Toward biophysical markers of depression vulnerability

A major difficulty with treating psychiatric disorders is their heterogeneity: different neural causes can lead to the same phenotype. To address this, we propose describing the underlying pathophysiology in terms of interpretable, biophysical parameters of a neural model derived from the electroencephalogram. We analyzed data from a small patient cohort of patients with depression and controls. Using DCM, we constructed biophysical models that describe neural dynamics in a cortical network activated during a task that is used to assess depression state. We show that biophysical model parameters are biomarkers, that is, variables that allow subtyping of depression at a biological level. They yield a low dimensional, interpretable feature space that allowed description of differences between individual patients with depressive symptoms. They could capture internal heterogeneity/variance of depression state and achieve significantly better classification than commonly used EEG features. Our work is a proof of concept that a combination of biophysical models and machine learning may outperform earlier approaches based on classical statistics and raw brain data

Multi-Modal Neuroimaging Analysis and Visualization Tool (MMVT)

Sophisticated visualization tools are essential for the presentation and exploration of human neuroimaging data. While two-dimensional orthogonal views of neuroimaging data are conventionally used to display activity and statistical analysis, three-dimensional (3D) representation is useful for showing the spatial distribution of a functional network, as well as its temporal evolution. For these purposes, there is currently no open-source, 3D neuroimaging tool that can simultaneously visualize desired combinations of MRI, CT, EEG, MEG, fMRI, PET, and intracranial EEG (i.e., ECoG, depth electrodes, and DBS). Here we present the Multi-Modal Visualization Tool (MMVT), which is designed for researchers to interact with their neuroimaging functional and anatomical data through simultaneous visualization of these existing imaging modalities. MMVT contains two separate modules: The first is an add-on to the open-source, 3D-rendering program Blender. It is an interactive graphical interface that enables users to simultaneously visualize multi-modality functional and statistical data on cortical and subcortical surfaces as well as MEEG sensors and intracranial electrodes. This tool also enables highly accurate 3D visualization of neuroanatomy, including the location of invasive electrodes relative to brain structures. The second module includes complete stand-alone pre-processing pipelines, from raw data to statistical maps. Each of the modules and module features can be integrated, separate from the tool, into existing data pipelines. This gives the tool a distinct advantage in both clinical and research domains as each has highly specialized visual and processing needs. MMVT leverages open-source software to build a comprehensive tool for data visualization and exploration.Comment: 29 pages, 10 figure

Use of complementary and alternative medicines by a sample of Turkish women for infertility enhancement: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Infertility patients are a vulnerable group that often seeks a non-medical solution for their failure to conceive. World-wide, women use CAM for productive health, but only a limited number of studies report on CAM use to enhance fertility. Little is known about traditional and religious forms of therapies that are used in relation to conventional medicine in Turkey. We investigated the prevalence and types of complementary and alternative medicine (CAM) used by infertile Turkish women for fertility enhancement.</p> <p>Methods</p> <p>A face-to-face questionnaire inquiring demographic information and types of CAM used for fertility enhancement were completed by hundred infertility patients admitted to a primary care family planning centre in Van, Turkey between January and July 2009.</p> <p>Results</p> <p>The vast majority of infertile women had used CAM at least once for infertility. CAM use included religious interventions, herbal products and recommendations of traditional "hodja's" (faith healers). Of these women, 87.8% were abused in the last 12 months, 36.6% felt not being supported by her partner and 80.5% had never spoken with a physician about CAM.</p> <p>Conclusions</p> <p>Infertile Turkish women use complementary medicine frequently for fertility enhancement and are in need of information about CAM. Religious and traditional therapies are used as an adjunct to, rather than a substitute for, conventional medical therapy. Physicians need to approach fertility patients with sensitivity and should be able to council their patients about CAM accordingly.</p

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein-specific Th1 response with a diverse TCR repertoire.

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein-specific CD4+ T cell helper type 1 (Th1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor (TCR) β sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4+ and CD8+ T cell responses. Overall, AZD1222 vaccination induced a polyfunctional Th1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein

Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per millilite

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care

Assisted reproductive technologies in India: the views of practitioners.

BACKGROUND: This article documents the context of Assisted Reproductive Technology/ies (ART) services and providers' perceptions regarding services offered in India. The objective is to facilitate understanding of critical issues and relevant concerns. METHODS: A postal survey conducted with a sample of 470 gynaecologists and in-depth interviews with 39 gynaecologists in four cities. RESULTS: ART clinics have proliferated in cities and towns; they are commercialised and the quality of treatment is variable. Most providers perceived that patients lack knowledge about infertility and ART, costs are high, investigations unnecessarily repeated and success rates low. ART providers do not have clear selection criteria, some lack rigorous specialised training and infrastructure and most are deficient in record-keeping and counselling and lack transparency. Monitoring and regulation by appropriate authorities are also lacking. CONCLUSION: Both providers and regulatory authorities need to look critically at exploitation of patients and commercialisation, excessive costs, lack of information, informed consent, and transparency, counselling, unethical practices, variations in quality of treatment and ensuring proper monitoring and regulation