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Purpose To assess the accuracy of preoperative sonographic staging for prediction of limited axillary disease (LAD, one or two metastatic lymph nodes) and to identify factors associated with high prediction–pathology concordance in patients with early-stage breast cancer meeting the Z0011 criteria. Materials and Methods Patients treated between January 2015 and January 2020 were included in this retrospective, multicentric analysis of prospectively acquired service databases. The accuracy of LAD prediction was assessed separately for patients with one and two suspicious lymph nodes on preoperative sonography. Test validity outcomes for LAD prediction were calculated for both groups, and a multivariate model was used to identify factors associated with high accuracy of LAD prediction. Results Of 2059 enrolled patients, 1513 underwent sentinel node biopsy, 436 primary and 110 secondary axillary dissection. For LAD prediction in patients with one suspicious lymph node on preoperative ultrasound, sensitivity was 92% (95% CI 87–95%), negative predictive value (NPV) was 92% (95% CI 87–95%), and the false-negative rate (FNR) was 8% (95% CI 5–13%). For patients with two preoperatively suspicious nodes, the sensitivity, NPV, and FNR were 89% (95% CI 84–93%), 73% (62–83%), and 11% (95% CI 7–16%), respectively. On multivariate analysis, the number of suspicious lymph nodes was associated inversely with correct LAD prediction ([OR 0.01 (95% CI 0.01–0.93), p ≤ 0.01]. Conclusions Sonographic axillary staging in patients with one metastatic lymph node predicted by preoperative ultrasound showed high accuracy and a false-negative rate comparable to sentinel node biopsy for prediction of limited axillary disease.

Purpose As data on this topic are sparse and contradictory, we aimed to ascertain the opinions of the members of the German Society of Gynecologic Endoscopy (AGE) regarding the use of robotic surgery in the treatment of ovarian malignancies. Methods In 2015, an anonymous questionnaire was sent to AGE members to assess their views on the treatment of ovarian malignancies by robotic surgery according to T stage and the current treatment practices in their facilities. Results Of the 228 respondents, 132 (58%) were fellows or attending physicians and 156 (68%) worked at university hospitals or tertiary referral centers. Most [n = 218 (96%)] respondents reported treating Conclusion The majority of AGE members surveyed considered robotic surgery to be an option for the treatment of T1 ovarian malignancies and borderline ovarian tumors. However, prospective randomized studies are needed to determine the relevance of robotic surgery in this context.

Increasing evidence suggests a role of the gut microbiota in patients’ response to medicinal drugs. In our recent study, we combined genomics of human gut commensals and gnotobiotic animal experiments to quantify microbiota and host contributions to drug metabolism. Informed by experimental data, we built a physiology-based pharmacokinetic model of drug metabolism that includes intestinal compartments with microbiome drug-metabolizing activity. This model successfully predicted serum levels of metabolites of three different drugs, quantified microbial contribution to systemic drug metabolite exposure, and simulated the effect of different parameters on host and microbiota drug metabolism. In this addendum, we expand these simulations to assess the effect of microbiota on the systemic drug and metabolite levels under conditions of altered host physiology, microbiota drug-metabolizing activity or physico-chemical properties of drugs. This work illustrates how and under which circumstances the gut microbiome may influence drug pharmacokinetics, and discusses broader implications of expanded pharmacokinetic models.

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. ispartof: NATURE MEDICINE vol:28 issue:2 pages:303-+ ispartof: location:United States status: published

Purpose The purpose of this survey was to assess medical students’ opinions about online learning programs and their preferences for specific teaching formats during COVID 19 pandemic. Methods Between May and July 2020, medical students who took an online gynecology and obstetrics course were asked to fill in a questionnaire anonymously. The questionnaire solicited their opinions about the course, the teaching formats used (online lectures, video tutorials featuring real patient scenarios, and online practical skills training), and digital learning in general. Results Of 103 students, 98 (95%) submitted questionnaires that were included in the analysis. 84 (86%) students had no problem with the online course and 70 (72%) desired more online teaching in the future. 37 (38%) respondents preferred online to traditional lectures. 72 (74%) students missed learning with real patients. All digital teaching formats received good and excellent ratings from > 80% of the students. Conclusion The survey results show medical students’ broad acceptance of the online course during COVID 19 pandemic and indicates that digital learning options can partially replace conventional face-to-face teaching. For content taught by lecture, online teaching might be an alternative or complement to traditional education. However, bedside-teaching remains a key pillar of medical education.

Background Data on antimicrobial resistance mechanisms are scanty for Cedecea spp., with very variable antibiotic resistance patterns documented. Here we report the first in vivo resistance evolution of a C. davisae clinical isolate in a patient with a complex hand trauma and provide insight in the resistance mechanism, leading to therapeutic implications for this pathogen. Case presentation Cedecea davisae was isolated from a patient with hand trauma during a first surgical debridement. Six days after primary surgical treatment and under antimicrobial treatment with amoxicillin-clavulanic acid and later cefepime, follow up cultures yielded C. davisae which demonstrated a resistance development. The susceptible parental isolate and its resistant derivative were characterized by whole genome sequencing, ampC, ompC and ompF by RT- PCR. The resistant derivative demonstrated an A224G SNP in ampD, the transcriptional regulator of ampC, leading to a His75Arg change in the corresponding AmpD protein. AmpC transcription of the resistant derivative was 362-times higher than the susceptible isolate. Transcription levels of ompF and ompC were 8.5-fold and 1.3-fold lower, respectively, in the resistant derivative. Downregulation of OmpF putatively resulted from a mutation in the presumed promoter region upstream of the dusB-Fis operon, a proposed regulator for ompF. Conclusions This case demonstrates the in vivo resistance development of C. davisae within 7 days similar to that of the members of the Enterobacter cloacae complex. Our findings add valuable information for future therapeutic management of these opportunistic pathogens as they warrant the same empirical treatment as AmpC producers.

BACKGROUND AND OBJECTIVES: To assess the concordance and discordance between the core Alzheimer disease (AD) CSF biomarkers and [(18)F]fluorodeoxyglucose (FDG)-PET patterns evaluated clinically in memory clinic patients who meet appropriate use criteria for AD biomarker investigations. METHODS: We retrospectively assessed participants with atypical and/or early-onset dementia evaluated at a tertiary care memory clinic. All individuals underwent CSF evaluations for Aβ42, phosphorylated tau (P-tau181) and total tau, and brain [(18)F]FDG-PET. [(18)F]FDG-PET data were visually interpreted by 2 nuclear medicine experts as being consistent with AD or non-AD. CSF biomarker results were similarly grouped into AD biomarker positive/negative. Contingency tables and Kappa coefficients were used to establish the level of agreement and disagreement between CSF and [(18)F]FDG-PET results in all individuals. RESULTS: One hundred thirty-six individuals had both [(18)F]FDG-PET and lumbar puncture performed as part of the early-onset and/or atypical dementia assessments. [(18)F]FDG-PET showed a pattern suggestive of AD in 43% of patients, while CSF biomarkers showed results consistent with AD in 57% of participants. In patients who met criteria for AD biomarker investigations, we found that [(18)F]FDG-PET was discordant with CSF AD biomarkers in nearly 20% of cases; 12% of individuals with [(18)F]FDG-PET scans consistent with AD had AD-negative CSF results; and 7% of individuals with [(18)F]FDG-PET scans not consistent with AD had AD-positive CSF results, potentially suggesting atypical AD variants or less advanced neurodegeneration. [(18)F]FDG-PET discriminated patients with an AD-positive CSF profile from patients with an AD-negative profile with a sensitivity and specificity higher than 80% (sensitivity: 81%, 95% CI = 71–88%, SP: 81%, 95% CI = 68–89%). Furthermore, [(18)F]FDG-PET had a positive predictive value of 87% (95% CI = 78–93%) and a negative predictive value of 72% (95% CI = 60–82%). DISCUSSION: CSF and [(18)F]FDG-PET disagreed in nearly 20% of the cases studied in this clinical series. While CSF Aβ42 and P-tau181 biomarkers are specific for AD, the topographical information from [(18)F]FDG-PET may provide complementary information.

Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.

To assess the change of body mass index (BMI), muscle mass, visceral and subcutaneous fat in patients with metastatic breast cancer. In this retrospective chart analysis, patients with metastatic breast cancer as initial diagnosis between 2012 and 2016 were analyzed. Patients had received either chemotherapy (CTH) or endocrine therapy (ETH) according to the German S3 Guideline. BMI was calculated from the patients’ weight and height. Change of muscle mass, visceral and subcutaneous fat was determined by comparing the surface area of these tissues on transverse CT images at the level of the third lumbar vertebrae (L3) at baseline and during treatment. A total of 45 patients were included in the study, 29 on CTH and 16 on ETH. BMI, visceral and subcutaneous fat remained stable over time for both treatment groups. When taking both treatment groups together, muscle mass decreased significantly by 5.0 ± 2.5 cm2 per year (p

Background In the COVID-19 pandemic, Switzerland introduced broad nationwide face mask mandates only by October 2020, later than other Western European countries. This study aims to assess the underlying values and considerations of individuals to wear face masks in the absence of face mask mandates in the COVID-19 pandemic in German-speaking Switzerland. Methods As part of the “Solidarity in times of a pandemic” (SolPan) research commons, we interviewed 31 participants living in the German-speaking part of Switzerland in April 2020 and 25 of them again in October 2020. Qualitative inductive thematic analysis was applied for data analysis and interpretation. Public health ethics principles guided the interpretation and organization of findings. Results Five themes were identified: Trust and governmental policy; perceived benefits of mask-wearing; perceived risks of mask-wearing; social exclusion and prejudice; and decision-making in the absence of mandates. In light of increasing infection rates in October 2020, many participants started to consider the benefits higher than the risks and were willing to accept face mask mandates in that context, despite earlier reservations. Conclusions The absence of face mask mandates underline individual autonomy but may also suppress personal responsibility due to social influence. Face masks are only temporarily acceptable in liberal Western societies and face mask mandates should be enforced only when epidemiologically necessary. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-021-12215-4.

OBJECTIVE Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p

Purpose The aims of this study were to determine the incidence of intraoperative and postoperative complications of laparoscopic gynecological interventions and to identify risk factors for such complications. Methods All patients who underwent laparoscopic interventions from September 2013 to September 2017 at the Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Hospital were identified retrospectively using a prospectively compiled clinical database. Binary logistic regression analysis was used to identify independent risk factors for intra- and postoperative complications. Results Data from 3351 patients were included in the final analysis. Overall, 188 (5.6%) intraoperative and 219 (6.5%) postoperative complications were detected. On multivariate analysis, age [odds ratio (OR), 1.03; 95% confidence interval (CI) 1.01–1.04], surgery duration (OR, 1.02; 95% CI 1.02–1.03), carbon dioxide use (OR, 0.99; 95% CI 0.99–1.00), and surgical indication (all p ≤ 0.01) were independent risk factors for intraoperative and duration of surgery (OR, 1.01; 95% CI 1.01–1.02; p ≤ 0.01), carbon dioxide use (OR, 0.99; 95% CI 0.99–1.00; p ≤ 0.01), hemoglobin drop (OR, 1.41; 95% CI 1.21–1.65; p ≤ 0.01), and ASA status (p = 0.04) for postoperative complications. Conclusion In this large retrospective analysis with a generally low incidence of complications (5.6% intraoperative and 6.5% postoperative complications), a representative risk collective was identified: Patients aged > 38 years, surgery duration > 99 min, benign or malignant adnex findings were at higher risk for intraoperative and patients with surgery duration > 94 min, hemoglobin drop > 2 g/dl and ASA status III at higher risk for postoperative complications.

Purpose Vaginal cuff dehiscence (VCD) is one of the major surgical complications following hysterectomy with data on incidence rates varying largely and studies assessing risk factors being sparse with contradictive results. The aim of this study was to assess the incidence rate of and risk factors for VCD in a homogenous cohort of women treated for benign uterine pathologies via total laparoscopic hysterectomy (TLH) with standardized follow-up. Methods All patients undergoing TLH at the Department of Gynecology and Obstetrics, Saarland University Hospital between November 2010 and February 2019 were retrospectively identified from a prospectively maintained service database. Results VCD occurred in 18 (2.9%) of 617 patients included. In univariate and multivariate analyses, a lower level of surgeon laparoscopic expertise (odds ratio 3.19, 95% confidence interval (CI) 1.0–9.38; p = 0.03) and lower weight of removed uterus (odds ratio 0.99, 95% CI 0.98–0.99; p = 0.02) were associated positively with the risk of VCD. Conclusion In this homogenous cohort undergoing TLH, laparoscopic expertise and uterine weight influenced the risk of postoperative VCD. These findings might help to further reduce the rate of this complication.

Early sensory deprivation, such as deafness, shapes brain development in multiple ways. Deprived auditory areas become engaged in the processing of stimuli from the remaining modalities and in high-level cognitive tasks. Yet, structural and functional changes were also observed in non-deprived brain areas, which may suggest the whole-brain network changes in deaf individuals. To explore this possibility, we compared the resting-state functional network organization of the brain in early deaf adults and hearing controls and examined global network segregation and integration. Relative to hearing controls, deaf adults exhibited decreased network segregation and an altered modular structure. In the deaf, regions of the salience network were coupled with the fronto-parietal network, while in the hearing controls, they were coupled with other large-scale networks. Deaf adults showed weaker connections between auditory and somatomotor regions, stronger coupling between the fronto-parietal network and several other large-scale networks (visual, memory, cingulo-opercular and somatomotor), and an enlargement of the default mode network. Our findings suggest that brain plasticity in deaf adults is not limited to changes in the auditory cortex but additionally alters the coupling between other large-scale networks and the development of functional brain modules. These widespread functional connectivity changes may provide a mechanism for the superior behavioral performance of the deaf in visual and attentional tasks. Electronic supplementary material The online version of this article (10.1007/s11682-020-00346-y) contains supplementary material, which is available to authorized users.

It has been proposed that the auditory cortex in the deaf humans might undergo task-specific reorganization. However, evidence remains scarce as previous experiments used only two very specific tasks (temporal processing and face perception) in visual modality. Here, congenitally deaf/hard of hearing and hearing women and men were enrolled in an fMRI experiment as we sought to fill this evidence gap in two ways. First, we compared activation evoked by a temporal processing task performed in two different modalities, visual and tactile. Second, we contrasted this task with a perceptually similar task that focuses on the spatial dimension. Additional control conditions consisted of passive stimulus observation. In line with the task specificity hypothesis, the auditory cortex in the deaf was activated by temporal processing in both visual and tactile modalities. This effect was selective for temporal processing relative to spatial discrimination. However, spatial processing also led to significant auditory cortex recruitment which, unlike temporal processing, occurred even during passive stimulus observation. We conclude that auditory cortex recruitment in the deaf and hard of hearing might involve interplay between task-selective and pluripotential mechanisms of cross-modal reorganization. Our results open several avenues for the investigation of the full complexity of the cross-modal plasticity phenomenon.SIGNIFICANCE STATEMENTPrevious studies suggested that the auditory cortex in the deaf may change input modality (sound to vision) while keeping its function (e.g., rhythm processing). We investigated this hypothesis by asking deaf or hard of hearing and hearing adults to discriminate between temporally and spatially complex sequences in visual and tactile modalities. The results show that such function-specific brain reorganization, as has previously been demonstrated in the visual modality, also occurs for tactile processing. On the other hand, they also show that for some stimuli (spatial) the auditory cortex activates automatically, which is suggestive of a take-over by a different kind of cognitive function. The observed differences in processing of sequences might thus result from an interplay of task-specific and pluripotent plasticity.

Background The main German-speaking countries (Germany, Austria, and Switzerland) have implemented digital contact tracing apps to assist the authorities with COVID-19 containment strategies. Low user rates for these apps can affect contact tracing and, thus, its usefulness in controlling the spread of the novel coronavirus. Objective This study aimed to assess the early perceptions of people living in the German-speaking countries and compare them with the frames portrayed in the newspapers during the first wave of the COVID-19 pandemic. Methods We conducted qualitative interviews with 159 participants of the SolPan project. Of those, 110 participants discussed contact tracing apps and were included in this study. We analyzed articles regarding contact tracing apps from 12 newspapers in the German-speaking countries. Results Study participants perceived and newspaper coverage in all German-speaking countries framed contact tracing apps as governmental surveillance tools and embedded them in a broader context of technological surveillance. Participants identified trust in authorities, respect of individual privacy, voluntariness, and temporary use of contact tracing apps as prerequisites for democratic compatibility. Newspapers commonly referenced the use of such apps in Asian countries, emphasizing the differences in privacy regulation among these countries. Conclusions The uptake of digital contact tracing apps in German-speaking countries may be undermined due to privacy risks that are not compensated by potential benefits and are rooted in a deeper skepticism towards digital tools. When authorities plan to implement new digital tools and practices in the future, they should be very transparent and proactive in communicating their objectives and the role of the technology—and how it differs from other, possibly similar, tools. It is also important to publicly address ethical, legal, and social issues related to such technologies prior to their launch.

Numerous school-based prevention programs have been developed by scientists and practitioners to address sexual violence in adolescence. However, such programs struggle with two major challenges. First, the effectiveness of many well-established practitioner programs has not been rigorously evaluated. Second, effective scientific programs may be hard to implement into everyday school practice. Combining the knowledge of scientists and practitioners in a scientist-practitioner program could be a helpful compromise. The aim of the present study is to evaluate the effects of a scientist-practitioner program and a practitioner program using a cluster-randomized experimental design. Twenty-seven school classes were randomly assigned to either one of two programs or a control group. Outcome variables (knowledge, attitudes, behavior, and iatrogenic effects) were assessed at pretest, posttest, and a 6-month follow-up for 453 adolescents (55% female, Mage = 14.18). Short-term effects were found in both programs regarding general knowledge, knowledge of professional help, and victim-blaming attitudes. Long-term effects were found in both programs regarding general knowledge and knowledge of professional help and, in the practitioner program, in a reduction of victimization. No other effects were found on attitudes and behavior. No iatrogenic effects in the form of increased anxiety were found. Both the scientist-practitioner and the practitioner program show promise for the prevention of sexual violence in adolescence; in particular, the practitioner program may be a more cost-effective method.

Determining antigen specificity is vital for understanding B cell biology and for producing human monoclonal antibodies. We describe here a powerful method for identifying B cells that recognize membrane antigens expressed on cells. The technique depends on two characteristics of the interaction between a B cell and an antigen-expressing cell: antigen-receptor-mediated extraction of antigen from the membrane of the target cell, and B cell activation. We developed the method using influenza hemagglutinin as a model viral membrane antigen, and tested it using acetylcholine receptor (AChR) as a model membrane autoantigen. The technique involves co-culturing B cells with adherent, bioorthogonally labeled cells expressing GFP-tagged antigen, and sorting GFP-capturing, newly activated B cells. Hemagglutinin-specific B cells isolated this way from vaccinated human donors expressed elevated CD20, CD27, CD71, and CD11c, and reduced CD21, and their secreted antibodies blocked hemagglutination and neutralized viral infection. Antibodies cloned from AChR-capturing B cells derived from patients with myasthenia gravis bound specifically to the receptor on cell membrane. The approach is sensitive enough to detect antigen-specific B cells at steady state, and can be adapted for any membrane antigen.

International audience; Usually transmitted via respiratory droplets, parvovirus B19 (B19V) can also be acquired by blood transfusion especially because of viral persistence, resistance to blood treatment procedures, and high viral load during the early infection phase. This is particularly problematic in immunocompromised or anemic patients where the infection can have a severe outcome. As B19V DNA was detected in blood donations from South Brazil during a viral metagenomic survey performed by Next-Generation Sequencing, the objective of this retrospective study was to evaluate the seroprevalence, B19V DNA presence and circulating genotypes in a Hospital Blood Transfusion Service in Santa Maria city in South Brazil (Rio Grande do Sul state). Among 480 volunteer blood donors, 53.9% (n = 258 of 479) were anti-B19V IgG-positive, and 9 (1.9%) plasma samples presented B19V DNA. In almost all cases (n = 7 of 9, 77.8%), B19V DNA load was accompanied by the presence of anti-B19V IgG suggesting a persistent infection. The sequencing of the strains demonstrated that all belong to genotype 1 which is the most prevalent worldwide. The analysis of the recipient information of the positive for B19V DNA units revealed no related posttransfusion adverse effects. Our results demonstrate for the first time, B19V seroprevalence, viral load, and genotypes among blood donors from South Brazil and give a light for the circulation and impact of this B19V in this part of the country.

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity.

Objective Human pegivirus (HPgV-1, GBV-C) is classified within the Pegivirus genus of the Flaviviriade family. The natural history of HPgV-1 infection is still unclear, however, the main route of viral transmission seems to be the parenteral one. The detection of HPgV-1 viremia in blood donors without parenteral exposure demonstrates that other routes of HPgV-1 transmission might also exist. The objective of the present study was to evaluate the prevalence of HPgV-1 RNA and circulating genotypes among blood donors from a intra-hospital Hemotherapy Service localized in the Santa Maria city, central part of the Rio Grande do Sul State in the extreme South of Brazil. Methods Blood samples were obtained from 373 volunteer blood donors and tested for the presence of HPgV-1 RNA. All positive for RNA samples were submitted to sequencing and phylogenetic analysis. Results The prevalence of the HPgV-1 RNA was 5.9% (22/373). The performed phylogenetic analysis demonstrated a predominant detection of genotype 2 with its both subgenotype forms (95.5% of all isolates i.e 54.5% belonging to subgenotype 2 A and 40.9% belonging to subgenotype 2B). Only one sequence was classified as genotype 3 (1/22, 4.5%). Conclusions Our study demonstrates the circulation pattern and genotypes of HPgV-1 among volunteer blood donors of South Brazil, and adds to the global knowledge of the natural history and possible transmission routes of this viral agent with putative impact on the area of hemotherapy.

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior–lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain.

Training can induce cross-modal plasticity in the human cortex. A well-known example of this phenomenon is the recruitment of visual areas for tactile and auditory processing. It remains unclear to what extent such plasticity is associated with changes in anatomy. Here we enrolled 29 sighted adults into a nine-month tactile Braille-reading training, and used voxel-based morphometry and diffusion tensor imaging to describe the resulting anatomical changes. In addition, we collected resting-state fMRI data to relate these changes to functional connectivity between visual and somatosensory-motor cortices. Following Braille-training, we observed substantial grey and white matter reorganization in the anterior part of early visual cortex (peripheral visual field). Moreover, relative to its posterior, foveal part, the peripheral representation of early visual cortex had stronger functional connections to somatosensory and motor cortices even before the onset of training. Previous studies show that the early visual cortex can be functionally recruited for tactile discrimination, including recognition of Braille characters. Our results demonstrate that reorganization in this region induced by tactile training can also be anatomical. This change most likely reflects a strengthening of existing connectivity between the peripheral visual cortex and somatosensory cortices, which suggests a putative mechanism for cross-modal recruitment of visual areas.

In the mammalian gut, bacteria compete for resources to maintain their populations, but the factors determining their success are poorly understood. We report that the human gut bacterium Bacteroides thetaiotaomicron relies on the stringent response, an intracellular signaling pathway that allocates resources away from growth, to survive carbon starvation and persist in the gut. Genome-scale transcriptomics, (13)C-labeling, and metabolomics analyses reveal that B. thetaiotaomicron uses the alarmone (p)ppGpp to repress multiple biosynthetic pathways and upregulate tricarboxylic acid (TCA) cycle genes in these conditions. During carbon starvation, (p)ppGpp triggers accumulation of the metabolite alpha-ketoglutarate, which itself acts as a metabolic regulator; alpha-ketoglutarate supplementation restores viability to a (p)ppGpp-deficient strain. These studies uncover how commensal bacteria adapt to the gut by modulating central metabolism and reveal that halting rather than accelerating growth can be a determining factor for membership in the gut microbiome.

We conducted a cross-sectional study nested within a cohort study with 276 postpartum women to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and the stressful life events (SLE) on the risk of postpartum depression (PPD) symptoms in a community sample. Participants were assessed between 45 and 90 days after delivery with the Edinburgh Postnatal Depression Scale (EPDS) and the Mini International Neuropsychiatric Interview (MINI). Data regarding socio-demographic variables, alcohol consumption, tobacco smoking and SLE occurring during pregnancy, were also collected. In the adjusted analysis, the women carrying the long (L) allele (LL) who experienced SLE showed higher prevalence ratios (PR) for PPD symptoms (EPDS ≥13) than those with two copies of the short (S) allele (SL) (PR = 9.91; 95% confidence interval: 1.70-57.87). In contrast, a trend of association was found between prior history of major depressive disorder (MDD) and the S allele carrier status (p = 0.07). No association was found between the formal diagnosis of current MDD and the 5-HTTLPR genotypes. In line with previous reports, we find in this sample that the L allele carrier status was associated with a heighten risk of depressive symptoms in postpartum when SLE were experienced during pregnancy.