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Summary: Camel milk and its products are gaining higher demand due to their attractive nutritional and therapeutic profile. However, manufacturing of camel milk cheese (CMC) is a challenging task. This study aimed to compare the quality of camel milk cheese made using different starter cultures. Four groups CM (camel milk + mesophilic cultures), CT (camel milk + thermophilic cultures), CBM (camel milk + 10% buffalo milk using mesophilic cultures), and CBT (camel milk + 10% buffalo milk using thermophilic cultures) were created. The cheeses were stored for 60 days at 4 °C to assess their physicochemical, sensory, and proteolytic properties. Results indicated highest moisture content in CM (70.19%) as opposed to the lowest moisture in CBT (55.19%). In addition, CM and CBM revealed lower acidity (0.63% and 0.66%) in contrast with CT and CBT (0.78% and 0.83%, respectively). On the other hand, CBM and CBT exhibited higher contents of protein (21.04, 21.57%) and fat (17.65, 17.70%) during storage. All quality indices of cheese samples significantly declined (P < 0.01) during storage excluding acidity. Sensory analyses revealed that panellists highly preferred CBT treatment followed by CBM and CT. Furthermore, urea‐PAGE and RP‐HPLC were performed for the proteolytic study of cheese samples. The study revealed that the presence of buffalo milk and thermophilic cultures in cheese resulted in a decrease concentration of intact caseins (αs1, β‐, and κ‐caseins) as storage days passed. The degree of proteolysis was found to be higher in CBT compared to CBM, CT, and CM. Based on the results, it was concluded that the use of pasteurisation at 65 °C for 30 min, pH of 5.5, 0.06% CaCl2, and the incorporation of 10% buffalo milk using thermophilic cultures (Lactobaccilus bulgaricus and Streptococcus thermophilus) resulted in desirable quality characteristics. [ABSTRACT FROM AUTHOR]

Background and purpose: Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men. Methods: Using the large well‐defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open‐label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex‐ and age‐related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35–44, ≥45 years). Exact p‐values are given for this exploratory analysis. Results: Frequencies of mono‐ versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35–44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35–44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only. Conclusions: We describe sex‐specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations. [ABSTRACT FROM AUTHOR]

Rationale: 4,7‐Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high‐resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI‐MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. Methods: Five DCQ derivatives were synthesized by using previously described protocols. ESI‐MS/MS analyses were carried out with a quadrupole/time‐of‐flight and ion‐trap instrument. The proposed gas‐phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. Results: DCQ bromides or aldehydes (C‐3 or C‐8 positions), as well as the trimethylsilyl derivative (C‐3 position), were prepared. Detailed ESI‐MS/MS data revealed heteroatom elimination through an exception to the even‐electron rule, to originate open‐shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. Conclusion: Our results provided a well‐founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti. [ABSTRACT FROM AUTHOR]

Kam Sweet Rice is a high-quality local variety of Guizhou province in China, but most varieties have awns on lemma. In this study, we aimed to obtain awnless varieties of Kam Sweet Rice by blocking the awn development-related gene OsGAD1 using CRISPR/Cas9 technology. We determined that natural variations of the OsGAD1 triggered different lengths of awns of Kam Sweet Rice. We found that the awning rate of the CRISPR lines of OsGAD1 in Guxiangnuo, Goujingao and Gouhuanggang decreased by over 65%, and the number of grains per panicle and yield per plant increased by more than 17% and 20% compared to the wild-types. Furthermore, we indicated that blocking OsGAD1 resulted in an increase of over 2% in the brown rice rate and milled rice rate in these varieties. In addition, the analysis of the transcriptome revealed that the regulation of awn development and yield formation in CRISPR lines of OsGAD1 may involve genes associated with phytohormone and nitrogen pathways. These results suggest that blocking OsGAD1 in Kam Sweet Rice using CRISPR/Cas9 technology can be used for breeding programs seeking high yield and grain quality of Kam Sweet Rice. [ABSTRACT FROM AUTHOR]

Aims: Treatment of multiple sclerosis (MS) relapses consists of short‐term administration of high‐dose glucocorticoids (GCs). However, over 40% of patients show an insufficient response to GC treatment. We aimed to develop a predictive model for such GC resistance. Methods: We performed a receiver operating characteristic (ROC) curve analysis following the transcriptomic assay of whole blood samples from stable, relapsing GC‐sensitive and relapsing GC‐resistant patients with MS in two different European centers. Results: We identified 12 genes being regulated during a relapse and differentially expressed between GC‐sensitive and GC‐resistant patients with MS. Using these genes, we defined a statistical model to predict GC resistance with an area under the curve (AUC) of the ROC analysis of 0.913. Furthermore, we observed that relapsing GC‐resistant patients with MS have decreased GR, DUSP1, and TSC22D3 mRNA levels compared with relapsing GC‐sensitive patients with MS. Finally, we showed that the transcriptome of relapsing GC‐resistant patients with MS resembles those of stable patients with MS. Conclusion: Predicting GC resistance would allow patients to benefit from prompt initiation of an alternative relapse treatment leading to increased treatment efficacy. Thus, we think our model could contribute to reducing disability development in people with MS. [ABSTRACT FROM AUTHOR]

Background and purpose: Kelchlike protein 11 antibodies (KLHL11‐IgGs) were first described in 2019 as a marker of paraneoplastic neurological syndromes (PNSs). They have mostly been associated with testicular germ cell tumors (tGCTs). Methods: Two patients with KLHL11‐IgG encephalitis are reported, and the literature is comprehensively reviewed. Results: Patient 1 had been in remission from a tGCT 10 years prior. He developed episodic vertigo and diplopia progressing over a few days. Treatment with corticosteroids (CSs) was started a few days after symptom onset. Patient 2 had transient diplopia, which resolved spontaneously. Visual problems persisted for 7 months, when he additionally developed a progressive cerebellar syndrome. One year after onset, CS treatment was started. Initial magnetic resonance imaging was unremarkable in both patients, but analysis of cerebrospinal fluid (CSF) revealed chronic inflammation. KLHL11‐IgG was positive in both patients (Patient 1 only in CSF, Patient 2 in serum). Neoplastic screening has so far not revealed any signs of active underlying malignancy. We found 15 publications of 112 patients in total with KLHL11‐IgG encephalitis. Most patients (n = 82) had a cerebellar syndrome with or without signs of rhombencephalitis. The most common symptoms were ataxia (n = 82) and vertigo (n = 47), followed by oculomotor disturbances (n = 35) and hearing disorders (n = 31). Eighty of 84 patients had a GCT as an underlying tumor. Conclusions: Our cases demonstrate classical symptoms of KLHL11‐IgG encephalitis. Early diagnosis and therapy are imperative. As with other PNSs, clinical awareness is needed and further studies are required especially in regard to therapeutic management. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine challenges, competencies, and supportive care needs (SCN) of women with breast or gynecological cancer during acute cancer treatment and associations to other health‐related variables. Methods: We surveyed 120 patients with breast or gynecological cancer at the end of acute cancer treatment, either directly after surgery or during adjuvant chemotherapy. We assessed challenges, subjective competencies, and SCN using a self‐developed measure comprising 25 items referring to coping tasks assigned to six domains. In addition, patients' competencies and health literacy (HL) were assessed. Results: Most patients felt at least moderately challenged by coping tasks concerning psychological distress (e.g., dealing with fears and insecurities, 70.2%; coping with cancer diagnosis, 69.6%) and physical complaints (e.g., dealing with a reduced physical capacity, 56.6%). About 42.5%–71.4% of patients who evaluated coping tasks as highly challenging felt competent to deal with these challenges themselves. Less than half of patients reported SCN, mainly regarding psychological concerns. The extent of challenging coping tasks, patients' perceived ability to overcome challenges themselves, and SCN showed associations to patient competencies and HL. Conclusions: SCN regarding psychological concerns and health behavior should be addressed in acute cancer care and rehabilitation programs. In addition, promoting HL might be essential in strengthening patients' subjective competencies related to various coping tasks. [ABSTRACT FROM AUTHOR]

Background and purpose: Neuronal autoantibodies can support the diagnosis of primary autoimmune cerebellar ataxia (PACA). Knowledge of PACA is still sparce. This article aims to highlight the relevance of anti‐neurochondrin antibodies and possible therapeutical consequences in people with PACA. Methods: This is a case presentation and literature review of PACA associated with anti‐neurochondrin antibodies. Results: A 33‐year‐old man noticed reduced control of the right leg in May 2020. During his first clinic appointment at our institution in September 2021, he complained about gait imbalance, fine motor disorders, tremor, intermittent diplopia and slurred speech. He presented a pancerebellar syndrome with stance, gait and limb ataxia, scanning speech and oculomotor dysfunction. Within 3 months the symptoms progressed. An initial cerebral magnetic resonance imaging, June 2020, was normal, but follow‐up imaging in October 2021 and July 2022 revealed marked cerebellar atrophy (29% volume loss). Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 11 x 103/L (normal range 0–4) and oligoclonal bands type II. Anti‐neurochondrin antibodies (immunoglobulin G) were detected in serum (1:10,000) and cerebrospinal fluid (1:320, by cell‐based indirect immunofluorescence assay and immunoblot, analysed by the EUROIMMUN laboratory). After ruling out alternative causes and neoplasia, diagnosis of PACA was given and immunotherapy (steroids and cyclophosphamide) was started in January 2022. In March 2022 a stabilization of disease was observed. Conclusion: Cerebellar ataxia associated with anti‐neurochondrin antibodies has only been described in 19 cases; however, the number of unrecognized PACAs may be higher. As anti‐neurochondrin antibodies target an intracellular antigen and exhibit a mainly cytotoxic T‐cell‐mediated pathogenesis, important therapeutic implications may result. Because of the severe and rapid clinical progression, aggressive immunotherapy was warranted. This case highlights the need for rapid diagnosis and therapy in PACA, as stabilization and even improvement of symptoms are attainable. [ABSTRACT FROM AUTHOR]

Brain morphometry is usually based on non‐enhanced (pre‐contrast) T1‐weighted MRI. However, such dedicated protocols are sometimes missing in clinical examinations. Instead, an image with a contrast agent is often available. Existing tools such as FreeSurfer yield unreliable results when applied to contrast‐enhanced (CE) images. Consequently, these acquisitions are excluded from retrospective morphometry studies, which reduces the sample size. We hypothesize that deep learning (DL)‐based morphometry methods can extract morphometric measures also from contrast‐enhanced MRI. We have extended DL+DiReCT to cope with contrast‐enhanced MRI. Training data for our DL‐based model were enriched with non‐enhanced and CE image pairs from the same session. The segmentations were derived with FreeSurfer from the non‐enhanced image and used as ground truth for the coregistered CE image. A longitudinal dataset of patients with multiple sclerosis (MS), comprising relapsing remitting (RRMS) and primary progressive (PPMS) subgroups, was used for the evaluation. Global and regional cortical thickness derived from non‐enhanced and CE images were contrasted to results from FreeSurfer. Correlation coefficients of global mean cortical thickness between non‐enhanced and CE images were significantly larger with DL+DiReCT (r = 0.92) than with FreeSurfer (r = 0.75). When comparing the longitudinal atrophy rates between the two MS subgroups, the effect sizes between PPMS and RRMS were higher with DL+DiReCT both for non‐enhanced (d = −0.304) and CE images (d = −0.169) than for FreeSurfer (non‐enhanced d = −0.111, CE d = 0.085). In conclusion, brain morphometry can be derived reliably from contrast‐enhanced MRI using DL‐based morphometry tools, making additional cases available for analysis and potential future diagnostic morphometry tools. [ABSTRACT FROM AUTHOR]

Images of sexualized women depicted as animals or alongside meat are routinely used in advertising in Western culture. Philosophers and feminist scholars have long theorized that such imagery reflects the lower status of both women and animals (vs. men) in society and argued that prejudiced attitudes towards women (i.e., sexism) and animals (i.e., speciesism) are interconnected, with meat‐eating as a core symbol of masculinity. Addressing these key ideas from ecofeminist theory, we review the psychological evidence on the associations between sexism, speciesism, meat, and masculinity. Research on the animalistic dehumanization of women provides evidence that sexism and speciesism are psychologically entangled and rooted in desires for group‐based dominance and inequality. Furthermore, research on the symbolic value of meat corroborates its masculine value expressing dominance and power, and suggests that men who abstain from meat consumption (e.g., vegans) are feminized and devalued, particularly by those higher in sexism. We conclude that a greater recognition of the interconnected nature of patriarchal gender relations and practices of animal exploitation, including meat‐eating, can help in efforts to improve the status of both women and animals. [ABSTRACT FROM AUTHOR]

Introduction: Data on structural brain changes after infection with SARS‐CoV‐2 is sparse. We postulate multiple sclerosis as a model to study the effects of SARS‐CoV‐2 on brain atrophy due to the unique availability of longitudinal imaging data in this patient group, enabling assessment of intraindividual brain atrophy rates. Methods: Global and regional cortical gray matter volumes were derived from structural MRIs using FreeSurfer. A linear model was fitted to the measures of the matching pre‐SARS‐CoV‐2 images with age as an explanatory variable. The residuals were used to determine whether the post‐SARS‐CoV‐2 volumes differed significantly from the baseline. Results: Fourteen RRMS patients with a total of 113 longitudinal magnetic resonance images were retrospectively analyzed. We found no acceleration of brain atrophy after infection with SARS‐CoV‐2 for global gray matter volume (p = 0.17). However, on the regional level, parahippocampal gyri showed a tendency toward volume reduction (p = 0.0076), suggesting accelerated atrophy during or after infection. Conclusions: Our results illustrate the opportunity of using longitudinal MRIs from existing MS registries to study brain changes associated with SARS‐CoV‐2 infections. We would like to address the global MS community with a call for action to use the available cohorts, reproduce the proposed analysis, and pool the results. [ABSTRACT FROM AUTHOR]

Youth in conflict‐affected regions are exposed to a multitude of traumatic events. These individuals often witness violence; experience it firsthand; and, in some cases, become perpetrators. The interplay of events shapes systematic trauma histories that may have unique implications for youths' mental health. In a cross‐sectional study conducted in eastern Democratic Republic of Congo (DRC), we interviewed 295 war‐affected youth (63.4% boys, Mage = 16.70 years), including former child soldiers (n = 171), regarding their traumatic experiences and mental health. Using latent class analysis, we identified four common trauma history classes categorized by (a) low exposure, (b) medium exposure, (c) high exposure, and (d) high exposure/perpetration. Across the sample, gradual increases in trauma load corresponded with increased vulnerability to posttraumatic stress disorder (PTSD) symptoms, ηp2 =.36, and internalizing problems, ηp2 =.12; however, only youth from the high exposure/perpetration class differed significantly from other youth in their levels of externalizing problems, ηp2 =.13, and offending behaviors, ηp2 =.17. A longer time in armed groups was related to a higher risk of both experiencing and perpetrating violence. The results indicate that it is not child soldier status, per se, but the perpetration of violence that reinforces a cycle of violence in conflict‐affected societies by contributing to increased externalizing problems and offending behaviors. In conflict regions, integrated approaches are needed to address both trauma and externalizing problems of war‐affected youth. [ABSTRACT FROM AUTHOR]

Introduction: Post‐COVID‐19 syndrome affects approximately 10–25% of people after a COVID‐19 infection, irrespective of initial COVID‐19 severity. The aim of this project was to assess the clinical characteristics, course, and prognosis of post‐COVID‐19 syndrome using a systematic multidimensional approach. Patients and Methods: An online survey of people with suspected and confirmed COVID‐19 and post‐COVID‐19 syndrome, distributed via Swiss COVID‐19 support groups, social media, and our post‐COVID‐19 consultation, was performed. A total of 8 post‐infectious domains were assessed with 120 questions. Data were collected from October 15 to December 12, 2021, and 309 participants were included. Analysis of clinical phenomenology of post‐COVID‐19 syndrome was performed using comparative statistics. Results: The three most prevalent post‐COVID‐19 symptoms in our survey cohort were fatigue (288/309, 93.2%), pain including headache (218/309, 70.6%), and sleep–wake disturbances (mainly insomnia and excessive daytime sleepiness, 145/309, 46.9%). Post‐COVID‐19 syndrome had an impact on work ability, as more than half of the respondents (168/268, 62.7%) reported an inability to work, which lasted on average 26.6 weeks (95% CI 23.5–29.6, range 1–94, n = 168). Quality of life measured by WHO‐5 Well‐being Index was overall low in respondents with post‐COVID‐19 syndrome (mean, 95% CI 9.1 [8.5–9.8], range 1–25, n = 239). Conclusion: Fatigue, pain, and sleep–wake disturbances were the main symptoms of the post‐COVID‐19 syndrome in our cohort and had an impact on the quality of life and ability to work in a majority of patients. However, survey respondents reported a significant reduction in symptoms over 12 months. Post‐COVID‐19 syndrome remains a significant challenge. Further studies to characterize this syndrome and to explore therapeutic options are therefore urgently needed. [ABSTRACT FROM AUTHOR]

Objective: Intrathecal Immunoglobulin M synthesis (IgMIntrathecal Fraction (IF)+) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgMIF+ is associated with spinal cord manifestation and higher neuroaxonal damage in early MS. Methods: In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non‐spinal clinical syndrome (2) spinal vs cerebral T2‐weighted (T2w) and (3) contrast‐enhancing (CE) lesion counts with IgGIF+ (vs IgGIF−) or IgMIF+ (vs IgMIF−) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgGIF and IgMIF (>0% vs 0%, respectively): (1) OCGB−/IgGIF−/IgMIF−; (2) OCGB+/IgGIF−/IgMIF−; (3) OCGB+/IgGIF+/IgMIF−; and (4) OCGB+/IgGIF+/IgMIF+. Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters. Results: Patients with a spinal syndrome had a 8.36‐fold higher odds of IgMIF+ (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgMIF+ (but not of IgGIF+); this was not the case for cerebral lesions. OCGB+/IgGIF+/IgMIF+ category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01). Interpretation: Intrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022;91:814–820 [ABSTRACT FROM AUTHOR]

Keywords: disability; immunotherapy; MS; prediction score EN disability immunotherapy MS prediction score 792 795 4 04/07/22 20220501 NES 220501 Survival analysis of reaching EDSS >=4.0 based on RoAD score >=4 (dashed line) and <4 (solid line) by Cox regression analysis. Treatment response scoring systems to assess long - term prognosis in self - injectable DMTs relapsing - remitting multiple sclerosis patients. Application of the "risk of ambulatory disability" (RoAD) score in a "real-world" single-center multiple sclerosis cohort. [Extracted from the article]

CdSe magic‐sized quantum dots (MSQDs) have been widely used as fluorescent probes in biological systems due to their excellent optical properties with a broader fluorescence spectrum and stable luminescence in biological media. However, they can be cytotoxic and alter the redox balance depending on the amounts of Cd2+ adsorbed on their surface. Thus, the present study aimed to evaluate whether increases in selenium concentration in the synthesis of CdSe‐MSQDs decrease the oxidative stress caused by Cd2+‐based quantum dots. CdSe‐MSQDs synthesized with different concentrations of selenium were investigated against oxidative stress in the brain of chicken embryos by examining total antioxidant capacity, lipid peroxidation, thiol, and glutathione contents, as well as the activities of glutathione peroxidase, superoxide dismutase (SOD), catalase (CAT), and glutathione reductase. In addition, the vascularization of the chorioallantoic membrane (CAM) analysis was performed. Higher selenium concentrations alter the surface defect levels (decrease free Cd2+) and controlled the oxidative effects of CdSe‐MSQDs by reducing the lipid peroxidation, restoring the glutathione defense system and the antioxidant enzymes SOD and CAT, and maintaining the vascular density of the CAM. The current findings reinforce the study of the effects of the presence of Cd2+ ions on the surface of quantum dots, changing toxicity, and aiming interesting strategies of nanomaterials in biological systems. [ABSTRACT FROM AUTHOR]

Background: Most case series of patients with ischemic stroke (IS) and COVID‐19 are limited to selected centers or lack 3‐month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3‐month outcomes of patients with IS and COVID‐19 in a nationwide stroke registry. Methods: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID‐19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3‐month outcome of SARS‐CoV‐2 polymerase chain reaction‐positive (PCR+) IS patients to SARS‐CoV‐2 PCR− and/or asymptomatic non‐tested IS patients. Results: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID‐19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08–5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14–0.99, p = 0.049). COVID‐19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS‐adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96–3.58, p = 0.07). Conclusions: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID‐19 was relatively rare. COVID+ patients more often had multi‐territory stroke and less often cryptogenic stroke, and their 3‐month functional outcome tended to be worse. [ABSTRACT FROM AUTHOR]

Background and purpose: In Switzerland, the COVID‐19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. Methods: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3‐month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. Results: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13–April 26 of the years 2018–2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). Conclusions: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained. [ABSTRACT FROM AUTHOR]

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti‐inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute‐1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma. [ABSTRACT FROM AUTHOR]

Background and purpose: Postural tachycardia syndrome (POTS) is a form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. Recently, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune‐mediated. The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory immune‐mediated POTS. Methods: We retroactively assessed the effect and tolerance of monthly administered IVIG in six patients using autonomic function testing, standardized symptom questionnaires, and patients' symptom diaries both before and 6 months into IVIG treatment. Objective outcome measures included heart rate increase after 10 min of head‐up tilt as well as duration and anhidrotic area in a thermoregulatory sweat test. Subjective outcome measures were patient reports and symptom ratings from the symptom questionnaire. Results: All patients responded to immunomodulatory treatment, regardless of disease duration. After 6 months of IVIG, symptom severity was reduced by nearly 40%. Autonomic function testing showed improved cardiovascular functioning by 50% and a reduction of anhidrotic areas by one third. Overall, tolerance of IVIG treatment was poor, but could be improved by a reduction in infusion rate, premedication with steroids, and additional intravenous hydration. Conclusions: Using subjective but also standardized objective measures, the case series describes promising effects of IVIG treatment in POTS patients with immune‐mediated dysautonomia. By reducing the infusion rate, pretreatment with steroids, and intravenous hydration, tolerance could be improved, and no patient had to discontinue the treatment. [ABSTRACT FROM AUTHOR]

Aims: Myelin oligodendrocyte glycoprotein antibodies (MOG‐IgG) have been proposed to define "MOG encephalomyelitis" (MOG‐EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. Methods: We retrospectively analyzed patients with borderline/positive MOG‐IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG‐EM diagnosis. Para‐/clinical parameters were described and analyzed with chi‐square test. Results: In total, 37 patients fulfilled MOG‐EM diagnostic criteria (female‐to‐male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5‐40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG‐IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as "possible" MOG‐EM. Of these, we classified 13 patients as "unlikely" MOG‐EM in the presence of the red flag "borderline MOG‐IgG" with negative MOG‐IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF‐)—specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG‐EM (P =.0005). Conclusion: Evaluation of diagnostic and red flag criteria, MOG‐IgG retesting (incl. change of assay), and CSF‐specific OCB are relevant in clinical routine cohorts to differentiate MOG‐EM from MS. [ABSTRACT FROM AUTHOR]

Increased COVID-19 severity was also demonstrated by an analysis of a more homogenous cohort of MS patients treated in France and Italy8 demonstrating an odds ratio (OR) of 2.05 (95%CI 1.39-3.02). Despite the majority of patients (35/51) having a mild-to-moderate disease course, 16/51 were hospitalized, 10/51 had a severe disease course, and 3/51 died.5 Despite small patient numbers, 3/51 exceeds the worldwide COVID-19 fatality rates (1.5%6; MS specific 3.3% (95%-confidence interval (95%CI), 2.5%-4.3%7). Is COVID-19 severity associated with reduction in T lymphocytes in anti-CD20-treated people with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder?. [Extracted from the article]

As the outsourced internal audit function (IAF) and real earnings management are attracting widespread attention among firms, it is vital for stakeholders to understand how these two practices affect the quality of financial reporting. This study examines how the expertise of an external IAF provider reduces real earnings management. Using a pooled panel data regression of 928 firm‐observations, we find that the external IAF provider's firm‐specific expertise is significantly associated with lower real earnings management. Conversely, we report no such association for external IAF providers with industry expertise. These findings are robust under a battery of sensitive analyses. The results of additional analyses show that the industry and firm‐specific expertise of external IAF provider interact with each other, resulting in a significant reduction in real earnings management. We also find significant differences in the IAF quality between big4 and second‐tier audit firms in which the latter are associated with lower real earnings management and the former with higher real earnings management. Finally, we observe low real earnings management for important clients and/or those with influential CEOs if the external IAF provider has firm‐specific expertise. [ABSTRACT FROM AUTHOR]

This publication is focused on the structural origin of viscoelasticity in Langmuir monolayers. To improve the understanding of the structural origin of viscoelasticity of surfactant films, we systematically studied interfacial films of different sorbitan esters with saturated (Span 60 and 65) and unsaturated (Span 80 and 85) paraffin chains by means of surface rheology, Langmuir isotherms, X‐ray reflectometry (XRR), and Brewster angle microscopy (BAM). The results of two‐dimensional shear rheological measurements revealed the existence of temporarily cross‐linked networks. In dynamic BAM experiments, we observed a swinging motion of the monolayers as a result of a sudden externally initiated mechanical perturbation. The viscoelastic film response, which relaxed with time as the external force vanished, could be traced back to the presence of foam‐like supramolecular structures that interlinked solid‐condensed domains. The temperature dependence of the elastic response implied that the solid domains decomposed at temperatures close to the bulk melting point of Span 60 and Span 65. We concluded that insoluble surfactants formed solid domains at the interface, which were linked with each other by nonsolid areas, giving viscoelastic films. These newly discovered insights into coherent film formations could provide new opportunities for designing mechanically stable surfactant interfaces. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Multiple sclerosis (MS) is an autoimmune disease of the CNS, which predominantly affects women. Studies investigating the sex distribution in MS are sparse. We aim to analyze the female‐to‐male ratio (F/M ratio) in different MS phenotypes in association with age at diagnosis and year of birth. Methods: We performed a retrospective cross‐sectional analysis by cumulating data (sex, year of birth, age at diagnosis, and MS phenotypes) from unpublished and published studies of the participating centers. Results: Datasets of 945 patients were collected. The overall F/M ratio was 1.9:1.0 and female preponderance was present in all phenotypes except for primary progressive MS (PPMS), in which men were predominantly affected (F/M ratio: 0.5:1.0). Female preponderance declined with increasing age at diagnosis and was no longer present in relapsing‐remitting MS (RRMS) patients > 58 years of age. Conclusion: Our data demonstrate an age dependency of female preponderance in MS except for PPMS. This could be influenced by the lifecycle of sex hormone secretion in women. In PPMS, a male preponderance was observed in all age‐groups, which might point to pathophysiological mechanisms being less influenced by sex hormones. [ABSTRACT FROM AUTHOR]

Summary: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that can infect almost all warm‐blooded species and induce a chronic infection in human hosts. The aim of this work was to investigate Th1, Th2, Th17 and Treg polarization, induced by four important T. gondii antigens (SAG1, ROP1, GRA8 and MAG1) in acutely and chronically infected patients. For this purpose, SAG1, ROP1, GRA8 and MAG1 were expressed as recombinant proteins, purified, and used to evaluate the proinflammatory and regulatory immune response profiles in seropositive and seronegative individuals. Our results show that SAG1 and ROP1 elicited a proinflammatory profile (INF‐γ, IL‐12 and IL‐17) in individuals in the acute phase, whereas MAG1 and GRA8 induced a regulatory pattern (Treg and TGF‐β) in chronically infected patients. These results reveal fundamental differences in T‐cell polarization induced by T. gondii antigens, which could have important implications in the immunopathogenesis of the disease and in future proposals of therapeutic strategies. [ABSTRACT FROM AUTHOR]

We have gained new insight into the so-called hydrophobic gap, a molecularly thin region of decreased electron density at the interface between water and a solid hydrophobic surface, by X-ray reflectivity experiments and molecular dynamics simulations at different hydrostatic pressures. Pressure variations show that the hydrophobic gap persists up to a pressure of 5 kbar. The electron depletion in the interfacial region strongly decreases with an increase in pressure, indicating that the interfacial region is compressed more strongly than bulk water. The decrease is most significant up to 2 kbar; beyond that, the pressure response of the depletion is less pronounced. [ABSTRACT FROM AUTHOR]

Objective: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).Methods: sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.Results: sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease-modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034).Interpretation: These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857-870. [ABSTRACT FROM AUTHOR]

Diagnosis of true umbilical knot is not frequent but it has a significant emotional impact on the parturient and doctor. Regardless of its negative perinatal effects when true umbilical knot (TUK) is not diagnosed, the prenatal echographic evaluation rarely detects this pathology. [Extracted from the article]

Chronic hepatitis B virus (HBV) infection involves liver damage resulting in continuous cell injury and death. During HBV infection, hepatocytes exhibit changes in death receptor expression and in their susceptibility to death. These changes are observed not only in infected cells but also in bystander cells. Because excess viral surface protein (HBsAg) is secreted in large amounts as soluble particles containing preS proteins, the role of soluble preS1/2 in hepatocyte (HepG2) death modulation is an important issue to be explored. An increase of cell death induced by preS1/2 was observed. Also, cell death was associated with the down-regulation of FLIP and activation of caspase 8, caspase 9, and BID. Additionally, hepatocytes exhibited a sensitization to death mediated by the Fas receptor. These results, may contribute to understanding the role of envelope proteins (preS1/2) in the pathogenesis of HBV infection. J. Med. Virol. 86:496-504, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

CA3 pyramidal cells receive three main excitatory inputs: the first one is the mossy fiber input, synapsing mainly on the proximal apical dendrites. Second, entorhinal cortex cells form excitatory connections with CA3 pyramidal cells via the perforant path in the stratum lacunosum moleculare. The third input involves the ipsi-and contralateral connections, termed the associational/commissural (A/C) pathway terminating in the stratum radiatum of CA3, thus forming a feedback loop within this region. Since this excitatory recurrent synapse makes the CA3 region extremely prone to seizure development, understanding the regulation of synaptic strength of this connection is of crucial interest. Several studies suggest that kainate receptors (KAR) play a role in the regulation of synaptic strength. Our aim was to characterize the influence of KAR on A/C synaptic transmission: application of ATPA, a selective agonist of the GluK1 KAR, depressed the amplitude fEPSP without affecting the size of the fiber volley. Blockade of GABA receptors had no influence on this effect, arguing against the influence of interneuronal KARs. Pharmacological and genetic deletion studies could show that this effect was selectively due to GluK1 receptor activation. Several lines of evidence, such as PPF changes, coefficient of variance-analysis and glutamate uncaging experiments strongly argue for a presynaptic locus of suppression. This is accompanied by an ATPA-mediated reduction in Ca2+ influx at excitatory synaptic terminals, which is most likely mediated by a G-Protein dependent mechanism, as suggested by application of pertussis toxin. Finally, analysis of miniature EPSCs in the presence and absence of extracellular Ca2+ suggest that presynaptic KAR can also reduce transmitter release downstream and therefore independent of Ca2+ influx. © 2010 Wiley Periodicals, Inc., Inc. [ABSTRACT FROM AUTHOR]

Universal design has the potential to transform universities into truly egalitarian institutions that accommodate all users regardless of their size, age, or physical capabilities, allowing them to flourish, learn, and unleash their true potential. [ABSTRACT FROM AUTHOR]

The presence of myosin and dynein in the ovaries of both Apis mellifera and Scaptotrigona postica was investigated in extracts and in histological sections. In the ovary extracts, motor proteins, myosins V, VI and dynein were detected by Western blot. In histological sections, they were detected by immunocytochemistry, using a mouse monoclonal antibody against the intermediary chain of dynein and a rabbit polyclonal antibody against the myosin V head domain. The myosin VI tail domain was recognized by a pig polyclonal antibody. The results show that these molecular motors are expressed in the ovaries of both bee species with few differences in location and intensity, in regions where movement of substances is expected during oogenesis. The fact that antibodies against vertebrate proteins recognize proteins of bee species indicates that the specific epitopes are evolutionarily well preserved. [ABSTRACT FROM AUTHOR]

Therapeutic limitations, development of fungal drug resistance, drug-related toxicity, drug interactions and insufficient bioavailability of the currently available antifungal drugs have made the development of drugs necessary that would be able to treat the emerging fungal infections. The Cerrado is the second greater biome of Brazil and it was identified as one of the most distinguished biomes of South America, becoming an important source of innovative vegetal molecules to treat several conditions. Thus, the objective of this study was to evaluate the antifungal potential of Cerrado plants, mainly those used to treat infections and wounds. A total of 57 extracts were screened by the agar-well diffusion technique against Candida albicans and Trichophyton rubrum. The most promising extracts were tested in smaller concentrations and their minimal inhibitory concentrations (MIC) were determined by microdilution method. Results were analysed statistically byanova tests. Extracts of Kielmeyera coriacea, Renealmia alpinia, Stryphnodendron adstringens and Tabebuia caraiba were very active against T. rubrum, presented geometric means of the MIC values between 170.39 and 23.23 μg ml−1. Extracts of Cerrado plants are of particular interest as source of new agents for the treatment of dermatophytic infections. [ABSTRACT FROM AUTHOR]

The extracellular sulfatases Sulf1 and Sulf2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1- and Sulf2-deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1- and Sulf2-deficient mouse lines. In addition, Sulf1-specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non-redundant functions in vivo in the development and maintenance of the murine nervous system. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is an inherited disorder caused by defects in the NADPH oxidase complex, which generates superoxide, the precursor of hydrogen peroxide (H2O2) and other reactive oxygen derivatives with microbicidal activity. Because CGD patients are at risk of chronic inflammatory manifestations, including inflammatory bowel disease and autoimmune diseases, and it is not clear whether these pathologies are exclusively secondary to altered superoxide production, or whether distinct immunologic defects are involved, we explored cell proliferation, lymphocyte cell counts, immunoglobulin levels, presence of autoimmune antibodies and expression of costimulatory molecules in leukocytes from CGD patients. We found that CGD patients have a diminished phytohemagglutinin-induced proliferation of blood mononuclear cells. Following stimulation with PMA plus ionomycin, a reduced percentage of CD40L expression in T lymphocytes and a diminished expression of CD40 molecules in neutrophils were observed on leukocytes from these patients. Our results suggest an altered interplay between elements of innate and adaptive immunity in CGD patients, which may be reflected in an increased susceptibility to opportunistic infections. [ABSTRACT FROM AUTHOR]

Albarran B, Goncalves L, Salmen S, Borges L, Fields H. Soyano A, Montes H, Berrueta L. Profiles of NK, NKT cell activation and cytokine production following vaccination against hepatitis B. APMIS 2005;113:526–35. Human natural killer (NK) cells (CD56+ CD3−) represent crucial components of the innate immune system especially against viral infections and because their activation can modulate the outcome of the adaptive immune response. NKT cells (CD56+CD3+), a lymphocyte T population characterized by expression of surface markers of NK cells, are known to be abundant in the liver and their activation could be associated with hepatic injury. Using three-color flow cytometry to measure surface receptors and intracellular cytokines, we have explored early activation signals and cytokine production in NK and NKT cells within a group of hepatitis B vaccinated and non-vaccinated individuals. A specific increase of the CD56bright cell population, the activation receptor CD69 and IFN-γ, was observed in NK cells following incubation with recombinant HBsAg in responders to vaccination. Comparable results were observed in NKT cells showing an increment of CD69, CD25, IL-2 and IFN-γ expression in responder subjects. These parameters were statistically diminished in non-responder individuals (p<0.05) in both groups of cells. These results demonstrate a diminished activation of these cells in non-responders to the vaccine, suggesting that NK and NKT cells play an important role in the immune response following hepatitis B vaccination. [ABSTRACT FROM AUTHOR]

Examines the association of dermatophagoides with asthma in sensitized atopic subjects in Venezuela. Investigation on the microscopic identification of mites in dust; Measurement of humidity; Variation of antigen concentration.

Since the early 1970s, the World Bank has recognized that economic growth alone will not reduce poverty. Yet it has not fully accepted the fact that effective poverty reduction requires a 'learning process approach', rather than the 'blueprint approach' commonly used by development agencies. To facilitate the learning process approach, the Bank should consider using qualified intermediary, grass-roots, and non-governmental organizations (NGOs); stimulating pluralism and competition; and encouraging cooperation between central and local institutions. However, helping the poor is going to require more administrative resources than heretofore provided, making funds available for careful and flexible project design, staff exposure to poverty conditions and programmes, training in and recruitment of appropriate inter-disciplinary fields, monitoring and evaluation, and continual project revision. [ABSTRACT FROM AUTHOR]