Comparative studies on the cultivation, yield, and nutritive value of an edible mushroom, Pleurotus tuber-regium (Rumph. ex Fr.) Singer, grown under different agro waste substrates.

In the present study, Pleurotus tuber-regium (Rumph. ex Fr.) Singer collected from Keeriparai forest of Kanyakumari district, South India was cultivated using environmentally benign, low-cost agricultural waste residues (paddy straw, sugarcane bagasse, rice husk, and sawdust) as growth substrates. The main goal of this study was to assess the cultivation, yield, and nutritional value of P. tuber-regium fruiting bodies grown under different growth substrates. Spawn running time and time for primordia formation were found to be shorter in mushroom growing with paddy straw substrate compared to sawdust and sugarcane bagasse. A quick spawn run time was observed in paddy straw substrate (12 ± 1 day) followed by sugarcane bagasse (15 ± 1 day) and sawdust (23 ± 1 day). The primordia was well developed in the macrofungus grown with paddy straw substrate on 18 ± 1 day followed by sugarcane bagasse (22 ± 1 day) and sawdust (32 ± 1 day). Significantly higher yield of fruiting bodies with increased contents of protein and carbohydrate and low level of fat was obtained when P. tuber-regium was cultivated with paddy straw substrate. While, cultivation of P. tuber-regium in sawdust and sugarcane bagasse resulted in increased contents of K, Na, Ca, and Mg along with highest energy value. On the other hand, rice husk did not support the cultivation of this macrofungus. Therefore, it is of significant interest to initiate the commercial production of this macrofungus so as to fight against the problems of malnutrition found in few African and south Asian countries.

Coffee leaf valorisation into functional wheat flour rusk: their nutritional, physicochemical, and sensory properties.

Coffee leaves are currently emerging as a promising agri-food resource rich in phenolics. This study aims to valorise coffee leaf powder (CLP) by incorporating it in refined wheat flour rusk formulations and analyse its physio-chemical, rheological, functional and sensory characteristics. The progressive replacement of CLP improved the dietary fibre (2.51 ± 0.2%), ash (1.09 ± 0.11%), and water absorption capacity (59.7 ± 0.1%) of the flours. It considerably enhanced the falling number and sedimentation values of the flour blends while decreased the loaf volume. Progressive increase in the dietary phenolics (232.21-435.19 mg/100 g), chlorogenic acid (6.0-7.5 mg/100 g), and ABTS antioxidant activity (963.89-1607.25 µMTEAC/g) of the rusks was observed upon CLP addition. Rusks with 3% CLP were found to have significantly acceptable physical and sensory characteristics. Thus, supplementation of CLP in rusk helps in valorising coffee leaves besides providing a functional bakery product to the coffee industry. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05927-z.

Effect of schedule management plan in project management worth using structural equation modelling.

With the growing digitalization and the need for customers to have more personalized services available, there is a constant need to innovate and fulfil the demands of customers. However, this burden has contributed to further worsening the schedule management for the service companies. Customers now are demanding more personalized service but without having any compromise on the quality and time of delivery. This resulted in creating the need to have a schedule-driven management plan designed. Despite this advantage, there are very limited studies available that even focus on the concept whereas not any study works towards understanding its contribution in affecting project management for service companies. To overcome this, the study aims to assess the perception of 200 employees and 10 managers for understanding a schedule management plan and its impact on project management worth. The employee's perception evaluation via structural equation modelling revealed that there is no direct influence of schedule management on project management worth but via different factors and strategies the influence could be derived. Managers' perceptions validated the findings and provided insight that strategies like the building of a cloud-based platform or predictive modelling should be designed for better schedule management plan development.

Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine.

Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms-it is the acute response in the brain that triggers this cascade of events. Computational modelling of cortical interlaminar and cortico-cortical connectivity and receptor dynamics provide the opportunity to interrogate this question using human electroencephalography (EEG) data recorded during a ketamine infusion. Here, resting-state EEG was recorded in a group of 30 patients with major depressive disorder (MDD) at baseline and during a 0.44 mg/kg ketamine dose comprising a bolus and infusion. Fronto-parietal connectivity was assessed using dynamic causal modelling to fit a thalamocortical model to hierarchically connected nodes in the medial prefrontal cortex and superior parietal lobule. We found a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both parameter changes were correlated across participants with the antidepressant response to ketamine. Changes to the NMDA receptor time constant and inhibitory intraneuronal input into superficial pyramidal cells did not survive correction for multiple comparisons and were not correlated with the antidepressant response. These results provide evidence that the antidepressant effects of ketamine may be mediated by acute fronto-parietal connectivity and GABA receptor dynamics. Furthermore, it supports the large body of literature suggesting the acute mechanism underlying ketamine's antidepressant properties is related to GABA-A and AMPA receptors rather than NMDA receptor antagonism.

Resting-state EEG connectivity recorded before and after rTMS treatment in patients with treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy and tolerability in Major Depressive Disorder (MDD). However, the underlying mechanisms of its antidepressant effects remain unclear. This open-label study investigated electroencephalography (EEG) functional connectivity markers associated with response and the antidepressant effects of rTMS. Resting-state EEG data were collected from 28 participants with MDD before and after a four-week rTMS course. Source-space functional connectivity between 38 cortical regions was compared using an orthogonalised amplitude approach. Depressive symptoms significantly improved following rTMS, with 43 % of participants classified as responders. While the study's functional connectivity findings did not withstand multiple comparison corrections, exploratory analyses suggest an association between theta band connectivity and rTMS treatment mechanisms. Fronto-parietal theta connectivity increased after treatment but did not correlate with antidepressant response. Notably, low baseline theta connectivity was associated with greater response. However, due to the exploratory nature and small sample size, further replication is needed. The findings provide preliminary evidence that EEG functional connectivity, particularly within the theta band, may reflect the mechanisms by which rTMS exerts its therapeutic effects.

From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.

Polyvinylpyrrolidone-Capped Copper Oxide Nanoparticles-Anchored Pramipexole Attenuates the Rotenone-Induced Phenotypes in a Drosophila Parkinson's Disease Model.

Parkinson's disease (PD) is a progressive, age-related neurodegenerative disease. The disease is characterized by the loss of dopaminergic neurons in the substantia nigra, pars compacta of the midbrain. Pramipexole (PPX) is a novel drug used for the treatment of PD. It has a high affinity for the dopamine (DA) D2 receptor subfamily and acts as a targeted mitochondrial antioxidant. It is less effective in the treatment of PD due to its short half-life, highly inconvenient dosing schedule, and long-term side effects. In recent years, PPX-loaded nanoformulations have been actively reported to overcome these limitations. In the current study, we focused on increasing the effectiveness of PPX by minimizing the dosing frequency and improving the treatment strategy for PD. Herein, we report the synthesis of biodegradable polyvinylpyrrolidone (PVP)-capped copper oxide nanoparticles (PVP-CuO NPs), followed by PPX anchoring on the surface of the PVP-CuO NPs (PPX-PVP-CuO NC), in a simple and inexpensive method. The newly formulated PPX-PVP-CuO NC complex was analyzed for its chemical and physical properties. The PPX-PVP-CuO NC was tested to protect against rotenone (RT)-induced toxicity in the Drosophila PD model. The in vivo studies using the RT-induced Drosophila PD model showed significant changes in negative geotaxis behavior and the level of DA and acetylcholinesterase. In addition, oxidative stress markers such as glutathione-S-transferase, total glutathione, thiobarbituric acid reactive species, and protein carbonyl content showed significant amelioration. The positive changes of PPX-PVP-CuO NC treatment in behavior, neurotransmitter level, and antioxidant level suggest its potential role in mitigating the PD phenotype. The formulation can be used for treatment or pharmacological intervention against PD.

Overcoming blinding confounds in psychedelic randomized controlled trials using biomarker driven causal mediation analysis.

INTRODUCTION: There is great interest in the use of psychedelic-assisted therapies to treat a range of mental health conditions and initial randomized controlled trials (RCTs) have generated positive results. However, the effect sizes reported in psychedelic RCTs are likely inflated due to expectancy effects due to the de-blinding of both participants and study personnel to treatment allocation caused by the distinctive psychoactive effects of psychedelic drugs. AREAS COVERED: An introduction to causal inference for RCTs, the underlying assumptions, and potential confounders along with graphical illustrations is provided. It is proposed that causal mediation analysis using objectively measured mediating biomarkers could be used to identify causal pathways between treatment and outcome in psychedelic RCTs, even with de-blinding of participants and give greater confidence as to the mechanistic basis and efficacy of psychedelic therapies. EXPERT OPINION: It is argued that psychedelic therapies should not be approved as licensed medicines until causal pathways are clearly established between treatment and outcome. Potential downsides of doing so include, future indication expansion based on low quality clinical trial evidence, the approval of other therapies based on similarly low-quality evidence, and the potential for efficacy to change over time after approvals has been granted.

Quinoa germ-enriched pasta: Technological, nutritional, textural, and morphological properties.

Germ is the most significant component of quinoa having good nutritional value. Quinoa germ (QG), with balanced amino acid profile and unsaturated fatty acid, is a unique ingredient for human nutrition. In present study, pasta supplemented with QG was characterized for physical, nutritional, morphological, and textural properties. Dough rheology showed increased farinograph water absorption and decreased dough stability with the addition of QG. Addition of QG up to 30% significantly improved the pasta protein content from 13.55% to 20.55%. The substitution of QG to pasta showed decrease in whiteness index and increase in optimum cooking time, swelling index, cooked weight, and cooking loss. It is reported that 20% QG supplement pasta was found to be acceptable; beyond, this level the pasta quality was inferior. Firmness value of pasta significantly increased up to 20% supplementation of QG from 157 to 178 g. The micrographs of pasta with the addition of QG observed increased protein matrix around the starch granules. The results inferred that the QG can serve as a potential functional ingredient for the development of nutritionally enhanced pasta for food industry. PRACTICAL APPLICATION: Quinoa germ (QG) is concentrated source of nutrient with unique nutrition and alternative source of protein. Pasta is the one the popular and fast-growing food in world and explored for enhancement of its nutritional composition to target a larger population with specific nutrient demand. Hence, pasta becomes important vehicle for the supplementation. Developed QG-enriched high-protein pasta will help industry to produce nutritious products at large scale.

Polymer Backbone Stabilized Methylammonium Lead Bromide Perovskite Nano Islands.

Organic-inorganic hybrid perovskite materials continue to attract significant interest due to their optoelectronic application. However, the degradation phenomenon associated with hybrid structures remains a challenging aspect of commercialization. To overcome the stability issue, we have assembled the methylammonium lead bromide nano islands (MNIs) on the backbone of poly-3-dodecyl-thiophene (PDT) for the first time. The structural and morphological properties of the MNI-PDT composite were confirmed with the aid of X-ray diffraction (XRD) studies, Field emission scanning electron microscope (FESEM), and X-ray photoelectron spectroscopy (XPS). The optical properties, namely absorption studies, were carried out by ultraviolet-visible spectroscopy. The fluorescent behavior is determined by photoluminescence (PL) spectroscopy. The emission peak for the MNI-PDT was observed at 536 nm. The morphology studies supported by FESEM indicated that the nano islands are completely covered on the surface of the polymer backbone, making the hybrid (MNI-PDT) stable under environmental conditions for three months. The interfacial interaction strategy developed in the present work will provide a new approach for the stabilization of hybrids for a longer time duration.

Assessment of Odontometric and Osteologic Traits for Gender Determination in South Indians: An Original Research.

In forensic, odontologic, genetic, and anthropological aspects, odontometric and osteologic features have long been a valuable source. The goal of this research was to correlate both the osteologic and odontometric characteristics to determine the most accurate approach for determining gender. A retrospective study involving 1000 adults, with equal gender distribution, was carried out utilizing digital panoramic radiography. The archives were searched for radiographic images of the subjects that were procured for the various procedures that ranged from implantations to rehabilitations. The measurement process was carried out with Image-Pro. There was a noticeable gender difference in the mesodistal breadth, which ranged from 17 to 47. Asymmetry of the lower jaw was considerable in both genders, as was gender variance in osseologic characteristics including ramus diameter and gonial angle. The two groups of attributes exhibited a substantial positive predictive value and thus can be used indetermining gender.

Relationship of Burnout and Extra-Curricular Activities among Dental Students: An Original Research.

Introduction: "Burnout syndrome (BS)" is a work-associated condition which is frequently observed in medical professionals, especially students. Extra-curricular activities (ECAs) are one of the coping techniques that students employ to deal with stress and exhaustion. Goal: The study's goal is to evaluate dental students' levels of burnout and how it correlates with their participation in ECAs. Materials and Procedures: In South India, a dentistry school conducted a cross-sectional questionnaire research with its students. Both the regular and supplemental batches of students from the first year through the fifth year (internship) were included. The "Maslach Burnout Inventory Student Survey", which has 15 items in three areas-"Emotional Fatigue (EE), Cynicism (CY), & Professional Efficacy (PE)"-was used to assess burnout. A 5-point Likert scale was used to grade each response. Poisson log linear model and the Mann-Whitney U test were employed. The threshold for statistical significance was 5 out of 100. Results: Four hundred participants were finalized after the criteria. Over 80% of the participants were women students as in accordance with the routine proportion of the dental students. The participants' average age was 22.1 ± 12 years. Burnout was seen in nearly 20% of subjects. Significant variation was seen for all the three domains of the burnout when they were compared against the ECA (P = 0.019(EE), 0.003(CY), and 0.005(PE)). Conclusion: It is safe to say that among the participants, burnout is a common occurrence. There is a need for early detection of burnout in dental students and prompt, efficient management.

Correction: Study on the utilization of by-products of wheat milling industry for the development of biodegradable plates.

[This corrects the article DOI: 10.1007/s13197-023-05738-8.].

Evaluation of Zn: WO3 Thin Films as a Sensing Layer for Detection of NH3 Gas.

Pristine WO3 and Zn-doped WO3 were synthesized using the spray pyrolysis technique to detect ammonia gas. The prominent orientation of the crystallites along the (200) plane was evident from X-ray diffraction (XRD) studies. Scanning Electron Microscope (SEM) morphology indicated well-defined grains upon Zn doping with a smaller grain size of 62 nm for Zn-doped WO3 (Zn: WO3) film. The photoluminescence (PL) emission at different wavelengths was assigned to defects such as oxygen vacancies, interstitial oxygens, localized defects, etc. X-ray Photoelectron spectroscopy (XPS) studies confirmed the formation of oxygen vacancies in the deposited films. The ammonia (NH3) sensing analysis of the deposited films was carried out at an optimum working temperature of 250 °C. The sensor performance of Zn: WO3 was enhanced compared to pristine WO3 at 1 ppm NH3 concentration, elucidating the possibility of the films in sensing applications.

Study on the utilization of by-products of wheat milling industry for the development of biodegradable plates.

The present study aims at utilizing wheat bran and resultant atta to produce biodegradable-edible plates as an alternative to plastic plates. The edible plates were prepared using different combinations of wheat bran and resultant atta in different ratios viz., WB, 90:10 (WR10); 80:20 (WR20), 70:30 (WR30). Using farinograph, it was observed that the higher the bran higher the water absorption. The doughs from the blends were prepared with water at two different temperatures (100 °C and 27 °C), sheeted, moulded and baked. Plates produced from WR10, 20, 30 were analysed further and based on break test, leak test and sensory WR30 was chosen as the best. WR 30 was found to leak at 23.01 ± 0.24 min with hot water and 85.42 ± 0.11 min with water at room temperature. Moisture, ash, fat, protein, and total dietary fibre content was 4.3 ± 0.016, 4.90 ± 0.08, 3.86 ± 0.075, 16.06 ± 0.082 and 26.92 ± 0.166 respectively. Shelf-life predicted for plate was 250-285 days based on MSI studies done.

Effect of heat treatments on quinoa germ quality and its storage study.

Quinoa is a potential crop to address the situation as it offers a plethora of benefits as it is nutritionally rich and can adapt to extreme climatic and salt conditions. Quinoa germ consists of almost 25-30% of whole grain. Quinoa germ obtained using roller milling has remarkable nutritional properties with high protein, fat and mineral content. Presence higher fat content limits shelf-life of quinoa germ. The objective of the present investigation is to study the effect of different treatment on stabilization of quinoa germ and its storge study. Quinoa germ was subjected to microwave and infrared treatment for shelf-life extension. Colour properties of the germ has not changed drastically by both treatments. Sorption behavior of quinoa germ stored at different RH was studied and results showed typical sigmoid curve for all samples. Sorption studies revealed that treated quinoa germ were stable at 64% RH. The storage study was carried out at accelerated conditions using PET/PE packaging material. Based on the results of the study, it can be inferred that the quinoa germ can be kept up to three months at accelerated conditions. Study demonstrated that microwave treatments of quinoa germ showed highest shelf life of three months at accelerated conditions.

Applicability of Electron Beam Technology for the Degradation of Microcystin-LR in Surface Waters.

Studies were performed to investigate the effects of surface water quality parameters on the degradation of microcystin-LR (MC-LR) using high-energy electron beam (eBeam) technology. Surface water samples were collected across different geographic locations in the United States. Water quality parameters including pH, alkalinity, TDS, and dissolved oxygen were measured in all samples. Degradation of MC-LR in all samples, regardless of parameter concentrations, was above 99%. The effect of natural organic matter (NOM) on MC-LR degradation was also investigated in the presence of fulvic acid. Similarly, the degradation efficiency of MC-LR exceeded 99% for all concentrations of fulvic acid at 5 kGy. This study suggests that surface water quality has a negligible effect on the degradation of MC-LR via eBeam treatment. The results indicate that eBeam technology is a promising technique for the treatment of water contaminated with microcystins.

First report of Fusarium incarnatum associated with fruit rot disease of drumstick (Moringa oleifera L.) in India.

Moringa oleifera Lam. (Moringaceae) is one of the important leafy vegetable trees widely spread from India to Africa and widely used as food and medicine. During field investigation (July, 2021) of drumstick fields in Hiriyur (13°95'79" N; 76°64'45" E), Karnataka, fruits of drumstick plants showed a characteristic rot disease with an incidence ranging from 10-12% in an area of 5 hectares surveyed. Initially water soaked lesions turned to small necrotic lesions and later coalesced to form larger areas covered with white mycelial growth leading to softening and later mummification of fruits. Infected fruits were collected (n=5) and infected fruit parts (margins of healthy and infected tissues) were cut into small pieces, surface sterilized with sodium hypochlorite (2%, v/v) and blotter dried after three sterile water washes. An associated fungal species was isolated on PDA medium amended with Streptomycin (40 mg/L) and incubated at 28 ºC for 1 week. The fungal isolate grown on PDA had dense, white, aerial mycelium with light brown coloration on the reverse side of the agar medium. Morphological characteristics of conidia were determined for single-spore cultures grown on water agar media. Microconidia were single-celled, hyaline, non septate, ovoid, and 8.4 - 9.8 × 1.8 - 2.94 µm (n=20). Macroconidia were three- to five-septate, slightly curved, tapered at the apex, and 24.4 - 28 × 2 - 4 µm (n=20). Based on morphological characters' pathogen was identified as Fusarium sp. (Leslie and Summerell, 2006). Further, three representative isolate (SMG, MYS1 & MYS2) were subjected for molecular identification. The genomic DNA was extracted following CTAB method and ITS-rDNA was amplified using ITS1/ITS4 primers (White et al., 1990) and translation elongation factor (tef-1α) gene was amplified using EF1/EF2 primers (O'Donnell et al., 2009) respectively. ITS-rDNA sequence shared 100% sequence similarity (650bp / 650bp) with reference sequence F. incarnatum (ON226997) followed by 100% sequence identity to F. equiseti (KT277307 & MT953927). But, tef-1α gene sequence analysis in nBLAST showed that the sequence shared 100% (123/123bp) identity with F. incarnatum (F. incarnatum NEAU-TG1 MH920853; M2JP3 OP312673; WEH ON456146). Combined phylogenetic analysis revealed that the isolate shared a common clade with reference sequence of F. incarnatum in the Fusarium-incarnatum-equiseti species complex thus confirming the identity of the isolated pathogen as F. incarnatum (Rob. ex Desm.) Sacc. 1886. The sequences obtained in the present study are deposited in GenBank database (ITS: OP508729, OQ159019, OQ159020 and tef-1α: OP477394, OQ176254, OQ176255). To prove Koch's postulates, pathogenicity test was carried out by inoculating healthy drumstick fruits cv. Bhagya (n=10) with spore suspension (105 conidia/ml). Control fruits (n=5) were sprayed with sterile water. The experiments were conducted in triplicates and repeated twice. Inoculated and control fruits were kept in a moist chamber at 26 ± 2°C for 2 days and observed at regular intervals. Development of disease symptoms were recorded on 52 out of 60 inoculated fruits which were identical with symptoms seen in the field and all control fruits remained symptomless. Identity was confirmed after re-isolation by morphology and culture studies. To the best of our knowledge, this is the first report of F. incarnatum causing a fruit rot of drumstick in India. This disease affected the cost of drumstick production and contributed to the decline in production in India.

The role of social vulnerability in improving interventions for neglected zoonotic diseases: The example of Kyasanur Forest Disease in India.

Forest-based communities manage many risks to health and socio-economic welfare including the increasing threat of emerging zoonoses that are expected to disproportionately affect poor and marginalised groups, and further impair their precarious livelihoods, particularly in Low-and-Middle Income (LMIC) settings. Yet, there is a relative dearth of empirical research on the vulnerability and adaptation pathways of poor and marginalised groups facing emerging zoonoses. Drawing on a survey of 229 households and a series of key-informant interviews in the Western Ghats, we examine the factors affecting vulnerability of smallholder and tribal households to Kyasanur Forest Disease (KFD), an often-fatal tick-borne viral haemorrhagic fever endemic in south India. Specifically, we investigate how different socio-demographic and institutional factors interact to shape KFD vulnerability and the strategies employed by households to adapt to disease consequences. Although surveyed households generally perceived KFD as an important health issue in the study region, there was variability in concern about contracting the disease. Overall results showed that poor access to land (AOR = 0.373, 95% CI: 0.152-0.916), being at or below the poverty line (AOR = 0.253, 95% CI: 0.094-0.685) and being headed by an older person (AOR = 1.038, 95% CI: 1.006-1.071) were all significant determinants of perceived KFD vulnerability. Furthermore, KFD vulnerability is also modulated by important extra-household factors including proximity to private hospitals (AOR = 3.281, 95% CI: 1.220-8.820), main roads (AOR = 2.144, 95% CI: 1.215-3.783) and study location (AOR = 0.226, 95% CI: 0.690-0.743). Our findings highlight how homogenous characterisation of smallholder and tribal communities and the 'techno-oriented' approach of existing interventions may further marginalise the most vulnerable and exacerbate existing inequalities. These findings are important for designing context-specific and appropriate health interventions (including the prioritisation of awareness raising, knowledge networks, livelihood diversification) that enhances the resilience of at-risk social groups within the KFD context. More broadly, our findings highlight how a focus on social vulnerability can help national and international health planners improve health interventions and prioritise among diseases with respect to neglected endemic zoonoses.

Functional connectivity signatures of NMDAR dysfunction in schizophrenia-integrating findings from imaging genetics and pharmaco-fMRI.

Both, pharmacological and genome-wide association studies suggest N-methyl-D-aspartate receptor (NMDAR) dysfunction and excitatory/inhibitory (E/I)-imbalance as a major pathophysiological mechanism of schizophrenia. The identification of shared fMRI brain signatures of genetically and pharmacologically induced NMDAR dysfunction may help to define biomarkers for patient stratification. NMDAR-related genetic and pharmacological effects on functional connectivity were investigated by integrating three different datasets: (A) resting state fMRI data from 146 patients with schizophrenia genotyped for the disease-associated genetic variant rs7191183 of GRIN2A (encoding the NMDAR 2 A subunit) as well as 142 healthy controls. (B) Pharmacological effects of the NMDAR antagonist ketamine and the GABA-A receptor agonist midazolam were obtained from a double-blind, crossover pharmaco-fMRI study in 28 healthy participants. (C) Regional gene expression profiles were estimated using a postmortem whole-brain microarray dataset from six healthy donors. A strong resemblance was observed between the effect of the genetic variant in schizophrenia and the ketamine versus midazolam contrast of connectivity suggestive for an associated E/I-imbalance. This similarity became more pronounced for regions with high density of NMDARs, glutamatergic neurons, and parvalbumin-positive interneurons. From a functional perspective, increased connectivity emerged between striato-pallido-thalamic regions and cortical regions of the auditory-sensory-motor network, while decreased connectivity was observed between auditory (superior temporal gyrus) and visual processing regions (lateral occipital cortex, fusiform gyrus, cuneus). Importantly, these imaging phenotypes were associated with the genetic variant, the differential effect of ketamine versus midazolam and schizophrenia (as compared to healthy controls). Moreover, the genetic variant was associated with language-related negative symptomatology which correlated with disturbed connectivity between the left posterior superior temporal gyrus and the superior lateral occipital cortex. Shared genetic and pharmacological functional connectivity profiles were suggestive of E/I-imbalance and associated with schizophrenia. The identified brain signatures may help to stratify patients with a common molecular disease pathway providing a basis for personalized psychiatry.