control after resection of brain metastases. Improvement of survival was only observed in patients with controlled extracranial disease. The optimum radiation schedule has yet to be defined. The authors' experience with a postoperative approach including WBRT and a radiation boost to the metastatic site is presented. Criteria for inclusion into this retrospective analysis were solitary brain metastasis, Karnofsky performance status > or = 70%, and controlled extracranial disease. Two therapies were compared for local control and survival: surgery followed by 40 Gy WBRT (group A) versus surgery followed by 40 Gy WBRT and a 10 Gy boost (group B). Statistical analysis was performed using the Kaplan-Meier method and log-rank test. 33 patients were included (17 group A, 16 group B). The results suggested better local control (p = 0.0087) and survival (p = 0.0023) for group B. 17/17 patients (100%) of group A and 13/16 patients (81%) of group B showed progression of brain metastasis, 8/17 and 3/16 patients in the area of metastatic surgery. Median time to progression was 7 (1-22) months in group A and 12 (3-42) months in group B. The number of cancer-related deaths amounted to 17/17 (100%) in group A after a median interval of 9 (3-26) months, and to 9/16 (56%) in group B after 14 (4-46) months. After resection of solitary brain metastasis, a radiation boost in addition to WBRT seems to improve local control and survival when compared to postoperative WBRT alone. The results should be confirmed in a larger prospective trial.


Comparative study on nutrient contents in the different parts of indigenous and hybrid varieties of pumpkin (Cucurbita maxima Linn.).
Two varieties (indigenous and hybrid) of pumpkin (Cucurbita maxima) are cultivated and widely used as food sources in Bangladesh. The aim of this study is to compare nutrient contents in different parts of two varieties of pumpkin. The nutritional compositions were analyzed by standard methods. Fatty acids and amino acids were analyzed by GC/MS and amino acid analyzer. The proximate compositions analysis data indicate that a higher amount of moisture (p < 0.001) and fat (p < 0.01) were observed in the seed of indigenous but the seed of hybrid were rich in crude fiber (p < 0.01) and carbohydrate (p < 0.001). On the contrary carbohydrate content was predominant in the flesh (p < 0.05) and peel (p < 0.01) of indigenous. The energy content was high in the peel, seed and flesh of indigenous (p < 0.001, 0.001 and 0.05 respectively). A significant amount of reducing sugar was found in the peel, flesh (p < 0.05) and seed (p < 0.001) of hybrid. Vitamin C content was high in peel (p < 0.001) and seed (p < 0.01) of indigenous and only in the flesh (p < 0.001) of the hybrid. A remarkable amount of Na, K, Fe and Zn were present in peel (p < 0.001) of hybrid. The notable amount of P and Cu (p < 0.01) were present in the seed and K, Fe and Ca (p < 0.001) were in the flesh of indigenous. The seed of hybrid was enriched with saturated fatty acid (capric acid, p < 0.001; myristic acid, p < 0.01 and stearic acid, p < 0.05), whereas unsaturated fatty acids (oleic, linoleic and linolenic acid, p < 0.05) were rich in the seed of indigenous. A significant amount of threonine, serine, methionine, isoleucine and tyrosine were present in the seed of indigenous (p < 0.01) but only alanine in the seed of hybrid (p < 0.01). These results suggested that a considerable amount of nutrients were present in all three parts of the two varieties, thus both varieties could be the potential source of nutraceuticals.


Altered Degree Centrality of Brain Networks in Parkinson's Disease With Freezing of Gait: A Resting-State Functional MRI Study.
Freezing of gait (FOG) in Parkinson's disease (PD) leads to devastating consequences; however, little is known about its functional brain network. We explored the differences in degree centrality (DC) of functional networks among PD with FOG (PD FOG+), PD without FOG (PD FOG-), and healthy control (HC) groups. In all, 24 PD FOG+, 37 PD FOG-, and 22 HCs were recruited and their resting-state functional magnetic imaging images were acquired. The whole brain network was analyzed using graph theory analysis. DC was compared among groups using the two-sample t-test. The DC values of disrupted brain regions were correlated with the FOG Questionnaire (FOGQ) scores. Receiver operating characteristic curve analysis was performed. We found significant differences in DC among groups. Compared with HCs, PD FOG+ patients showed decreased DC in the middle frontal gyrus (MFG), superior temporal gyrus (STG), parahippocampal gyrus (PhG), inferior temporal gyrus (ITG), and middle temporal gyrus (MTG). Compared with HC, PD FOG- presented with decreased DC in the MFG, STG, PhG, and ITG. Compared with PD FOG-, PD FOG+ showed decreased DC in the MFG and ITG. A negative correlation existed between the DC of ITG and FOGQ scores; the DC in ITG could distinguish PD FOG+ from PD FOG- and HC. The calculated AUCs were 81.3, 89.5, and 77.7% for PD FOG+ vs. HC, PD FOG- vs. HC, and PD FOG+ vs. PD FOG-, respectively. In conclusion, decreased DC of ITG in PD FOG+ patients compared to PD FOG- patients and HCs may be a unique feature for PD FOG+ and can likely distinguish PD FOG+ from PD FOG- and HC groups.


Environmentally friendly method to grow wide-bandgap semiconductor aluminum nitride crystals: Elementary source vapor phase epitaxy.
Aluminum nitride (AlN) has attracted increasing interest as an optoelectronic material in the deep ultraviolet spectral range due to its wide bandgap of 6.0 eV (207 nm wavelength) at room temperature. Because AlN bulk single crystals are ideal device substrates for such applications, the crystal growth of bulky AlN has been extensively studied. Two growth methods seem especially promising: hydride vapor phase epitaxy (HVPE) and sublimation. However, the former requires hazardous gases such as hydrochloric acid and ammonia, while the latter needs extremely high growth temperatures around 2000 °C. Herein we propose a novel vapor-phase-epitaxy-based growth method for AlN that does not use toxic materials; the source precursors are elementary aluminum and nitrogen gas. To prepare our AlN, we constructed a new growth apparatus, which realizes growth of AlN single crystals at a rate of ~18 μm/h at 1550 °C using argon as the source transfer via the simple reaction Al + 1/2N2 → AlN. This growth rate is comparable to that by HVPE, and the growth temperature is much lower than that in sublimation. Thus, this study opens up a novel route to achieve environmentally friendly growth of AlN.


Screening for substance use disorders in neurodevelopmental disorders: a clinical routine?
Evidence suggests that substance use disorders (SUD) tend to be underdiagnosed in psychiatry. The objective of this study was to investigate whether drug and alcohol screening is a clinical routine in the assessment of two prominent neurodevelopmental disorders, namely ADHD and autism spectrum disorder (ASD). We surveyed drug and alcohol screening routines in 34 general child and adolescent (only practice for adolescents, not children, was assessed) and 29 adult psychiatric outpatient departments in Stockholm County, Sweden. Structured telephone interviews mapping SUD screening procedures were conducted with department representatives in charge. Only a minority of child and adolescent departments regularly used SUD screening questionnaires (6 %) in ADHD and ASD assessment, while this was more common in adult psychiatry (55 %). Urine/blood-based toxicology tests were always used in 28 % and sometimes or in case of clinical suspicion in 38 % of the adult units. Such tests were used sometimes or in case of clinical suspicion in 15 % of the child psychiatric departments, but never routinely. Findings reveal that screening for SUD in ADHD and ASD is not an integral part of routine clinical assessments in psychiatry, although increasingly an integral part of many clinical guidelines. Thus, SUD might be underdiagnosed in neurodevelopmental disorders, which could be particularly true for child and adolescent psychiatry settings.


Visual Quality, Motility Behavior, and Retinal Changes Associated with Reading Tasks Performed on Electronic Devices.
The purpose of this study was to objectively evaluate visual discomfort using an eye tracker and aberrometer after a 21-min reading session on an iPad and an Ebook. Additionally, retinal changes were analyzed using optical coherence tomography (OCT). A total of 31 young subjects (24 ± 4 years) participated in this study. They read for 21 min on an Ebook and for another 21 min on an iPad under controlled lighting conditions while their eye movements were monitored using an eye tracker. Aberrometry and retinal OCT measurements were taken before and after each reading session. Parameters such as pupil diameter, fixations, saccades, blinks, total aberration, high-order aberration, low-order aberration, and central and peripheral retinal thickness in the nine early treatment diabetic retinopathy study (ETDRS) areas were measured for each reading situation. Statistical analysis was performed on the collected data. No statistically significant differences (p > 0.05) between the two devices were observed in terms of the different types of eye movements or the changes in retinal thickness. However, the aberrometric analysis showed variations in post-reading situations depending on the device used. Reading speed and visual discomfort resulting from electronic device usage can be objectively assessed using an eye tracker and aberrometer. Additionally, changes found in central and peripheral retinal thickness between the two devices and the baseline measurements were not significant and remained relatively stable.


Zero absolute vorticity: insight from experiments in rotating laminar plane Couette flow.
For pressure-driven turbulent channel flows undergoing spanwise system rotation, it has been observed that the absolute vorticity, i.e., the sum of the averaged spanwise flow vorticity and system rotation, tends to zero in the central region of the channel. This observation has so far eluded a convincing theoretical explanation, despite experimental and numerical evidence reported in the literature. Here we show experimentally that three-dimensional laminar structures in plane Couette flow, which appear under anticyclonic system rotation, give the same effect, namely, that the absolute vorticity tends to zero if the rotation rate is high enough. It is shown that this is equivalent to a local Richardson number of approximately zero, which would indicate a stable condition. We also offer an explanation based on Kelvin's circulation theorem to demonstrate that the absolute vorticity should remain constant and approximately equal to zero in the central region of the channel when going from the nonrotating fully turbulent state to any state with sufficiently high rotation.


Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels.
To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels.


Cation transport in oxidant-stressed human erythrocytes: heightened N-ethylmaleimide activation of passive K+ influx after mild peroxidation.
Normal and chronically dehydrated (hereditary xerocytosis) human red cells were subjected to mild peroxidative treatment (315 microM hydrogen peroxide (H2O2), 15 min) in the presence of azide. The subsequent expression of passive (ouabain-resistant) K+ transport activities was analyzed by measurement of 86Rb+ influx. Peroxidation of normal red cells did not affect basal K+ transport activity, but the increment in K+ influx elicited by 0.5 mM N-ethylmaleimide (NEM) was increased 3-fold. The enhanced K+ influx was chloride-dependent, but only partially inhibited by 0.1 mM furosemide. Stimulated activity declined progressively after NEM activation, but could be restored by a second NEM treatment. Prior conversion of hemoglobin to the carbonmonoxy form abolished the response to peroxide, while 200 microM butylated hydroxytoluene (BHT) exerted only partial inhibition, suggesting that the effect of H2O2 requires interaction of activated, unstable hemoglobin species with the membrane, but that lipid peroxidation is not sufficient. Peroxidation following NEM treatment also enhanced NEM activation, indicating that enhancement does not require altered NEM reactions with stimulatory or inhibitory sites. Passive K+ transport in hereditary xerocytosis red cells was not activated by NEM, with or without H2O2 pretreatment. The results demonstrate that modest peroxidative damage to red cells can heighten the activation of a transport system that is thought to be capable of mediating net K+ efflux and volume reduction in cells that express it. Models are proposed in which the effects of NEM, H2O2, cell swelling and other factors are mediated by conformational changes in a postulated subpopulation of anion channel (Band 3) molecules that bind the K+ transporter.


Candidate microbicides and their mechanisms of action.
The development of prevention strategies against sexual transmission of human immunodeficiency-1 virus (HIV-1) is essential to curb the rate of new infections. New prevention options include microbicides, many of which are based on antiretroviral (ARV) drugs targeting different stages of the viral replication cycle including: viral entry and fusion; reverse transcription; integration; and viral maturation through proteolytic clevage. In this review, we discuss current and new potential candidate microbicides designed to prevent mucosal HIV acquisition. Preclinical methods, including cellular, tissular, and animal models, used to assess candidate microbicides and evaluate their prioritization for progress through the product development pipeline are reviewed in context with a rapidly evolving clinical landscape.


Titanium Elastic Nail versus plate fixation of displaced midshaft clavicle fractures: A retrospective comparison study.
This study has two purposes: (1) to compare the clinical results between the Titanium Elastic Nail (TEN) and plate fixation of the displaced midshaft clavicle fracture; and (2) to demonstrate the relationship between length shortening and functional outcome after TEN fixation, especially in the comminuted fracture pattern. A retrospective, case-controlled study was conducted and 55 patients were included in our study: 25 in the TEN fixation group (TEN group) and 30 in the plate fixation group (plate group). All patients were classified into four subgroups: simple fracture in the TEN group (ST; n = 13), simple fracture in the plate group (SP; n = 15), comminuted fracture in the TEN group (CT; n = 12), and comminuted fracture in the plate group (CP; n = 15). Wound size was significantly smaller in the TEN group (p < 0.001). The injured clavicular length after fracture healing was significantly shorter in the TEN group (p = 0.036). There was no significant difference in the mean Constant and DASH scores. Injured clavicle shortening was significantly larger in the CT subgroup (p = 0.018). However, there was no statistically significant difference in Constant score and DASH score while comparing the CT subgroup to other subgroups. Although TEN fixation may lead to a higher degree of length shortening after bony union especially in cases of comminuted fracture pattern, no statistically significant difference was observed in objective functional results as compared to other subgroups. Therefore, TEN can be used to fix a displaced midshaft clavicle fracture even in cases of comminuted fracture pattern, which overall is an effective and less surgically invasive procedure.


Error processing in current and former cocaine users.
Deficits in response inhibition and error processing can result in maladaptive behavior, including failure to use past mistakes to inform present decisions. A specific deficit in inhibiting a prepotent response represents one aspect of impulsivity and is a prominent feature of addictive behaviors in general, including cocaine abuse/dependence. Brain regions implicated in cognitive control exhibit reduced activation in cocaine abusers. The purposes of the present investigation were (1) to identify neural differences associated with error processing in current and former cocaine-dependent individuals compared to healthy controls and (2) to determine whether former, long-term abstinent cocaine users showed similar differences compared with current users. The present study used an fMRI Go/No-Go task to investigate differences in BOLD response to correct rejections and false alarms between current cocaine users (n = 30), former cocaine users (n = 29), and healthy controls (n = 35). Impulsivity trait measures were also assessed and compared with BOLD activity. Nineteen regions of interest previously implicated in errors of disinhibition were queried. There were no group differences in the correct rejections condition, but both current and former users exhibited increased BOLD response relative to controls for false alarms. In current users, the pregenual cingulate gyrus and left angular/supramarginal gyri overactivated. In former users, the right middle frontal/precentral gyri, right inferior parietal lobule, and left angular/supramarginal gyri overactivated. Overall, our results support a hypothesis that neural activity in former users differs more from healthy controls than that of current users due to cognitive compensation that facilitates abstinence.


Age Is Just a Number: WPATH-Affiliated Surgeons' Experiences and Attitudes Toward Vaginoplasty in Transgender Females Under 18 Years of Age in the United States.
A rising number of female-affirmed transgender adolescents are being treated with gonadotropin-releasing hormone analogues and subsequently cross-sex hormones at early or mid-puberty, with vaginoplasty as the presumed final step in their physical transition. But, despite the minimum age of 18 years defining eligibility to undergo this irreversible procedure, anecdotal reports have shown that vaginoplasties are being performed on minors by surgeons in the United States, thereby contravening the World Professional Association for Transgender Health (WPATH) standards of care (SOC). To explore surgeons' attitudes toward ethical guidelines in the SOC; any professional experiences of performing vaginoplasty on transgender minors; views of surgical risks, benefits, and harm reduction measures; and perceptions of future challenges and concerns in this area of surgical practice. A qualitative semistructured interview approach was used to collect data from 13 male and 7 female surgeons who perform transgender vaginoplasty in the United States. Professional experiences and attitudes toward vaginoplasty in transgender minors were analyzed using the constant comparative method applied to 20 individual interview transcripts. While there was close agreement concerning surgical techniques, proper patient selection, and predictive elements of postoperative success, attitudes toward the SOC and the reliance on the guidelines varied. The sole practitioner model is gradually giving way to a more holistic team approach, with patient responsibility dispersed among different professionals. Different approaches to surgical training, professional standards, and fellowship programs were suggested. Several participants expressed a need for centralized data collection, patient tracking, and increased involvement of the WPATH as a sponsor of studies in this emergent population. Drawing on surgeons' attitudes and experiences is essential for the development of standards and practices. A more precise and transparent view of this surgical procedure will be essential in contributing to the updated version 8 of the WPATH SOC. The abundant data elicited from the interviews address several meaningful research questions, most importantly patient selection criteria, surgical methods, and issues critical to the future of the profession. Nevertheless, the limited sample might not be representative of the surgical cadre at large, particularly when exploring experiences and attitudes toward vaginoplasty in minors. A larger participant pool representing WPATH-affiliated surgeons outside the United States would improve the generalizability of the study. Taken together, the study and its findings make a significant contribution to the planned revision of the WPATH SOC. Milrod C, Karasic DH. Age Is Just a Number: WPATH-Affiliated Surgeons' Experiences and Attitudes Toward Vaginoplasty in Transgender Females Under 18 Years of Age in the United States. J Sex Med 2017;14:624-634.


Artificial visual perception neural system using a solution-processable MoS2-based in-memory light sensor.
Optoelectronic devices are advantageous in in-memory light sensing for visual information processing, recognition, and storage in an energy-efficient manner. Recently, in-memory light sensors have been proposed to improve the energy, area, and time efficiencies of neuromorphic computing systems. This study is primarily focused on the development of a single sensing-storage-processing node based on a two-terminal solution-processable MoS2 metal-oxide-semiconductor (MOS) charge-trapping memory structure-the basic structure for charge-coupled devices (CCD)-and showing its suitability for in-memory light sensing and artificial visual perception. The memory window of the device increased from 2.8 V to more than 6 V when the device was irradiated with optical lights of different wavelengths during the program operation. Furthermore, the charge retention capability of the device at a high temperature (100 °C) was enhanced from 36 to 64% when exposed to a light wavelength of 400 nm. The larger shift in the threshold voltage with an increasing operating voltage confirmed that more charges were trapped at the Al2O3/MoS2 interface and in the MoS2 layer. A small convolutional neural network was proposed to measure the optical sensing and electrical programming abilities of the device. The array simulation received optical images transmitted using a blue light wavelength and performed inference computation to process and recognize the images with 91% accuracy. This study is a significant step toward the development of optoelectronic MOS memory devices for neuromorphic visual perception, adaptive parallel processing networks for in-memory light sensing, and smart CCD cameras with artificial visual perception capabilities.


Following 4 months of social distancing during COVID-19 Pandemic in Brazil did not change aspects of functioning in children and adolescents with developmental disabilities: A longitudinal study.
The COVID-19 pandemic and its demands of social distancing have created challenges in the lives of children/adolescents with developmental disabilities and their families, which would change aspects of children's functioning. The objetive of this study was to evaluate changes in some components of functioning of children/adolescents with disabilities following 4 months of social distancing during a period of high contamination rate in the year 2020 in Brazil. Participated 81 mothers of children/adolescents with disabilities, 3-17 years, most of them (80%) diagnosed with Down syndrome, cerebral palsy and autism spectrum disorder. Remote assessments of functioning' aspects including IPAQ, YC-PEM/ PEM-C, Social Support Scale and PedsQL V.4.0. Wilcoxon tests compared the measures, with significance level <0.05. No significant changes in participant's functioning were identified. Social adjustments required to facing the pandemic during two points in time in the midst of the pandemic did not change the evaluated aspects of functioning in our sample of Brazilian.


Anti-inflammatory effects of the chinese herbal formula sini tang in myocardial infarction rats.
The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor- α , interleukin-6, and interleukin-1 β (TNF- α , IL-6, and IL-1 β ) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF- α , IL-6, and IL-1 β in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses.


Gender differences revealed in the right posterior temporal areas during Navon letter identification tasks.
Gender differences in temporo-spectral EEG patterns during verbal cognitive performance are poorly understood. The aim of the present study was to examine whether the event-related dynamics of EEG differ between genders during the performance of Navon letter identification tasks (NLITs). To this end, the EEG patterns of 40 subjects were recorded during the NLIT performance. We compared behavioral outcomes, event-related temporo-spectral dynamics, and source distribution of neural oscillations within cortical regions of male and female subjects. We found that male subjects exhibited greater induced neural activities than female subjects in right temporo-parietal areas at theta and alpha frequency bands. Source imaging for the time ranges at which maximal gender differences were observed revealed gender-dependent estimated current densities in the right posterior temporal regions. These gender differences can be explained by the existence of distinct, gender-specific hemispheric specialization. Thus, gender differences should be considered during behavioral tasks and electrophysiological measurements.


The curious cases of tetrahydrosalen-type ligands interacting with Ni(II): structures and ligand-based oxidation reactions.
This work centers around the nickel complexes derived from two tetrahydrosalen-type proligands: N,N'-bis(2-hydroxybenzyl)-o-phenylenediamine (H2salophan) and N,N'-bis(2-hydroxy-3-methylbenzyl)-o-phenylenediamine (H2salophan_Me). The reaction of H2salophan with Ni(OAc)2·4H2O generates a dinuclear complex Ni2(Hsalophan)2(OAc)2 or Na[Ni2(salophan)2(OAc)] when NaOH is added to assist ligand deprotonation. The reaction of H2salophan_Me with Ni(OAc)2·4H2O, however, yields a mononuclear complex Ni(Hsalophan_Me)2. Unlike the corresponding salen-type nickel complexes, these tetrahydrosalen-type complexes are paramagentic and air sensitive (in solution). Oxidation by O2 or peroxides results in dehydrogenation of the ligand backbone to form the salen-type complexes.


Comparison of short- (one month) and long- (twelve months) term outcomes of sirolimus- versus paclitaxel-eluting stents in 293 consecutive patients with diabetes mellitus (from the RESEARCH and T-SEARCH registries).
This study evaluated and compared the efficacy of sirolimus-eluting stents (n = 145 patients) with that of paclitaxel-eluting stents (n = 148 patients) in 293 consecutive unselected patients who had diabetes mellitus. Baseline clinical characteristics and presentations were similar: mean age of 64 years, 50% presented with unstable angina or myocardial infarction, and 66% had multivessel disease. Angiographic and procedural characteristics differed, with more complex lesions and more vein grafts managed in the paclitaxel-eluting stent group. Overall mean stented length was 46 +/- 32 mm. There were no differences in unadjusted outcomes by stent type (1-year major adverse cardiac event rates of 20.4% for sirolimus-eluting stents vs 15.6% for paclitaxel-eluting stents, p = 0.12) or when adjusted for multivariate predictors (adjusted hazard ratio 0.68, 95% confidence interval 0.37 to 1.24, p = 0.21). Independent predictors of outcome in patients who had diabetes mellitus were stenting of the left main artery, stenting of the left anterior descending artery, creatinine clearance, and female gender. Patients who required insulin had a significantly higher, crude major adverse cardiac event rate at 1 year compared with those who used oral agents, but this rate became nonsignificant when adjusted for independent predictors of outcome.


CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis.
Cyclin-dependent kinases (CDKs) restrict DNA replication origin firing to once per cell cycle by preventing the assembly of prereplicative complexes (pre-RCs; licensing) outside of G1 phase. Paradoxically, under certain circumstances, CDKs such as cyclin E-cdk2 are also required to promote licensing. Here, we show that CDK phosphorylation of the essential licensing factor Cdc6 stabilizes it by preventing its association with the anaphase promoting complex/cyclosome (APC/C). APC/C-dependent Cdc6 proteolysis prevents pre-RC assembly in quiescent cells and, when cells reenter the cell cycle from quiescence, CDK-dependent Cdc6 stabilization allows Cdc6 to accumulate before the licensing inhibitors geminin and cyclin A which are also APC/C substrates. This novel mechanism for regulating protein stability establishes a window of time prior to S phase when pre-RCs can assemble which we propose represents a critical function of cyclin E.