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Abstract Insecticidal potential of seven commonly available alkaloids against melon thrips (Thrips palmi Karny) was investigated through in vivo experiments and the bioactivity was explained via in silico approaches. In vivo screening showed highest mortality of T. plami larvae for reserpine (43%), closely followed by tropinone (41%) after 24 h of incubation. After 48 h, tropinone surpassed reserpine with 83% mortality, indicating its prolonged insecticidal activity. A detailed bioassay of tropinone revealed its LC50 values as 1187.9 and 686.9 µg mL−1 after 24 and 48 h, respectively. While studying the molecular interactions between the alkaloids and four physiologically important target proteins of T. palmi, tropinone demonstrated the highest ligand efficiency and lowest predicted inhibitory constant, particularly when forming complexes with CathB protein. However, binding energy calculations of the docked complexes showed most favorable binding of reserpine with CathB. To clear the ambiguity, considering both binding energy and ligand efficiency as the evaluation parameters, a molecular dynamics study was carried out, which predicted higher stability of CathB-tropinone complex than CathB-reserpine complex in terms of the total energy of the system. These in silico findings aligned well with the in vivo results, confirming tropinone as a promising candidate for effective thrips management programs.

Creutzfeldt–Jakob disease (CJD) belongs to the group of fatal neurodegenerative disorders known as prion diseases. We are going to describe the case of a 54-year-old married man who initially presented with rapidly progressive cognitive decline along with behavioral symptoms and was subsequently diagnosed with probable CJD. He presented with 1½ months history of disinhibited behavior, decreased social interaction, persecutory ideas, food refusal, and decreased sleep along with cognitive decline. On examination, the patient had myoclonus and ataxia. Routine blood investigations, serological tests, and autoimmune and paraneoplastic profiles were normal. Injection haloperidol 2.5 mg intramuscular for behavioral symptoms was given with no improvement. The cerebrospinal fluid study revealed positive results for 14-3-3 protein. The patient was diagnosed with probable CJD and subsequently passed away within 1 month of presentation. Thus, CJD should be kept in the differential diagnosis of patients with cognitive decline and persistent behavioral symptoms despite standard psychiatric treatment.

Purpose: Corneal biopsy helps in diagnosing deep-seated or recalcitrant lesions of microbial keratitis (MK). We aim to analyze its role in managing these challenging cases. Methods: This is a retrospective review of 22 cases of corneal biopsy at our institute from January 2010 to December 2021. Data were retrospectively collected using the electronic medical record (EMR) system. Those cases of indolent, progressive MK or deep-seated lesions where cornea scraping was not possible were considered for corneal biopsy to establish the microbiological diagnosis. The primary aims of our study were to analyze the indications, success rates, and outcomes for biopsy patients in our series. Additional outcomes that were analyzed included the average time from presentation to biopsy, the type of causative organism isolated from the biopsy by either histopathological or microbiological method, and the frequency and outcome of surgical interventions performed. Descriptive statistics using mean (±standard deviation) and median (±range) were used to interpret the demographic data. Results: Overall, 15 of 22 patients (68%) had a positive corneal biopsy after microbiological or histopathological examinations. The most identified organism was microsporidia (n = 4,30.7%), followed by mycobacteria (n = 2,15.4%), gram-negative bacilli (n = 2,15.4%), acid-fast bacilli (n = 1,7.6%), fungus (n = 2,15.4%), gram-positive cocci (n = 1,7.6%), and mixed bacterial infection (n = 1,7.6%). Conclusion: Corneal biopsy should be considered a diagnostic modality for patients with deep-seated or unresponsive MK. It can improve the treatment for MK, ensuring targeted therapy.

Abstract Post‐traumatic stress disorder (PTSD) is an anxiety condition caused by exposure to severe trauma. It is characterised by nightmares, flashbacks, hyper‐vigilance and avoidance behaviour. These all lead to impaired functioning reducing quality of life. PTSD affects 2–5% of the population globally. Most sufferers cannot access effective treatment, leading to impaired psychological functioning reducing quality of life. Eye movement desensitisation and reprocessing (EMDR) is a non‐invasive brain stimulation treatment that has shown significant clinical effectiveness in PTSD. Another treatment modality, that is, trauma‐focused cognitive behavioural therapy is also an effective intervention. However, both evidence‐based treatments are significantly resource intensive as they need trained therapists to deliver them. A concept of a neuro‐digital tool for development is proposed to put to clinical practice of delivering EMDR to improve availability, efficiency and effectiveness of treatment. The evidence in using new technologies to measure sleep, geolocation and conversational analysis of social media to report objective outcome measures is explored. If achieved, this can be fed back to users with data anonymously collated to evaluate and improve the tool. Coproduction would be at the heart of product development so that the tool is acceptable and accessible to people with the condition.

Transcranial electrical stimulation (tES) is increasingly recognized for its potential to modulate cerebral blood flow (CBF) and evoke cerebrovascular reactivity (CVR), which are crucial in conditions like mild cognitive impairment (MCI) and dementia. This study explores the impact of tES on the neurovascular unit (NVU), employing a physiological modeling approach to simulate the vascular response to electric fields generated by tES. Utilizing the FitzHugh–Nagumo model for neuroelectrical activity, we demonstrate how tES can initiate vascular responses such as vasoconstriction followed by delayed vasodilation in cerebral arterioles, potentially modulated by a combination of local metabolic demands and autonomic regulation (pivotal locus coeruleus). Here, four distinct pathways within the NVU were modeled to reflect the complex interplay between synaptic activity, astrocytic influences, perivascular potassium dynamics, and smooth muscle cell responses. Modal analysis revealed characteristic dynamics of these pathways, suggesting that oscillatory tES may finely tune the vascular tone by modulating the stiffness and elasticity of blood vessel walls, possibly by also impacting endothelial glycocalyx function. The findings underscore the therapeutic potential vis-à-vis blood-brain barrier safety of tES in modulating neurovascular coupling and cognitive function needing the precise modulation of NVU dynamics. This technology review supports the human-in-the-loop integration of tES leveraging digital health technologies for the personalized management of cerebral blood flow, offering new avenues for treating vascular cognitive disorders. Future studies should aim to optimize tES parameters using computational modeling and validate these models in clinical settings, enhancing the understanding of tES in neurovascular health.

We report observations of the optical counterpart of the long gamma-ray burst (GRB) GRB 230812B and its associated supernova (SN) SN 2023pel. The proximity ( z = 0.36) and high energy ( E _γ _,iso ∼ 10 ^53 erg) make it an important event to study as a probe of the connection between massive star core collapse and relativistic jet formation. With a phenomenological power-law model for the optical afterglow, we find a late-time flattening consistent with the presence of an associated SN. SN 2023pel has an absolute peak r -band magnitude of M _r = −19.46 ± 0.18 mag (about as bright as SN 1998bw) and evolves on quicker timescales. Using a radioactive heating model, we derive a nickel mass powering the SN of M _Ni = 0.38 ± 0.01 M _⊙ and a peak bolometric luminosity of L _bol ∼ 1.3 × 10 ^43 erg s ^−1 . We confirm SN 2023pel’s classification as a broad-line Type Ic SN with a spectrum taken 15.5 days after its peak in the r band and derive a photospheric expansion velocity of v _ph = 11,300 ± 1600 km s ^−1 at that phase. Extrapolating this velocity to the time of maximum light, we derive the ejecta mass M _ej = 1.0 ± 0.6 M _⊙ and kinetic energy ${E}_{\mathrm{KE}}={1.3}_{-1.2}^{+3.3}\times {10}^{51}\,\mathrm{erg}$ . We find that GRB 230812B/SN 2023pel has SN properties that are mostly consistent with the overall GRB-SN population. The lack of correlations found in the GRB-SN population between SN brightness and E _γ _,iso for their associated GRBs across a broad range of 7 orders of magnitude provides further evidence that the central engine powering the relativistic ejecta is not coupled to the SN powering mechanism in GRB-SN systems.

Transcranial Direct Current Stimulation (tDCS) has demonstrated its potential in enhancing surgical training and performance compared to sham tDCS. However, optimizing its efficacy requires the selection of appropriate brain targets informed by neuroimaging and mechanistic understanding. Previous studies have established the feasibility of using portable brain imaging, combining functional near-infrared spectroscopy (fNIRS) with tDCS during Fundamentals of Laparoscopic Surgery (FLS) tasks. This allows concurrent monitoring of cortical activations. Building on these foundations, our study aimed to explore the multi-modal imaging of the brain response using fNIRS and electroencephalogram (EEG) to tDCS targeting the right cerebellar (CER) and left ventrolateral prefrontal cortex (PFC) during a challenging FLS suturing with intracorporeal knot tying task. Involving twelve novices with a medical/premedical background (age: 22–28 years, two males, 10 females with one female with left-hand dominance), our investigation sought mechanistic insights into tDCS effects on brain areas related to error-based learning, a fundamental skill acquisition mechanism. The results revealed that right CER tDCS applied to the posterior lobe elicited a statistically significant (q < 0.05) brain response in bilateral prefrontal areas at the onset of the FLS task, surpassing the response seen with sham tDCS. Additionally, right CER tDCS led to a significant (p < 0.05) improvement in FLS scores compared to sham tDCS. Conversely, the left PFC tDCS did not yield a statistically significant brain response or improvement in FLS performance. In conclusion, right CER tDCS demonstrated the activation of bilateral prefrontal brain areas, providing valuable mechanistic insights into the effects of CER tDCS on FLS peformance. These insights motivate future investigations into the effects of CER tDCS on error-related perception-action coupling through directed functional connectivity studies.

BackgroundMultiple variants of the SARS-CoV-2 virus have plagued the world through successive waves of infection over the past three years. Independent research groups across geographies have shown that the microbiome composition in COVID-19 positive patients (CP) differs from that of COVID-19 negative individuals (CN). However, these observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern.MethodsThe nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at the Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India and subjected to 16s rRNA gene amplicon - based sequencing.FindingsWe found variations in the microbiota of symptomatic vs. asymptomatic COVID-19 patients. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection.InterpretationTo our knowledge, this is the first analytical cross-sectional study of this scale, which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Although no clear signatures were observed, this study shall pave the way for a better understanding of the disease pathophysiology and help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.

Purpose: This study aims to analyze the pattern of follow-ups and the reasons for follow-up loss in keratoplasty cases in a tertiary eye care center. Methods: This is a single-center retrospective cross-sectional study. During the study period, 165 eyes underwent corneal transplantation. The data on the demographic features of the recipients and the indications of keratoplasty, including visual acuity before and after surgery, duration of follow-up, and the condition of the graft at the last follow-up, were collected. The primary outcome was to determine the factors causing lost-to-follow-up (LTFU) among graft recipients. LTFU was defined when a patient failed to adhere to any of the following seven follow-up visits since the surgery: 4 ± 2 weeks, 3 ± 1 months, 6 ± 1 months, 12 ± 2 months, 18 ± 2 months, 24 ± 3 months, and 36 ± 6 months. The secondary outcome was to analyze the best-corrected visual acuity (BCVA) among patients available for the final follow-up. Results: The recipient follow-up rates at 6, 12, 18, 24, and 36 months were 68.5%, 57.6%, 47.9%, 42.4%, and 35.2%, respectively. Old age and distance to the center were significant factors for lost-to-follow-up. A failed graft as an indication for transplantation and those undergoing penetrating keratoplasty for optical purposes were significant factors for completing follow-up. Conclusion: The inability to follow-up after corneal transplantation is a common challenge. Elderly patients and those living in remote areas must be prioritized for follow-ups.

Abstract Error-based learning is one of the basic skill acquisition mechanisms that can be modeled as a perception–action system and investigated based on brain–behavior analysis during skill training. Here, the error-related chain of mental processes is postulated to depend on the skill level leading to a difference in the contextual switching of the brain states on error commission. Therefore, the objective of this paper was to compare error-related brain states, measured with multi-modal portable brain imaging, between experts and novices during the Fundamentals of Laparoscopic Surgery (FLS) “suturing and intracorporeal knot-tying” task (FLS complex task)—the most difficult among the five psychomotor FLS tasks. The multi-modal portable brain imaging combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) for brain–behavior analysis in thirteen right-handed novice medical students and nine expert surgeons. The brain state changes were defined by quasi-stable EEG scalp topography (called microstates) changes using 32-channel EEG data acquired at 250 Hz. Six microstate prototypes were identified from the combined EEG data from experts and novices during the FLS complex task that explained 77.14% of the global variance. Analysis of variance (ANOVA) found that the proportion of the total time spent in different microstates during the 10-s error epoch was significantly affected by the skill level (p

IntroductionOne’s eye movement (in response to visual tasks) provides a unique window into the cognitive processes and higher-order cognitive functions that become adversely affected in cases with cognitive decline, such as those mild cognitive impairment (MCI) and dementia. MCI is a transitional stage between normal aging and dementia.MethodsIn the current work, we have focused on identifying visual tasks (such as horizontal and vertical Pro-saccade, Anti-saccade and Memory Guided Fixation tasks) that can differentiate individuals with MCI and dementia from their cognitively unimpaired healthy aging counterparts based on oculomotor Performance indices. In an attempt to identify the optimal combination of visual tasks that can be used to differentiate the participant groups, clustering was performed using the oculomotor Performance indices.ResultsResults of our study with a group of 60 cognitively unimpaired healthy aging individuals, a group with 60 individuals with MCI and a group with 60 individuals with dementia indicate that the horizontal and vertical Anti-saccade tasks provided the optimal combination that could differentiate individuals with MCI and dementia from their cognitively unimpaired healthy aging counterparts with clustering accuracy of ∼92% based on the saccade latencies. Also, the saccade latencies during both of these Anti-saccade tasks were found to strongly correlate with the Neuropsychological test scores.DiscussionThis suggests that the Anti-saccade tasks can hold promise in clinical practice for professionals working with individuals with MCI and dementia.

Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia occurs when the brain does not receive enough oxygen and blood. A surrogate marker for “intact survival” is necessary for the successful management of HIE. The severity of HIE can be classified based on clinical presentation, including the presence of seizures, using a clinical classification scale called Sarnat staging; however, Sarnat staging is subjective, and the score changes over time. Furthermore, seizures are difficult to detect clinically and are associated with a poor prognosis. Therefore, a tool for continuous monitoring on the cot side is necessary, for example, an electroencephalogram (EEG) that noninvasively measures the electrical activity of the brain from the scalp. Then, multimodal brain imaging, when combined with functional near-infrared spectroscopy (fNIRS), can capture the neurovascular coupling (NVC) status. In this study, we first tested the feasibility of a low-cost EEG-fNIRS imaging system to differentiate between normal, hypoxic, and ictal states in a perinatal ovine hypoxia model. Here, the objective was to evaluate a portable cot-side device and perform autoregressive with extra input (ARX) modeling to capture the perinatal ovine brain states during a simulated HIE injury. So, ARX parameters were tested with a linear classifier using a single differential channel EEG, with varying states of tissue oxygenation detected using fNIRS, to label simulated HIE states in the ovine model. Then, we showed the technical feasibility of the low-cost EEG-fNIRS device and ARX modeling with support vector machine classification for a human HIE case series with and without sepsis. The classifier trained with the ovine hypoxia data labeled ten severe HIE human cases (with and without sepsis) as the “hypoxia” group and the four moderate HIE human cases as the “control” group. Furthermore, we showed the feasibility of experimental modal analysis (EMA) based on the ARX model to investigate the NVC dynamics using EEG-fNIRS joint-imaging data that differentiated six severe HIE human cases without sepsis from four severe HIE human cases with sepsis. In conclusion, our study showed the technical feasibility of EEG-fNIRS imaging, ARX modeling of NVC for HIE classification, and EMA that may provide a biomarker of sepsis effects on the NVC in HIE.

We present optical observations and analysis of the bright type Iax supernova SN 2020udy hosted by NGC 0812. The evolution of the light curve of SN 2020udy is similar to that of other bright type Iax SNe. Analytical modeling of the quasi-bolometric light curves of SN 2020udy suggests that 0.08 ± 0.01 M _⊙ of ^56 Ni would have been synthesized during the explosion. The spectral features of SN 2020udy are similar to those of the bright members of type Iax class, showing a weak Si ii line. The late-time spectral sequence is mostly dominated by iron group elements with broad emission lines. Abundance tomography modeling of the spectral time series of SN 2020udy using TARDIS indicates stratification in the outer ejecta; however, to confirm this, spectral modeling at a very early phase is required. After maximum light, uniform mixing of chemical elements is sufficient to explain the spectral evolution. Unlike in the case of normal type Ia SNe, the photospheric approximation remains robust until +100 days, requiring an additional continuum source. Overall, the observational features of SN 2020udy are consistent with the deflagration of a carbon–oxygen white dwarf.

The study aimed to differentiate experts from novices in laparoscopic surgery tasks using electroencephalogram (EEG) topographic features. A microstate-based common spatial pattern (CSP) analysis with linear discriminant analysis (LDA) was compared to a topography-preserving convolutional neural network (CNN) approach. Expert surgeons (N = 10) and novice medical residents (N = 13) performed laparoscopic suturing tasks, and EEG data from 8 experts and 13 novices were analysed. Microstate-based CSP with LDA revealed distinct spatial patterns in the frontal and parietal cortices for experts, while novices showed frontal cortex involvement. The 3D CNN model (ESNet) demonstrated a superior classification performance (accuracy > 98%, sensitivity 99.30%, specificity 99.70%, F1 score 98.51%, MCC 97.56%) compared to the microstate based CSP analysis with LDA (accuracy ~90%). Combining spatial and temporal information in the 3D CNN model enhanced classifier accuracy and highlighted the importance of the parietal–temporal–occipital association region in differentiating experts and novices.

Abstract Virtual reality (VR) simulator has emerged as a laparoscopic surgical skill training tool that needs validation using brain–behavior analysis. Therefore, brain network and skilled behavior relationship were evaluated using functional near-infrared spectroscopy (fNIRS) from seven experienced right-handed surgeons and six right-handed medical students during the performance of Fundamentals of Laparoscopic Surgery (FLS) pattern of cutting tasks in a physical and a VR simulator. Multiple regression and path analysis (MRPA) found that the FLS performance score was statistically significantly related to the interregional directed functional connectivity from the right prefrontal cortex to the supplementary motor area with F (2, 114) = 9, p

Chronic myeloid leukemia (CML) accounts for 2-3% of childhood leukemias. About 5% of cases present in a blastic phase of CML which clinically and morphologically mimics more common acute leukemias of childhood. We report a case of a 3-yearold male who presented with gradual onset swelling of the abdomen and extremities along with generalized weakness. Examination revealed massive splenomegaly, pallor, and pedal edema. Initial workup showed anemia, thrombocytopenia, and leukocytosis (120,000/uL) with a blast percentage of 35%. Blasts were positive for CD13, CD33, CD117, CD34 and HLA-DR, and stained negative for Myeloperoxidase and Periodic Acid Schiff. Fluorescence in situ hybridization was positive for b3a2/e14a2 junction BCR-ABL1 transcript and negative for RUNX1-RUNX1T1/t(8;21), clinching the diagnosis of CML in myeloid blast crisis. The patient expired within 17 days of diagnosis and initiation of therapy.

We present early-phase panchromatic photometric and spectroscopic coverage spanning the far-ultraviolet to near-infrared regime of the nearest hydrogen-rich core-collapse supernova (SN) in the last 25 yr, SN 2023ixf. We observe early “flash” features in the optical spectra due to confined dense circumstellar material (CSM). We observe high-ionization absorption lines (Fe ii , Mg ii ) in the ultraviolet spectra from very early on. We also observe a multipeaked emission profile of H α in the spectrum beginning at ∼16 days, which indicates ongoing interaction of the SN ejecta with a preexisting shell-shaped CSM having an inner radius of ∼75 au and an outer radius of ∼140 au. The shell-shaped CSM is likely a result of enhanced mass loss ∼35–65 yr before the explosion assuming a standard red supergiant wind. The UV spectra are dominated by multiple highly ionized narrow absorption and broad emission features from elements such as C, N, O, Si, Fe, and Ni. Based on early light-curve models of Type II SNe, we infer that the nearby dense CSM confined to 7 ± 3 × 10 ^14 cm (∼45 au) is a result of enhanced mass loss (10 ^−3.0±0.5 M _⊙ yr ^−1 ) two decades before the explosion.

Introduction. Whilst the coronavirus disease 2019 (COVID-19) vaccination rollout is well underway, there is a concern in Africa where less than 2% of global vaccinations have occurred. In the absence of herd immunity, health promotion remains essential. YouTube has been widely utilised as a source of medical information in previous outbreaks and pandemics. There are limited data on COVID-19 information on YouTube videos, especially in languages widely spoken in Africa. This study investigated the quality and reliability of such videos. Methods. Medical information related to COVID-19 was analysed in 11 languages (English, isiZulu, isiXhosa, Afrikaans, Nigerian Pidgin, Hausa, Twi, Arabic, Amharic, French, and Swahili). Cohen’s Kappa was used to measure inter-rater reliability. A total of 562 videos were analysed. Viewer interaction metrics and video characteristics, source, and content type were collected. Quality was evaluated using the Medical Information Content Index (MICI) scale and reliability was evaluated by the modified DISCERN tool. Results. Kappa coefficient of agreement for all languages was p

Transcranial electrical stimulation (tES) can modulate the neurovascular unit, including the perivascular space morphology, but the mechanisms are unclear. In this perspective article, we used an open-source “rsHRF toolbox” and an open-source functional magnetic resonance imaging (fMRI) transcranial direct current stimulation (tDCS) data set to show the effects of tDCS on the temporal profile of the haemodynamic response function (HRF). We investigated the effects of tDCS in the gray matter and at three regions of interest in the gray matter, namely, the anodal electrode (FC5), cathodal electrode (FP2), and an independent site remote from the electrodes (PZ). A “canonical HRF” with time and dispersion derivatives and a finite impulse response (FIR) model with three parameters captured the effects of anodal tDCS on the temporal profile of the HRF. The FIR model showed tDCS onset effects on the temporal profile of HRF for verum and sham tDCS conditions that were different from the no tDCS condition, which questions the validity of the sham tDCS (placebo). Here, we postulated that the effects of tDCS onset on the temporal profile of HRF are subserved by the effects on neurovascular coupling. We provide our perspective based on previous work on tES effects on the neurovascular unit, including mechanistic grey-box modeling of the effects of tES on the vasculature that can facilitate model predictive control (MPC). Future studies need to investigate grey-box modeling of online effects of tES on the neurovascular unit, including perivascular space, neurometabolic coupling, and neurovascular coupling, that can facilitate MPC of the tES dose-response to address the momentary (“state”) and phenotypic (“trait”) factors.

In developing a Trichoderma viride-based biocontrol program for Fusarium wilt disease in chickpea, the choice of the quality formulation is imperative. In the present study, two types of formulations i.e. powder for seed treatment (TvP) and tablet for direct application (TvT), employing T. viride as the biocontrol agent, were evaluated for their ability to control chickpea wilt under field conditions at three dosages i.e. recommended (RD), double of recommended (DD) and half of recommended (1/2 RD). A screening study for the antagonistic fungi strains based on volatile and non-volatile bioassays revealed that T. viride ITCC 7764 has the most potential among the five strains tested (ITCC 6889, ITCC 7204, ITCC 7764, ITCC 7847, ITCC 8276), which was then used to develop the TvP and TvT formulations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of volatile organic compounds (VOCs) of T. viride strain confirmed the highest abundance of compositions comprising octan-3-one (13.92%), 3-octanol (10.57%), and 1-octen-3-ol (9.40%) in the most potential T. viride 7764. Further Physico-chemical characterization by standard Collaborative International Pesticides Analytical Council (CIPAC) methods revealed the optimized TvP formulation to be free flowing at pH 6.50, with a density of 0.732 g cm-3. The TvT formulation showed a pH value of 7.16 and density of 0.0017 g cm-3 for a complete disintegration time of 22.5 min. The biocontrol potential of TvP formulation was found to be superior to that of TvT formulation in terms of both seed germination and wilt incidence in chickpea under field conditions. However, both the developed formulations (TvP and TvT) expressed greater bioefficacy compared to the synthetic fungicide (Carbendazim 50% WP) and the conventional talc-based formulation. Further research should be carried out on the compatibility of the developed products with other agrochemicals of synthetic or natural origin to develop an integrated disease management (IDM) schedule in chickpea.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain that can be associated with the progression of Alzheimer’s Disease (AD). To address this burden in type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (NCT04626453, NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well tolerated, even during the COVID-19 pandemic. It was also safe, requiring minimal equipment and no supervision. Our paper presents portable near-infrared spectroscopy (NIRS) based measures that showed muscle oxygen saturation (SmO2), i.e., the balance between oxygen delivery and oxygen consumption in muscle, drop during bilateral heel rise task (BHR) and the 6 min walk task (6MWT) significantly (p < 0.05) changed at the post-intervention follow-up from the pre-intervention baseline in the T2DM Intervention group participants. Moreover, post-intervention changes from pre-intervention baseline for the prefrontal activation (both oxyhemoglobin and deoxyhemoglobin) showed statistically significant (p < 0.05, q < 0.05) effect at the right superior frontal gyrus, dorsolateral, during the Mini-Cog task. Here, operational modal analysis provided further insights into the 2-month exercise intervention effects on the very-low-frequency oscillations (p < 0.01) improved in the T2DM Intervention group at post-intervention follow-up from pre-intervention baseline that showed improved aerobic capacity and endurance. Our portable NIRS based measures have practical implications at the point of care for the therapists as they can monitor muscle and brain oxygenation changes during physical and cognitive tests to prescribe personalized physical exercise doses without triggering individual stress response, thereby, enhancing vascular health in T2DM.

Abstract Background Recent studies have indicated an association of gut microbiota and microbial metabolites with type 2 diabetes mellitus (T2D). However, large-scale investigation of the gut microbiota of “prediabetic” (PD) subjects has not been reported. Identifying robust gut microbiome signatures of prediabetes and characterizing early prediabetic stages is important for the understanding of disease development and could be crucial in early diagnosis and prevention. Methods The current study performed amplification and sequencing on the variable regions (V1–V5) of the 16S rRNA genes to profile and compare gut microbiota of prediabetic individuals (N = 262) with normoglycemic individuals (N = 275) from two cohorts in India and Denmark. Similarly, fasting serum inflammatory biomarkers were profiled from the study participants. Results After correcting for strong country-specific cohort effect, 16 operational taxonomic units (OTUs) including members from the genera Prevotella9, Phascolarctobacterium, Barnesiella, Flavonifractor, Tyzzerella_4, Bacteroides, Faecalibacterium, and Agathobacter were identified as enriched in normoglycaemic subjects with respect to the subjects with prediabetes using a negative binomial Wald test. We also identified 144 OTUs enriched in the prediabetic subjects, which included members from the genera Megasphaera, Streptococcus, Prevotella9, Alistipes, Mitsuokella, Escherichia/Shigella, Prevotella2, Vibrio, Lactobacillus, Alloprevotella, Rhodococcus, and Klebsiella. Comparative analyses of relative abundance of bacterial taxa revealed that the Streptococcus, Escherichia/Shigella, Prevotella2, Vibrio, and Alloprevotella OTUs exhibited more than fourfold enrichment in the gut microbiota of prediabetic subjects. When considering subjects from the two geographies separately, we were able to identify additional gut microbiome signatures of prediabetes. The study reports a probable association of Megasphaera OTU(s) with impaired glucose tolerance, which is significantly pronounced in Indian subjects. While the overall results confirm a state of proinflammation as early as in prediabetes, the Indian cohort exhibited a characteristic pattern of abundance of inflammatory markers indicating low-grade intestinal inflammation at an overall population level, irrespective of glycemic status. Conclusions The results present trans-ethnic gut microbiome and inflammation signatures associated with prediabetes, in Indian and Danish populations. The identified associations may be explored further as potential early indicators for individuals at risk of dysglycemia.

Abstract Background Type 2 diabetes (T2D), a multifactorial disease influenced by host genetics and environmental factors, is the most common endocrine disease. Several studies have shown that the gut microbiota as a close-up environmental mediator influences host physiology including metabolism. The aim of the present study is to examine the compositional and functional potential of the gut microbiota across individuals from Denmark and South India with a focus on T2D. Many earlier studies have investigated the microbiome aspects of T2D, and it has also been anticipated that such microbial associations would be dependent on diet and ethnic origin. However, there has been no large scale trans-ethnic microbiome study earlier in this direction aimed at evaluating any “universal” microbiome signature of T2D. Methods 16S ribosomal RNA gene amplicon sequencing was performed on stool samples from 279 Danish and 294 Indian study participants. Any differences between the gut microbiota of both populations were explored using diversity measures and negative binomial Wald tests. Study samples were stratified to discover global and country-specific microbial signatures for T2D and treatment with the anti-hyperglycemic drug, metformin. To identify taxonomical and functional signatures of the gut microbiota for T2D and metformin treatment, we used alpha and beta diversity measures and differential abundances analysis, comparing metformin-naive T2D patients, metformin-treated T2D patients, and normoglycemic individuals. Results Overall, the gut microbial communities of Danes and Indians are compositionally very different. By analyzing the combined study materials, we identify microbial taxonomic and functional signatures for T2D and metformin treatment. T2D patients have an increased relative abundance of two operational taxonomic units (OTUs) from the Lachnospiraceae family, and a decreased abundance of Subdoligranulum and Butyricicoccus. Studying each population per se, we identified T2D-related microbial changes at the taxonomic level within the Danish population only. Alpha diversity indices show that there is no significant difference between normoglycemic individuals and metformin-naive T2D patients, whereas microbial richness is significantly decreased in metformin-treated T2D patients compared to metformin-naive T2D patients and normoglycemic individuals. Enrichment of two OTUs from Bacteroides and depletion of Faecalibacterium constitute a trans-ethnic signature of metformin treatment. Conclusions We demonstrate major compositional differences of the gut microbiota between Danish and South Indian individuals, some of which may relate to differences in ethnicity, lifestyle, and demography. By comparing metformin-naive T2D patients and normoglycemic individuals, we identify T2D-related microbiota changes in the Danish and Indian study samples. In the present trans-ethnic study, we confirm that metformin changes the taxonomic profile and functional potential of the gut microbiota.

Abstract Background Investigation of lobule-specific electric field effects of cerebellar transcranial direct current stimulation (ctDCS) on overground gait performance has not been performed, so this study aimed to investigate the feasibility of two lobule-specific bilateral ctDCS montages to facilitate overground walking in chronic stroke. Methods Ten chronic post-stroke male subjects participated in this repeated-measure single-blind crossover study, where we evaluated the single-session effects of two bilateral ctDCS montages that applied 2 mA via 3.14 cm2 disc electrodes for 15 min targeting (a) dentate nuclei (also, anterior and posterior lobes), and (b) lower-limb representations (lobules VIIb-IX). A two-sided Wilcoxon rank-sum test was performed at a 5% significance level on the percent normalized change measures in the overground gait performance. Partial least squares regression (PLSR) analysis was performed on the quantitative gait parameters as response variables to the mean lobular electric field strength as the predictors. Clinical assessments were performed with the Ten-Meter walk test (TMWT), Timed Up & Go (TUG), and the Berg Balance Scale based on minimal clinically important differences (MCID). Results The ctDCS montage specific effect was found significant using a two-sided Wilcoxon rank-sum test at a 5% significance level for 'Step Time Affected Leg' (p = 0.0257) and '%Stance Time Unaffected Leg' (p = 0.0376). The changes in the quantitative gait parameters were found to be correlated to the mean electric field strength in the lobules based on PLSR analysis (R 2 statistic = 0.6574). Here, the mean electric field strength at the cerebellar lobules, Vermis VIIIb, Ipsi-lesional IX, Vermis IX, Ipsi-lesional X, had the most loading and were positively related to the 'Step Time Affected Leg' and '%Stance Time Unaffected Leg,' and negatively related to the '%Swing Time Unaffected Leg,' '%Single Support Time Affected Leg.' Clinical assessments found similar improvement in the TMWT (MCID: 0.10 m/s), TUG (MCID: 8 s), and BBS score (MCID: 12.5 points) for both the ctDCS montages. Conclusion Our feasibility study found an association between the lobular mean electric field strength and the changes in the quantitative gait parameters following a single ctDCS session in chronic stroke. Both the ctDCS montages improved the clinical outcome measures that should be investigated with a larger sample size for clinical validation. Trial registration: Being retrospectively registered.

Abstract Embroidery through computer aided semi-automatic machines is one of the most widely used option for the surface ornamentation of apparel fabrics at present. Since the embroidery process includes addition of certain amount of embroidery-threads depending upon the design motif, it is quite obvious that basic physical and functional properties of fabric are subject to change. It is therefore important to develop an algorithm or empirical equation for proper prediction of the properties of the embroidered fabric, relevant to its required end-use in apparel industry. In this context, an effort has been made to determine a prediction equation through linear multiple regressions for the prediction of longitudinal stiffness of embroidered fabric in terms of flexural rigidity in warp direction of the base fabric, considering the input parameters as warp-way flexural rigidity of the base fabric, breaking load and linear density of the embroidery thread, stitch density, average stitch length and average stitch angle of the embroidery design. The final Prediction model is statistically verified taking new embroidery samples of different varieties. It is found that the model can predict with a very satisfactory level of accuracy. Also, the influences of the embroidery parameters in this context have been analyzed through the corresponding regression coefficients and the three dimensional (3D) surface curves. Stitch density has been emerged as the most influential parameter, followed by the stitch length and the stitch angle.

Following the extraction of essential oil, citrus (Mousambi, Kinnow, and Orange) peel wastes were used to produce pectin. The yield of essential oil and pectin was maximum in orange. Pectin was characterized by Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectroscopy. The degree of esterification (DE) and methoxyl content (MC) was maximum in orange whereas, the equivalent weight was maximum in Mousambi. A significant increase (61.8%) in the Lactobacillus fermentum population was observed with pectin as compared with sugar. Three sources followed the Orange > Kinnow > Mousambi trend as a prebiotic source. It was attributed to higher DE as well as higher MC. Enhancement in the bacterial population was in the range of 79.16–87.50%. The present work confirms the potential of pectin as a probiotic source for the enhancement of the bacterial population. Thus, it has a large scope for use in the food industry targeting a circular economy.

The present study aimed to develop nanoemulsions (NEs) of essential oil (EO) and lipid-soluble extract (HE) of Pogostemon cablin leaves using biosurfactant, saponin. Hydro-distilled EO and fat-soluble HE were analyzed using GC-MS, which revealed 38.7 ± 2.7% and 37.5 ± 2.1% patchoulol, respectively. EO and HE were formulated with saponin to prepare corresponding coarse emulsions (CEs); furthermore, high-speed homogenization for 2 min was followed by ultrasonication for 3 min with constant frequency of 50 kHz. of the CEs resulted in respective NEs. NEs were characterized for the physico-chemical properties such as emulsion intrinsic stability, particle size distribution, polydispersity index (PDI), and transmission electron microscopy (TEM) for morphology and accurate nanodroplet diameters. CEs and NEs were investigated for insecticidal efficacy against adults of Tetranychus urticae and larvae of Spodoptera litura. Stable NEs of EO and HE at 500 μg mL−1 concentration exhibited corresponding average particle size of 51.7 and 89.9 nm, while TEM image revealed spherical-shaped droplets with the average droplet diameters of 15.3 and 29.4 nm, respectively. NEs of EO and HE displayed highest efficacy in contact toxicity (LC50 43.2 and 58.4 μg mL−1) after 48 h and fumigant toxicity (LC50 9.3 and 13.6 μg mL−1) after 24 h against T. urticae. In addition, NEs of EO showed considerable antifeedant and feeding deterrent action (AI 99.21 ± 0.74 and FI 99.73 ± 1.24) against S. litura larvae.

Modified starch based composites were prepared with bentonite/organobentonite for their potential use as carriers for pesticide delivery. Soluble starch was esterified with dicarboxylic acid chlorides. Mean degree of substitution of modified starches varied from 0.101 to 0.353. Composites were prepared by solution intercalation method using these esterified starches and bentonite or cetyltrimethylammonium bentonite as filler materials. TEM analysis of composites showed well exfoliated/intercalated structures. Atrazine as a model pesticide was encapsulated in them and encapsulation was found to be 83.52–92.83%. These composites were also found to be acted as controlled release matrices for atrazine and release pattern was diffusion controlled. As compared to the commercially available wettable powder formulation, the composites were able to release encapsulated atrazine in water for a longer period. The research showed that the prepared composites could be further investigated as carriers for controlled release formulations of pesticides to minimize dose and number of applications.

Crude oil contamination of soil and water resources is a widespread issue. The present study evaluated the degradation of aliphatic hydrocarbons (C11–C36) in crude oil by 17 bacteria isolated from a crude oil–contaminated soil. The results suggested that Pseudomonas sp. and Bacillus amyloliquefaciens were the best hydrocarbon-degrading bacteria in the presence of surfactant Tween-80 (0.1% w/v). Based on the present investigation and a previous study, Pseudomonas sp. + B. amyloliquefaciens and fungus Aspergillus sydowii were identified as best oil degraders and were immobilized in alginate–bentonite beads, guargum–nanobenonite water dispersible granules (WDGs), and carboxy methyl cellulose (CMC)–bentonite composite. Sandy loam soil was fortified with 1, 2, and 5% crude oil, and total petroleum hydrocarbon (TPH) degradation efficiency of free cultures and bio-formulations was evaluated in sandy loam soils. Compared to a half-life (t1/2) of 69.7 days in the control soil (1% oil), free cultures of Pseudomonas sp. + B. amyloliquefaciens and A. sydowii degraded TPH with t1/2 of 10.8 and 19.4 days, respectively. Increasing the oil content slowed down degradation, and the t1/2 in the control and soils inoculated with Pseudomonas sp. + B. amyloliquefaciens and A. sydowii was 72.9, 14.7, and 22.2 days (2%) and 87.0, 23.4, and 30.8 days (5%), respectively. Supplementing soil with ammonium sulfate (1%) enhanced TPH degradation by Pseudomonas sp. + B. amyloliquefaciens (t1/2–10 days) and A. sydowii (t1/2–12.7 days). All three bio-formulations were effective in degrading TPH (1%), and the t1/2 was 10.7–11.9 days (Pseudomonas sp. + B. amyloliquefaciens and 14–20.2 days (A. sydowii) and were at par with free cultures. Microbial diversity analysis based on taxonomic markers and functional markers suggested that the bioaugmentation process helped keep soil in the active stage and restored the original microbial population to some extent. The present study concluded that bio-formulations of crude oil–degrading microbes can be exploited for its degradation in the contaminated environment.

Gut health is intimately linked to dietary habits and the microbial community (microbiota) that flourishes within. The delicate dependency of the latter on nutritional availability is also strongly influenced by interactions (such as, parasitic or mutualistic) between the resident microbes, often affecting their growth rate and ability to produce key metabolites. Since, cultivating the entire repertoire of gut microbes is a challenging task, metabolic models (genome-based metabolic reconstructions) could be employed to predict their growth patterns and interactions. Here, we have used 803 gut microbial metabolic models from the Virtual Metabolic Human repository, and subsequently optimized and simulated them to grow on 13 dietary compositions. The presented pairwise interaction data (https://osf.io/ay8bq/) and the associated bacterial growth rates are expected to be useful for (a) deducing microbial association patterns, (b) diet-based inference of personalised gut profiles, and (c) as a steppingstone for studying multi-species metabolic interactions.

We present optical, near-infrared, and radio observations of supernova (SN) SN IIb 2022crv. We show that it retained a very thin H envelope and transitioned from an SN IIb to an SN Ib; prominent H α seen in the pre-maximum phase diminishes toward the post-maximum phase, while He i lines show increasing strength. SYNAPPS modeling of the early spectra of SN 2022crv suggests that the absorption feature at 6200 Å is explained by a substantial contribution of H α together with Si ii , as is also supported by the velocity evolution of H α . The light-curve evolution is consistent with the canonical stripped-envelope SN subclass but among the slowest. The light curve lacks the initial cooling phase and shows a bright main peak (peak M _V = −17.82 ± 0.17 mag), mostly driven by radioactive decay of ^56 Ni. The light-curve analysis suggests a thin outer H envelope ( M _env ∼ 0.05 M _⊙ ) and a compact progenitor ( R _env ∼ 3 R _⊙ ). An interaction-powered synchrotron self-absorption model can reproduce the radio light curves with a mean shock velocity of 0.1 c . The mass-loss rate is estimated to be in the range of (1.9−2.8) × 10 ^−5 M _⊙ yr ^−1 for an assumed wind velocity of 1000 km s ^−1 , which is on the high end in comparison with other compact SNe IIb/Ib. SN 2022crv fills a previously unoccupied parameter space of a very compact progenitor, representing a beautiful continuity between the compact and extended progenitor scenario of SNe IIb/Ib.

We present a broadband X-ray study (∼0.3–50 keV) of the dwarf nova SS Cyg highlighting the changes in the accretion during two phases, the quiescence and the outburst states. The investigation was based on simultaneous observations carried out with the XMM-Newton and NuSTAR telescopes in two epochs, involving medium- and high-resolution spectroscopy. Spectra were harder during quiescence ( kT _high ∼ 22.8 keV) than the outburst ( kT _high ∼ 8.4 keV), while the mass accretion rate increased by ∼35 times in the outburst (1.7 × 10 ^16 g s ^−1 ) as compared to quiescence. The bolometric luminosity (0.01–100.0 keV) during the outburst was dominated by a blackbody emission ( kT _BB ∼ 28 eV) from the optically thick boundary layer (BL), and the inner edge of the accretion disk resides very close to the white-dwarf (WD) surface. X-rays from the BL are consistent with the WD having mass ${1.18}_{-0.01}^{+0.02}\,{M}_{\odot }$ . Our study conclusively confirms the presence of the reflection hump in the 10–30 keV range for both phases, which arises when X-ray photons hit colder material and undergo Compton scattering. We estimated a similarly strong reflection amplitude during quiescence (∼1.25) and the outburst (∼1.31), indicating both the WD surface and disk are contributing to reflection. The neutral Fe K _α line, which is correlated with Compton reflection, also showed similar strength (∼80 eV) in both phases. Finally, X-rays also revealed the presence of a partial intrinsic absorber during the outburst, possibly due to an outflowing accretion disk wind.

We present the optical photometric and spectroscopic analysis of two Type Iax supernovae (SNe), 2018cni and 2020kyg. SN 2018cni is a bright Type Iax SN ( M _V _,peak = −17.81 ± 0.21 mag), whereas SN 2020kyg ( M _V _,peak = −14.52 ± 0.21 mag) is a faint one. We derive ^56 Ni mass of 0.07 and 0.002 M _⊙ and ejecta mass of 0.48 and 0.14 M _⊙ for SNe 2018cni and 2020kyg, respectively. A combined study of the bright and faint Type Iax SNe in R / r -band reveals that the brighter objects tend to have a longer rise time. However, the correlation between the peak luminosity and decline rate shows that bright and faint Type Iax SNe exhibit distinct behavior. Comparison with standard deflagration models suggests that SN 2018cni is consistent with the deflagration of a CO white dwarf, whereas the properties of SN 2020kyg can be better explained by the deflagration of a hybrid CONe white dwarf. The spectral features of both the SNe point to the presence of similar chemical species but with different mass fractions. Our spectral modeling indicates stratification at the outer layers and mixed inner ejecta for both of the SNe.

Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response; however, the mechanisms have not been investigated systematically using systems biology approaches. Our study presents a grey-box linear model that was developed from a physiologically detailed multi-compartmental neurovascular unit model consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. Then, model linearization was performed on the physiologically detailed nonlinear model to find appropriate complexity (Akaike information criterion) to fit functional near-infrared spectroscopy (fNIRS) based measure of blood volume changes, called cerebrovascular reactivity (CVR), to high-definition (HD) tDCS. The grey-box linear model was applied on the fNIRS-based CVR during the first 150 seconds of anodal HD-tDCS in eleven healthy humans. The grey-box linear models for each of the four nested pathways starting from tDCS scalp current density that perturbed synaptic potassium released from active neurons for Pathway 1, astrocytic transmembrane current for Pathway 2, perivascular potassium concentration for Pathway 3, and voltage-gated ion channel current on the smooth muscle cell for Pathway 4 were fitted to the total hemoglobin concentration (tHb) changes from optodes in the vicinity of 4x1 HD-tDCS electrodes as well as on the contralateral sensorimotor cortex. We found that the tDCS perturbation Pathway 3 presented the least mean square error (MSE, median

Individual differences in the responsiveness of the brain to transcranial electrical stimulation (tES) are increasingly demonstrated by the large variability in the effects of tES. Anatomically detailed computational brain models have been developed to address this variability; however, static brain models are not “realistic” in accounting for the dynamic state of the brain. Therefore, human-in-the-loop optimization at the point of care is proposed in this perspective article based on systems analysis of the neurovascular effects of tES. First, modal analysis was conducted using a physiologically detailed neurovascular model that found stable modes in the 0 Hz to 0.05 Hz range for the pathway for vessel response through the smooth muscle cells, measured with functional near-infrared spectroscopy (fNIRS). During tES, the transient sensations can have arousal effects on the hemodynamics, so we present a healthy case series for black-box modeling of fNIRS–pupillometry of short-duration tDCS effects. The block exogeneity test rejected the claim that tDCS is not a one-step Granger cause of the fNIRS total hemoglobin changes (HbT) and pupil dilation changes (p < 0.05). Moreover, grey-box modeling using fNIRS of the tDCS effects in chronic stroke showed the HbT response to be significantly different (paired-samples t-test, p < 0.05) between the ipsilesional and contralesional hemispheres for primary motor cortex tDCS and cerebellar tDCS, which was subserved by the smooth muscle cells. Here, our opinion is that various physiological pathways subserving the effects of tES can lead to state–trait variability, which can be challenging for clinical translation. Therefore, we conducted a case study on human-in-the-loop optimization using our reduced-dimensions model and a stochastic, derivative-free covariance matrix adaptation evolution strategy. We conclude from our computational analysis that human-in-the-loop optimization of the effects of tES at the point of care merits investigation in future studies for reducing inter-subject and intra-subject variability in neuromodulation.

Environmental concerns related to synthetic pesticides and the emphasis on the adoption of an integrated pest management concept as a cardinal principle have strengthened the focus of global research and development on botanical pesticides. A scientific understanding of the mode of action of biomolecules over a range of pests is key to the successful development of biopesticides. The present investigation focuses on the in silico protein-ligand interactions of allyl isothiocyanate (AITC), a major constituent of black mustard (Brassica nigra) essential oil (MEO) against two pests, namely, Meloidogyne incognita (Mi) and Fusarium oxysporum f. sp. lycopersici (Fol), that cause severe yield losses in agricultural crops, especially in vegetables. The in vitro bioassay results of MEO against Mi exhibited an exposure time dependent on the lethal concentration causing 50% mortality (LC50) values of 47.7, 30.3, and 20.4 μg ml−1 at 24, 48, and 72 h of exposure, respectively. The study revealed short-term nematostatic activity at lower concentrations, with nematicidal activity at higher concentrations upon prolonged exposure. Black mustard essential oil displayed excellent in vitro Fol mycelial growth inhibition, with an effective concentration to cause 50% inhibition (EC50) value of 6.42 μg ml−1. In order to decipher the mechanism of action of MEO, its major component, AITC (87.6%), which was identified by gas chromatography–mass spectrometry (GC-MS), was subjected to in silico docking and simulation studies against seven and eight putative target proteins of Mi and Fol, respectively. Allyl isothiocyanate exhibited the highest binding affinity with the binding sites of acetyl cholinesterase (AChE), followed by odorant response gene-1 (ODR1) and neuropeptide G-protein coupled receptor (nGPCR) in Mi, suggesting the possible suppression of neurotransmission and chemosensing functions. Among the target proteins of Fol, AITC was the most effective protein in blocking chitin synthase (CS), followed by 2,3-dihydroxy benzoic acid decarboxylase (6m53) and trypsinase (1try), thus inferring these as the principal molecular targets of fungal growth. Taken together, the study establishes the potential of MEO as a novel biopesticide lead, which will be utilized further to manage the Mi–Fol disease complex.

The ability of chaperonins to buffer mutations that affect protein folding pathways suggests that their abundance should be evolutionarily advantageous. Here, we investigate the effect of chaperonin overproduction on cellular fitness in Escherichia coli. We demonstrate that chaperonin abundance confers 1) an ability to tolerate higher temperatures, 2) improved cellular fitness, and 3) enhanced folding of metabolic enzymes, which is expected to lead to enhanced energy harvesting potential.

Abstract Background Stroke-related sensory and motor deficits often steal away the independent mobility and balance from stroke survivors. Often, this compels the stroke survivors to rely heavily on their non-paretic leg during weight shifting to execute activities of daily living (ADL), with reduced usage of the paretic leg. Increased reliance on non-paretic leg often leads to learned nonuse of the paretic leg. Therefore, it is necessary to measure the contribution of individual legs toward one’s overall balance. In turn, techniques can be developed to condition the usage of both the legs during one’s balance training, thereby encouraging the hemiplegic patients for increased use of their paretic leg. The aim of this study is to (1) develop a virtual reality (VR)-based balance training platform that can estimate the contribution of each leg during VR-based weight-shifting tasks in an individualized manner and (2) understand the implication of operant conditioning paradigm during balance training on the overall balance of hemiplegic stroke patients. Result Twenty-nine hemiplegic patients participated in a single session of VR-based balance training. The participants maneuvered virtual objects in the virtual environment using two Wii Balance Boards that measured displacement in the center of pressure (CoP) due to each leg when one performed weight-shifting tasks. For operant conditioning, the weight distribution across both the legs was conditioned (during normal trial) to reward participants for increased usage of the paretic leg during the weight-shifting task. The participants were offered multiple levels of normal trials with intermediate catch trial (with equal weight distribution between both legs) in an individualized manner. The effect of operant conditioning during the normal trials was measured in the following catch trials. The participants showed significantly improved performance in the final catch trial compared to their initial catch trial task. Also, the enhancement in CoP displacement of the paretic leg was significant in the final catch trial compared to the initial catch trial. Conclusion The developed system was able to encourage participants for improved usage of their paretic leg during weight-shifting tasks. Such an approach has the potential to address the issue of learned nonuse of the paretic leg in stroke patients.

Acquisition of fine motor skills is a time-consuming process as it is based on learning via frequent repetitions. Transcranial electrical stimulation (tES) is a promising means of enhancing simple motor skill development via neuromodulatory mechanisms. Here, we report that non-invasive neurostimulation facilitates the learning of complex fine bimanual motor skills associated with a surgical task. During the training of 12 medical students on the Fundamentals of Laparoscopic Surgery (FLS) pattern cutting task over a period of 12 days, we observed that transcranial direct current stimulation (tDCS) decreased error level and the variability in performance, compared to the Sham group. Furthermore, by concurrently monitoring the cortical activations of the subjects via functional near-infrared spectroscopy (fNIRS), our study showed that the cortical activation patterns were significantly different between the tDCS and Sham group, with the activation of primary motor cortex (M1) and prefrontal cortex (PFC) contralateral to the anodal electrode significantly decreased while supplemental motor area (SMA) increased by tDCS. The lowered performance errors were retained after 1-month post-training. This work supports the use of tDCS to enhance performance accuracy in fine bimanual motor tasks.

Nematicidal potential of essential oils (EOs) has been widely reported. Terpenoids present in most of the essential oils have been reported responsible for their bioactivity though very less is known about their modes of action. In the present study, an in vitro screening of nine Eos, namely, Citrus sinensis (OEO), Myrtus communis (MTEO), Eucalyptus citriodora (CEO), Melaleuca alternifolia (TEO), Acorus calamus (AEO), Commiphora myrrha (MREO), Cymbopogon nardus (CNEO), Artemisia absinthium (WEO), and Pogostemon cablin (PEO) against Meloidogyne incognita revealed OEO, CNEO, and TEO as most effective with LC50 39.37, 43.22, and 76.28 μg ml–1 respectively. EOs had varying compositions of mono- and sesquiterpenes determined by gas chromatography-mass spectrometry (GC-MS) analysis. The in silico molecular interactions screening of major EO constituents and the seven selected target proteins of the nematode indicated highest binding affinity of geraniol-ODR1 (odorant response gene 1) complex (ΔG = -36.9 kcal mol–1), due to extensive H-bonding, hydrophobic and π-alkyl interactions. The relative binding affinity followed the order: geraniol-ODR1 > β-terpineol-ODR1 > citronellal-ODR1 > l-limonene-ODR1 > γ-terpinene-ODR1. Taken together, the cumulative in vitro and computational bioefficacy analysis related to the chemoprofiles of EOs provides useful leads on harnessing the potential of EOs as bionematicides. The insight on biochemical ligand–target protein interactions described in the present work will be helpful in logical selection of biomolecules and essential oils for development of practically viable bionematicidal products.

Background: Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on a competing neurobehavioral decision systems model. The next objective was to develop the theory by conducting a computational simulation of NIBS of the cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD)-related dysfunctional “cue-reactivity”—a construct closely related to “craving”—that is a core symptom. Our third objective was to test the feasibility of a neuroimaging-guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) metrics of sensorimotor gating. Therefore, we conducted a computational simulation of NIBS, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) of the cerebellar cortex and deep cerebellar nuclei (DCN) of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging-guided NIBS approach for the cerebellar lobule (VII) and prefrontal cortex based on a healthy human study. Results: Simulation of cerebellar tDCS induced gamma oscillations in the cerebral cortex, while transcranial temporal interference stimulation induced a gamma-to-beta frequency shift. A preliminary healthy human study (N = 10) found that 2 mA cerebellar tDCS evoked similar oxyhemoglobin (HbO) response in the range of 5 × 10−6 M across the cerebellum and PFC brain regions (α = 0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO-driven phase–amplitude-coupled (PAC; 4 Hz, ±2 mA (max)) cerebellar tACS evoked HbO levels in the range of 10−7 M that were statistically different (α = 0.01) across these brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC and closed-loop fNIRS-driven ctACS at 4 Hz, which may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging for closed-loop NIBS during operant conditioning.

Brucellosis is a well-known and wide spread zoonotic disease. It is endemic in several parts of Asia, including India. In this study, seroprevalence of porcine brucellosis was studied among apparently healthy pigs in Meghalaya where pig keeping plays a significant function in socio-economic development. Serum samples (3,597) from pigs were screened using Rose Bengal Plate Test (RBPT) and indirect ELISA. Isolation of Brucella was attempted in clinical samples. A total of 13 (0.36%) were positive by RBPT and 72(2%) by Indirect ELISA. Brucella suis isolate was recovered from placenta of an aborted pig. Risk factors involved in the transmission of brucellosis amongst swine herd were studied. It was observed that age (OR=0.590; P=0.04) and sex (OR=0.557; P=0.04) were significant intrinsic risk factors for transmission of porcine brucellosis. Although the seroprevalence is low, isolation of B. suis from an aborted pig indicated that disease is actively circulating among swine herds of Meghalaya.

Abstract Background Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M. tuberculosis proteins, (ii) gene regulatory network pertaining to adaptation of M. tuberculosis to hypoxia and (iii) alterations in M. tuberculosis metabolism under hypoxic condition. Subsequently, cross-talks between these components have been probed to evaluate possible gene-regulatory events as well as HPIs which are likely to drive metabolic changes during pathogen’s adaptation to the intra-host hypoxic environment. Results The newly identified HPIs suggest the pathogen’s ability to subvert host mediated reactive oxygen intermediates/ reactive nitrogen intermediates (ROI/ RNI) stress as well as their potential role in modulating host cell cycle and cytoskeleton structure. The results also indicate a significantly pronounced effect of HPIs on hypoxic metabolism of M. tuberculosis. Findings from the current study underscore the necessity of investigating the infection process from a systems-level perspective incorporating different facets of intra-cellular survival of the pathogen. Conclusions The comprehensive host-pathogen interaction network, a Boolean model of M. tuberculosis H37Rv (Mtb) hypoxic gene-regulation, as well as a genome scale metabolic model of Mtb, built for this study are expected to be useful resources for future studies on tuberculosis infection.

Surgical skill acquisition may be facilitated with a safe application of transcranial direct current stimulation (tDCS). A preliminary meta-analysis of randomized control trials showed that tDCS was associated with significantly better improvement in surgical performance than the sham control; however, meta-analysis does not address the mechanistic understanding. It is known from skill learning studies that the hierarchy of cognitive control shows a rostrocaudal axis in the frontal lobe where a shift from posterior to anterior is postulated to mediate progressively abstract, higher-order control. Therefore, optimizing the transcranial electrical stimulation to target surgical task-related brain activation at different stages of motor learning may provide the causal link to the learning behavior. This comment paper presents the computational approach for neuroimaging guided tDCS based on open-source software pipelines and an open-data of functional near-infrared spectroscopy (fNIRS) for complex motor tasks. We performed an fNIRS-based cortical activation analysis using AtlasViewer software that was used as the target for tDCS of the motor complexity-related brain regions using ROAST software. For future studies on surgical skill training, it is postulated that the higher complexity laparoscopic suturing with intracorporeal knot tying task may result in more robust activation of the motor complexity-related brain areas when compared to the lower complexity laparoscopic tasks.