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Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Climate change across the globe has an impact on the occurrence, prevalence, and severity of plant diseases. About 30% of yield losses in major crops are due to plant diseases; emerging diseases are likely to worsen the sustainable production in the coming years. Plant diseases have led to increased hunger and mass migration of human populations in the past, thus a serious threat to global food security. Equipping the modern varieties/hybrids with enhanced genetic resistance is the most economic, sustainable and environmentally friendly solution. Plant geneticists have done tremendous work in identifying stable resistance in primary genepools and many times other than primary genepools to breed resistant varieties in different major crops. Over the last two decades, the availability of crop and pathogen genomes due to advances in next generation sequencing technologies improved our understanding of trait genetics using different approaches. Genome-wide association studies have been effectively used to identify candidate genes and map loci associated with different diseases in crop plants. In this review, we highlight successful examples for the discovery of resistance genes to many important diseases. In addition, major developments in association studies, statistical models and bioinformatic tools that improve the power, resolution and the efficiency of identifying marker-trait associations. Overall this review provides comprehensive insights into the two decades of advances in GWAS studies and discusses the challenges and opportunities this research area provides for breeding resistant varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gangurde, Xavier, Naik, Jha, Rangari, Kumar, Reddy, Channale, Elango, Mir, Zwart, Laxuman, Sudini, Pandey, Punnuri, Mendu, Reddy, Guo, Gangarao, Sharma, Wang, Zhao and Thudi.)

Local anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (C max ) of bupivacaine was 152.03 (SD 37.34) ng/mL and its T max was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h -1 . No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Venkatachalam, Kells, Chambers, Jacob, Ward and Singh.)

Purpose: There is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline., Methods and Materials: Data was taken from a randomized control trial of 133 adults (age 18-70 years; ECOG performance score 0-2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.gov Identifier: NCT02206230). The delivered plan's dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data., Results: Toxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063-0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage., Conclusions: In this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The new 2,3-diphenylquinoxalin-6-amine (dpqa) was designed and synthesized through an efficient and high yield condensation process. Data from FTIR and 1 H-NMR spectroscopy have been adopted to ascertain the molecular structure of benzoxazine compounds. Furthermore, the quinoxaline amine based benzoxazine (BA-dpqa) was synthesized using bisphenol-A and paraformaldehyde followed by combining different weight percentages (1, 5 and 10 wt%) of (3-glycidyloxypropyl)trimethoxysilane functionalized CNT-PbS with benzoxazine to obtain nanocomposites. The thermal and morphological properties of the quinoxaline amine based neat polybenzoxazine matrix poly(BA-dpqa) and CNT-PbS/poly(BA-dpqa) composites were analysed by XRD, TGA and SEM analysis. The values of the degradation temperature ( T d ) obtained for neat poly(BA-dpqa) and 10 wt% CNT-PbS/poly(BA-dpqa) composites are 414 °C and 424 °C. Furthermore, the chair yield percentage was calculated as 33% and 35% respectively. The water contact angle of polybenzoxazine gradually increased from 89° to 127° proportional to the content of CNT-PbS. Among the composites, 10 wt% CNT-PbS reinforced poly(BA-dpqa) nanocomposites possess higher dielectric constant ( k = 11.0) than other composites. The pseudocapacitor nature of the prepared electrodes is demonstrated by the good electrochemical performance according to the CV curve. Also, the prepared 10 wt% CNT-PbS/poly(BA-dpqa) (637 F g -1 at 5 A g -1 and 11.8 Ω) electrode shows better capacitance and lower charge transfer resistance values than 5 wt% CNT-PbS/poly(BA-dpqa) (613 F g -1 at 5 A g -1 and 13.2 Ω) and neat poly(BA-dpqa) (105 F g -1 at 5 A g -1 and 15.6 Ω) according to the charge/discharge curves and EIS spectra. 10 wt% CNT-PbS/poly(BA-dpqa) shows 99.2% cycling efficiency even at the 2000th cycle, which indicates the good electrochemical performance of the prepared electrode.

Introduction: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD., Methods: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis., Results: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively., Conclusion: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia., Competing Interests: Declaration of Competing Interest All the authors assure that there are no commercial or financial involvements that might present an appearance of a conflict of interest in connection with this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bay of Bengal (BoB) has immense significance with respect to ecological diversity and natural resources. Studies on microbial profiling and their functional significance at sediment level of BoB remain poorly represented. Herein, we describe the microbial diversity and metabolic potentials of BOB deep-sea sediment samples by subjecting the metagenomes to Nanopore sequencing. Taxonomic diversity ascertained at various levels revealed that bacteria belonging to phylum Proteobacteria predominantly represented in sediment samples NIOT&#95;S7 and NIOT&#95;S9. A comparative study with 16S datasets from similar ecological sites revealed depth as a crucial factor in determining taxonomic diversity. KEGG annotation indicated that bacterial communities possess sequence reads corresponding to carbon dioxide fixation, sulfur, nitrogen metabolism, but at varying levels. Additionally, gene sequences related to bioremediation of dyes, plastics, hydrocarbon, antibiotic resistance, secondary metabolite synthesis and metal resistance from both the samples as studied indicate BoB to represent a highly diverse environmental niche for further exploration., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Chickpea ( Cicer arietinum L.) is one of the major pulse crops, rich in protein, and widely consumed all over the world. Most legumes, including chickpeas, possess noticeable amounts of raffinose family oligosaccharides (RFOs) in their seeds. RFOs are seed oligosaccharides abundant in nature, which are non-digestible by humans and animals and cause flatulence and severe abdominal discomforts. So, this study aims to identify genetic factors associated with seed oligosaccharides in chickpea using the mini-core panel. We have quantified the RFOs (raffinose and stachyose), ciceritol, and sucrose contents in chickpea using high-performance liquid chromatography. A wide range of variations for the seed oligosaccharides was observed between the accessions: 0.16 to 15.13 mg g -1 raffinose, 2.77 to 59.43 mg g -1 stachyose, 4.36 to 90.65 mg g -1 ciceritol, and 3.57 to 54.12 mg g -1 for sucrose. Kabuli types showed desirable sugar profiles with high sucrose, whereas desi types had high concentrations RFOs. In total, 48 single nucleotide polymorphisms (SNPs) were identified for all the targeted sugar types, and nine genes ( Ca&#95;06204, Ca&#95;04353 , and Ca&#95;20828 : Phosphatidylinositol N-acetylglucosaminyltransferase ; Ca&#95;17399 and Ca&#95;22050 : Remorin proteins ; Ca&#95;11152 : Protein-serine/threonine phosphatase; Ca&#95;10185, Ca&#95;14209 , and Ca&#95;27229 : UDP-glucose dehydrogenase ) were identified as potential candidate genes for sugar metabolism and transport in chickpea. The accessions with low RFOs and high sucrose contents may be utilized in breeding specialty chickpeas. The identified candidate genes could be exploited in marker-assisted breeding, genomic selection, and genetic engineering to improve the sugar profiles in legumes and other crop species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elango, Wang, Thudi, Sebastiar, Ramadoss and Varshney.)

Background: DNA binding with one finger (Dof) proteins are plant-specific transcription factor (TF) that plays a significant role in various biological processes such as plant growth and development, hormone regulation, and resistance to abiotic stress. The Dof genes have been identified and reported in multiple plants, but so far, the whole genome identification and analysis of Dof transcription factors in blueberry ( Vaccinium corymbosum L.) have not been reported yet., Methods: Using the Vaccinium genome, we have identified 51 VcDof genes in blueberry. We have further analyzed their physicochemical properties, phylogenetic relationships, gene structure, collinear analysis, selective evolutionary pressure, cis-acting promoter elements, and tissue and abiotic stress expression patterns., Results: Fifty-one VcDof genes were divided into eight subfamilies, and the genes in each subfamily contained similar gene structure and motif ordering. A total of 24 pairs of colinear genes were screened; VcDof genes expanded mainly due to whole-genome duplication, which was subjected to strong purifying selection pressure during the evolution. The promoter of VcDof genes contains three types of cis-acting elements for plant growth and development, phytohormone and stress defense responsiveness. Expression profiles of VcDof genes in different tissues and fruit developmental stages of blueberry indicated that VcDof2 and VcDof45 might play a specific role in anthesis and fruit growth and development. Expression profiles of VcDof genes in different stress indicated that VcDof1 , VcDof11 , and VcDof15 were highly sensitive to abiotic stress. This study provides a theoretical basis for further clarifying the biological function of Dof genes in blueberry., Competing Interests: The authors declare there are no competing interests., (©2022 Li et al.)

Dengue is an arboviral infection endemic in tropical countries. Neurological sequelae to dengue infection are not uncommon, and psychiatric manifestations are increasingly reported. This narrative review aims to present the varied manifestations, postulated mechanisms, and the available treatment options for psychiatric morbidity associated with dengue. The evidence available from eight observational studies is summarized in this review. Depression and anxiety are noted to be prevalent during both the acute and convalescent stages of the infection. The presence of encephalopathy and other neurological conditions is not a prerequisite for developing psychiatric disorders. However, treatment options to manage such psychiatric manifestations were not specified in the observational studies. Anecdotal evidence from case reports is outlined. Special attention is paid to the role of epigenetic modifications following dengue infections and the role of histone deacetylase inhibitors in the management. DNA methylation inhibitors such as valproic acid play a significant role in reversing stress-, viral-, or drug-induced epigenetic modifications., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 Indian Psychiatric Society - South Zonal Branch.)

A mesoporous silica hybrid functionalized with aromatic 1,2-phenyl dithiol (PT@MS NPs) was prepared in two steps such as sol-gel co-condensation of VTMS and tetraethyl orthosilicate (TEOS) using Pluronic P123 as a structure directing surfactant, and surface grafting reaction of 1,2-phenyl dithiol with vinyl groups via click-reaction. Surface area, average pore size, and mesopore volume of the produced PT@MS NPs are approximately 546 m 2 /g, 2.8 nm, and 0.63 cm 3 /g, respectively. With an adsorption quantity of 252 mg/g and a removal capacity of nearly 95% from the initial metal ion (100 mg/L of Hg 2+ ions) solutions, the PT@MS NPs material showed highly selective adsorption of mercury (Hg2+) from a mixture of other competitive metal (Zn 2+ , Ni 2+ , Pb 2+ , Cd 2+ , and Fe 2+ ) ions. By treating the adsorbent with an acidic aqueous solution (0.1 M HCl), the produced adsorbent can be recycled and reused up to five times. As a result, the PT@MS NPs adsorbent might be used in wastewater treatment as a highly efficient and selective adsorbent for harmful Hg 2+ ions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this research, an electrochemical sensor was fabricated employing the metal-organic framework (MOF) deposited glassy carbon electrode (GCE) for the sensing copper ions in water with high sensitivity. The porous nanostructured MOF was characterized through Transmission electron microscope, scanning electron microscope and X-ray diffraction analysis. The Bi-MOF nanostructure deposited GCE (Bi-MOF/GCE) was fabricated by drop-casting a suspension of Bi-MOF in water on GCE surface. The performance of modified electrode in the presence and absence of heavy metal ions such as Cd 2+ , Hg 2+ As 3+ , Pb 2+ and Cu 2+ was determined by the cyclic voltammetry in deionised water within the scan rate range of 25 and 300 mVs -1 . The Bi-MOF/GCE displayed highest anodic and cathodic peak current for Cu 2+ ions than other metal ions, which was enhanced linearly within the scan rate range of 10-100 mV s -1 . Under the employed experimental conditions, the fabricated Bi-MOF/GCE based electrochemical sensor showed an outstanding routine in the determination of copper with a lowest sensing limit of 1 × 10 -5  M, wide linear range variation, strong interaction between metal ions and Bi-MOF. It has long-term stability and good reproducibility. The Bi-MOF/GCE electrode was successfully tested to detect Cu 2+ in tap water with acceptable results., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bacterial infections in marine fishes are linked to mass mortality issues; hence, rapid detection of an infection can contribute to achieving a faster diagnosis using point-of-care testing. There has been substantial interest in identifying diagnostic biomarkers that can be detected in major organs to predict bacterial infections. Aspartate was identified as an important biomarker for bacterial infection diagnosis in olive flounder ( Paralichthys olivaceus ) fish. To determine aspartate levels, an amperometric biosensor was designed based on bi-enzymes, namely, glutamate oxidase (GluOx) and aspartate transaminase (AST), which were physisorbed on copolymer reduced graphene oxide (P-rGO), referred to as enzyme nanosheets (GluOx-ASTENs). The GluOx-ASTENs were drop casted onto a Prussian blue electrodeposited screen-printed carbon electrode (PB/SPCE). The proposed biosensor was optimized by operating variables including the enzyme loading amount, coreactant (α-ketoglutarate) concentration, and pH. Under optimal conditions, the biosensor displayed the maximum current responses within 10 s at the low applied potential of -0.10 V vs. the internal Ag/AgCl reference. The biosensor exhibited a linear response from 1.0 to 2.0 mM of aspartate concentrations with a sensitivity of 0.8 µA mM -1 cm -2 and a lower detection limit of approximately 500 µM. Moreover, the biosensor possessed high reproducibility, good selectivity, and efficient storage stability., Competing Interests: The authors declare no conflict of interest.

Photoacoustic remote sensing (PARS) microscopy is an emerging label-free optical absorption imaging modality. PARS operates by capturing nanosecond-scale optical fluctuations produced by photoacoustic pressures. These time-domain (TD) variations are usually projected by amplitude to determine optical absorption magnitude. However, valuable details on a target's material properties (e.g., density, speed of sound) are contained within the TD signals. This work uses a novel, to the best of our knowledge, clustering method to learn TD features, based on signal shape, which relate to underlying material traits. A modified K-means method is used to cluster TD data, capturing representative signal features. These features are then used to form virtual colorizations which may highlight tissues based on their underlying material properties. Applied in fresh resected murine brain tissue, colorized visualizations highlight distinct regions of tissue. This may potentially facilitate differentiation of tissue constituents (e.g., myelinated and unmyelinated axons, cell nuclei) in a single acquisition.

A voltammetric sensor for norepinephrine (NE) detection was developed by modifying a disposable screen-printed carbon electrode (SPCE) with de-bundled single-walled carbon nanotubes (D-SWCNTs). The de-bundling was carried out using a newly synthesized polymeric dispersant, a co-polymer of polystyrene sulfonate and methacrylate of lipoic acid. The D-SWCNTs/SPCE showed better sensitivity towards NE compared to the bare SPCE and that modified with bundled SWCNTs. The sensor was optimized for detecting NE by differential pulse voltammetry (DPV) in terms of the D-SWCNTs concentration, DPV parameters, and solution pH. Under the optimum conditions, the sensor exhibited a dynamic linear range of 100 nM-2.0 µM NE, and the detection limit was 62.0 nM (S/N = 3). Additionally, the effects of possible interferents were investigated. The relative standard deviation for five successive measurements of 2.0 µM NE was 7.6%, and approximately 75.8% of the sensor activity was retained after four weeks of storage. The practical potential of this sensor was demonstrated by quantifying NE in ex vivo rat tissue samples., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Liver disease is the only major chronic disease and mortality is increasing. Earlier detection of liver fibrosis can reduce progression to cirrhosis and hepatocellular carcinoma. Many studies have reported an increased prevalence in liver fibrosis among adults in urban regions but there are few data in physically active rural populations without attributable metabolic risk factors. This aim of this study is to investigate the prevalence of abnormal liver functions tests (LFTs) and liver fibrosis among adults in a rural population., Methods: This cross-sectional study included observations from KMCH-NNCD-II (2017) study ( n  = 907) from a farming village, Nallampatti, located in South India. We assessed lifestyle (occupation, tobacco use and alcohol consumption using AUDIT-C questionnaire), markers for metabolic diseases (obesity, hypertension, diabetes, hypercholesterolemia), LFTs and markers for hepatitis viruses B and C. 901 participants had transient elastography to assess fibrosis. Participants with abnormal LFTs and significant liver fibrosis (F2-F4) underwent additional liver screening (caeruloplasmin, iron studies and autoimmune hepatitis panel). Multiple logistic regression analyses were performed to understand the association of liver fibrosis with lifestyle and metabolic risk factors after adjustment for co-variates., Findings: Significant liver fibrosis (F2-F4) was observed in 14.4%, and cirrhosis in 0.8%. There was an association of liver fibrosis with abnormal LFTs but no association between alcohol consumption, viral hepatitis, hepatic liver screening and liver fibrosis. Among metabolic risk factors, no association was observed for hypertension and hypercholesterolemia but diabetes [OR - 3.206 (95% CI: 1.792 - 5.736)], obesity [1.987 (1.341 - 2.944)] and metabolic syndrome [2.539 (1.680 - 3.836)] showed association with significant liver fibrosis (F2-F4) after adjustment for confounding factors., Interpretation: Our results suggest that the prevalence of liver fibrosis in rural population is similar to urban counterparts. The association of metabolic risk factors with liver fibrosis in physically active rural population warrants further investigations in future studies., Funding: This study is funded by KMCH Research Foundation, India., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

Auditory Signal Detection (ASD) theory postulates that auditory verbal hallucinations (AVH) result from an aberrant association of meaningful connection to abstract noises. In this study, schizophrenia (SZ) patients with persistent AVH (N = 17) and matched controls (N = 25) performed an ASD task with concurrent functional near-infrared spectroscopy recording targetting the left dorsolateral prefrontal cortex (L-DLPFC) and left temporoparietal junction (L-TPJ). During the task, discriminability index had a significant negative correlation, and early deoxyhemoglobin (HbR) latency at L-TPJ positively correlated with AVH scores. Also, patients had significantly lower discriminability, early HbR latency at L-TPJ, and delayed latency at L-DLPFC. This finding suggests the presence of ASD abnormalities and impaired auditory processing in SZ patients with AVH supporting ASD-based pathogenesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Histopathological visualizations are a pillar of modern medicine and biological research. Surgical oncology relies exclusively on post-operative histology to determine definitive surgical success and guide adjuvant treatments. The current histology workflow is based on bright-field microscopic assessment of histochemical stained tissues and has some major limitations. For example, the preparation of stained specimens for brightfield assessment requires lengthy sample processing, delaying interventions for days or even weeks. Therefore, there is a pressing need for improved histopathology methods. In this paper, we present a deep-learning-based approach for virtual label-free histochemical staining of total-absorption photoacoustic remote sensing (TA-PARS) images of unstained tissue. TA-PARS provides an array of directly measured label-free contrasts such as scattering and total absorption (radiative and non-radiative), ideal for developing H&E colorizations without the need to infer arbitrary tissue structures. We use a Pix2Pix generative adversarial network to develop visualizations analogous to H&E staining from label-free TA-PARS images. Thin sections of human skin tissue were first virtually stained with the TA-PARS, then were chemically stained with H&E producing a one-to-one comparison between the virtual and chemical staining. The one-to-one matched virtually- and chemically- stained images exhibit high concordance validating the digital colorization of the TA-PARS images against the gold standard H&E. TA-PARS images were reviewed by four dermatologic pathologists who confirmed they are of diagnostic quality, and that resolution, contrast, and color permitted interpretation as if they were H&E. The presented approach paves the way for the development of TA-PARS slide-free histological imaging, which promises to dramatically reduce the time from specimen resection to histological imaging., (© 2022. The Author(s).)

In the past decades, absorption modalities have emerged as powerful tools for label-free functional and structural imaging of cells and tissues. Many biomolecules present unique absorption spectra providing chromophore-specific information on properties such as chemical bonding, and sample composition. As chromophores absorb photons the absorbed energy is emitted as photons (radiative relaxation) or converted to heat and under specific conditions pressure (non-radiative relaxation). Modalities like fluorescence microscopy may capture radiative relaxation to provide contrast, while modalities like photoacoustic microscopy may leverage non-radiative heat and pressures. Here we show an all-optical non-contact total-absorption photoacoustic remote sensing (TA-PARS) microscope, which can capture both radiative and non-radiative absorption effects in a single acquisition. The TA-PARS yields an absorption metric proposed as the quantum efficiency ratio (QER), which visualizes a biomolecule's proportional radiative and non-radiative absorption response. The TA-PARS provides label-free visualization of a range of biomolecules enabling convincing analogues to traditional histochemical staining of tissues, effectively providing label-free Hematoxylin and Eosin (H&E)-like visualizations. These findings establish an effective all-optical non-contact total-absorption microscope for label-free inspection of biological materials., (© 2022. The Author(s).)

A psychiatrist, in India, unlike in the western developed world often is required to play dual role of being a treating psychiatrist and that of an expert witness for the same patient. In the clinical scenario, the principle of therapeutic alliance comes into play, while in the court of law, he/she needs to play the role of assisting the judicial system to deliver "justice." Psychiatrist role in the court is directed by the court rules and not by the clinical rules. This chapter aims to describe the various roles played by the psychiatrist in the court room and provides a basic outline of the medicolegal expectations from a psychiatrist., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Psychiatry.)

Nutraceutical agents and food supplements are commonly used as treatment adjuncts in neuropsychiatric disorders. Curcumin, a bioactive agent obtained from the rhizome of Curcuma longa , with its antioxidant and anti-inflammatory properties, has gained much research attention in the last few decades. In this narrative review, we intend to summarize the evidence available for curcumin as an add-on agent in the management of schizophrenia. We searched PubMed/EBSCO for both human and animal trials utilizing curcumin in the management of schizophrenia. We obtained ten articles (five preclinical and five clinical) from the focused literature search. Clinical research utilizing curcumin in schizophrenia is limited to negative and cognitive symptoms. Available preclinical studies suggest curcumin's utility in ameliorating extrapyramidal and metabolic side effects when given as an adjunct with antipsychotics. Curcumin, as an add-on agent, appears promising to improve the negative and cognitive symptoms of schizophrenia. Notably, curcumin was tolerable and safe in all the randomized human clinical trials. The poor oral bioavailability is, however, a limiting factor in its widespread use., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 Indian Psychiatric Society - South Zonal Branch.)

Raffinose family oligosaccharides (RFOs) are widespread across the plant kingdom, and their concentrations are related to the environment, genotype, and harvest time. RFOs are known to carry out many functions in plants and humans. In this paper, we provide a comprehensive review of RFOs, including their beneficial and anti-nutritional properties. RFOs are considered anti-nutritional factors since they cause flatulence in humans and animals. Flatulence is the single most important factor that deters consumption and utilization of legumes in human and animal diets. In plants, RFOs have been reported to impart tolerance to heat, drought, cold, salinity, and disease resistance besides regulating seed germination, vigor, and longevity. In humans, RFOs have beneficial effects in the large intestine and have shown prebiotic potential by promoting the growth of beneficial bacteria reducing pathogens and putrefactive bacteria present in the colon. In addition to their prebiotic potential, RFOs have many other biological functions in humans and animals, such as anti-allergic, anti-obesity, anti-diabetic, prevention of non-alcoholic fatty liver disease, and cryoprotection. The wide-ranging applications of RFOs make them useful in food, feed, cosmetics, health, pharmaceuticals, and plant stress tolerance; therefore, we review the composition and diversity of RFOs, describe the metabolism and genetics of RFOs, evaluate their role in plant and human health, with a primary focus in grain legumes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elango, Rajendran, Van der Laan, Sebastiar, Raigne, Thaiparambil, El Haddad, Raja, Wang, Ferela, Chiteri, Thudi, Varshney, Chopra, Singh and Singh.)

Parkinson's disease (PD) is a progressive movement disorder caused by nigrostriatal neurodegeneration. Since chronically activated neuroinflammation accelerates neurodegeneration in PD, we considered that modulating chronic neuroinflammatory response might provide a novel therapeutic approach. Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine protein kinase with two isoforms, GSK-3α and GSK-3β, and GSK-3β plays crucial roles in inflammatory response, which include microglial migration and peripheral immune cell activation. GSK-3β inhibitory peptide (IAGIP) is specifically activated by activated inhibitory kappa B kinase (IKK), and its therapeutic effects have been demonstrated in a mouse model of colitis. Here, we investigated whether the anti-inflammatory effects of IAGIP prevent neurodegeneration in the rodent model of PD. IAGIP significantly reduced MPP + -induced astrocyte activation and inflammatory response in primary astrocytes without affecting the phosphorylations of ERK or JNK. In addition, IAGIP inhibited LPS-induced cell migration and p65 activation in BV-2 microglial cells. In vivo study using an MPTP-induced mouse model of PD revealed that intravenous IAGIP effectively prevented motor dysfunction and nigrostriatal neurodegeneration. Our findings suggest that IAGIP has a curative potential in PD models and could offer new therapeutic possibilities for targeting PD.

With increasing drug resistance in tuberculosis (TB) patient populations, there is an urgent need for new drugs. Ideally, new agents should work through novel targets so that they are unencumbered by preexisting clinical resistance to current treatments. Benzofuran 1 was identified as a potential lead for TB inhibiting a novel target, the thioesterase domain of Pks13. Although, having promising activity against Mycobacterium tuberculosis , its main liability was inhibition of the hERG cardiac ion channel. This article describes the optimization of the series toward a preclinical candidate. Despite improvements in the hERG liability in vitro, when new compounds were assessed in ex vivo cardiotoxicity models, they still induced cardiac irregularities. Further series development was stopped because of concerns around an insufficient safety window. However, the demonstration of in vivo activity for multiple series members further validates Pks13 as an attractive novel target for antitubercular drugs and supports development of alternative chemotypes.

Background Integrating psychiatric care into the general practice of primary care doctors (PCDs) is necessary to overcome the shortage of human resources to cater to the burgeoning public mental health needs of India. The traditional psychiatry curriculum is often top-down and specialist-based that contributes little in terms of skill quotient. We designed an innovative, digitally driven, distance education-based, part-time, modular-based Primary Care Psychiatry Programme (PCPP, skill-based). It is being implemented across many states of India to equip PCDs with skills to provide first-line psychiatry treatment. We discuss the rationale and guiding principles behind designing the curriculum of PCPP. Discussion There are nine guiding principles behind designing and implementing PCPP to provide pragmatic, acceptable, feasible modules of higher translational quotient (TQ) that are essential to upskill PCDs. There is a shift in training the location of PCDs in their live brief general consultations utilizing innovative telemedicine-based 'on-consultation training' (OCT) augmented with collaborative video consultations. A monolithic treatment protocol-driven, trans-diagnostic approach is used to design a concise, all-inone, point-of-care manual containing a culturally sensitive, rapid, validated screener and taxonomy, called 'Clinical Schedules for Primary Care Psychiatry'. This incorporates the PCDs' style of clinical practice that helps in picking up the most commonly prevalent adult psychiatric disorders presenting to primary care. Conclusion This PCPP curriculum contains pragmatic modules with higher TQ. This curriculum is dynamic as the learning is bi-directional. This can be used by policy-makers, innovators and academia for integration with national health programmes such as those for non-communicable diseases and reproductive and child health.

Green thermoplastic starch (TPS) nanocomposite films aided by cellulose nanofibers (CNFs) from Chrysopogon zizanioides roots were developed and characterized. When compared to other lignocellulosic fibers, Chrysopogon zizanioides roots revealed exceptionally high cellulose content (~48%). CNFs were separated using an environmentally friendly acid isolation technique that included three stages: (i) alkali treatment; (ii) bleaching; and (iii) mild acid hydrolysis using oxalic acid in an autoclave. Following that, green nanocomposite films were made from potato starch using the solution casting process, by which we used glycerol (30 wt%) to make thermoplastic starch. Then, cellulose nanofibers in different concentrations (0, 1, 2, 3, 4 wt%) were added to the thermoplastic starch matrix. The isolated CNFs had diameters in the range of 17-27 nm. Besides, these nanostructures presented a very high crystallinity index (~65%), thereby enhanced the thermal stability. TPS/CNF green nanocomposites containing 3 wt% CNFs had exceptional tensile strength (~161%), tensile modulus (~167%), thermal stability, and crystallinity. As a result, nanocomposite films made of starch and cellulose nanofibers (3 wt%) extracted from Chrysopogon zizanioides roots would be alternatives for sustainable packaging. It can be concluded that Chrysopogon zizanioides roots have high potential for polymer industry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.

Bacterial infections in fish farms increase mass mortality and rapid detection of infection can help prevent its widespread. Lactate is an important biomarker for early diagnosis of bacterial infections in farmed olive flounder ( Paralichthys olivaceus ). To determine the lactate levels, we designed a disposable amperometric biosensor based on Prussian blue nanozyme and lactate oxidase (LOX) entrapped in copolymer-reduced graphene oxide (P-rGO) on screen-printed carbon electrodes. Because LOX is inherently unstable, P-rGO nanosheets were utilized as a base matrix to immobilize it. After optimization in terms of enzyme loading, operating potential, and pH, the biosensor displayed maximum current responses within 5 s at the applied potential of -0.1 V vs. internal Ag/AgCl. The biosensor had Langmuir-type response in the lactate concentration range from 10 µM to 1.6 mM, a dynamic linear response range of 10-100 µM, a sensitivity of 15.9 µA mM -1 cm -2 , and a lower detection limit of 3.1 µM (S/N = 3). Additionally, the biosensor featured high reproducibility, good selectivity, and stability till four weeks. Its practical applicability was tested in olive flounder infected by Streptococcus parauberis against the uninfected control. The results were satisfactory compared to those of a standard colorimetric assay kit, validating our method.

Background: Obsessive-compulsive disorder (OCD) is increasingly being evaluated for a neuro-immune basis. Interleukin-6 (IL-6) is the most widely studied cytokine with a potential role in altering neurotransmission. The evidence for plasma IL-6 alterations in OCD has yielded mixed results. Psychotropic medications are known to modulate inflammatory processes and cytokine levels., Methods: In this study, we recruited unmedicated, co-morbidity-free adult OCD patients ( n  = 49) and sex-matched healthy controls HC ( n  = 47) and compared their plasma IL-6 levels and their correlation with age at onset, duration of illness, and severity., Results: IL-6 plasma level (ng/ml) in unmedicated OCD patients (1.31 ± 0.67) was significantly greater compared to HC (1.03 ± 0.47) [ t  = 2.33 ( p  = 0.02)]. The group differences persisted even after controlling for age and sex [ F (1, 91) = 4.57, p  = 0.035, η 2 = 0.05]. Plasma IL-6 did not correlate significantly with any clinical variables., Conclusions: This study adds to the existing literature on immune alterations in OCD. Alterations in plasma IL-6 might have implications in the neurotransmitter alterations and stress-response in OCD. The current study results in unmedicated and comorbidity-free OCD patients give us a better understanding of the immune alterations in OCD. Future studies in such a population will probably help in reducing the heterogeneity of findings.

Dopamine (DA) and ascorbic acid (AA) are two important biomarkers with similar oxidation potentials. To facilitate their simultaneous electrochemical detection, a new voltammetric sensor was developed by modifying a screen-printed carbon electrode (SPCE) with a newly synthesized block copolymer (poly(DMAEMA- b -styrene), PD b S) as a dispersant for reduced graphene oxide (rGO). The prepared PD b S-rGO and the modified SPCE were characterized using a range of physical and electrochemical techniques including Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and linear sweep voltammetry. Compared to the bare SPCE, the PD b S-rGO-modified SPCE (PD b S-rGO/SPCE) showed better sensitivity and peak-to-peak separation for DA and AA in mixed solutions. Under the optimum conditions, the dynamic linear ranges for DA and AA were 0.1-300 and 10-1100 µM, and the detection limits were 0.134 and 0.88 µM (S/N = 3), respectively. Furthermore, PD b S-rGO/SPCE exhibited considerably enhanced anti-interference capability, high reproducibility, and storage stability for four weeks. The practical potential of the PD b S-rGO/SPCE sensor for measuring DA and AA was demonstrated using ex vivo brain tissues from a Parkinson's disease mouse model and the control.

A new disposable amperometric biosensor for sarcosine (Sar, a biomarker for prostate cancer) was designed based on screen-printed carbon electrodes, Prussian blue, polymer dispersed reduced graphene oxide (P-rGO) nanosheets, and sarcosine oxidase (SOx). Poly(sodium 4-styrenesulfonate-r-LAHEMA) denoted as PSSL was newly synthesized as dispersant for rGO. The P-rGO was utilized for SOx immobilization, the sulfonate and disulfide functionalities in PSSL enable physical adsorption of SOx and its bioactivity and stability properties were improved. The biosensor was optimized by various enzyme concentration, applied potential, and operating pH. Under the optimized conditions, the biosensor exhibited maximum current responses within 5 s at an applied potential of -0.1 V vs. integrated Ag/AgCl reference electrode. The biosensor had a dynamic linear range of 10-400 μM, with a sensitivity of 9.04 μA mM -1  cm -2 and a low detection limit of 0.66 μM (S/N = 3). Additionally, the biosensor possesses strong anti-interference capability, high reproducibility, and storage stability over 3 weeks. Furthermore, its clinical applicability was tested in urine samples from both prostate cancer patients and healthy control, and the analytical recoveries were satisfactory. Therefore, this biosensor has significant potential in the rapid and non-invasive point-of-care testing for prostate cancer diagnosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seung-Cheol Chang reports financial support was provided by National Research Foundation of Korea. Suhkmann Kim reports financial support was provided by Korea Ministry of Oceans and Fisheries. Hyun-jong Paik reports financial support was provided by National Research Foundation of Korea., (Copyright © 2021 Elsevier B.V. All rights reserved.)

COVID-19, an infectious disease caused by a novel coronavirus (SARS-CoV-2) has emerged as global pandemic. Here, we described the changes in microbiota of upper respiratory tract by analyzing the publically available RNA sequencing data of SARS-CoV-2-infected ferrets. The bacterial dysbiosis due to SARS-CoV-2 was largely inversely proportional to the dysbiosis caused by influenza-A virus. The bacterial taxa which are defined as healthy ecostate were significantly reduced during SARS-CoV-2 infection. Altogether, this preliminary study provides a new insight on the possible role of bacterial communities of upper respiratory tract in determining the immunity, susceptibility, and mortality for COVID-19., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Histological images are critical in the diagnosis and treatment of cancers. Unfortunately, current methods for capturing these microscopy images require resource intensive tissue preparation that may delay diagnosis for days or weeks. To streamline this process, clinicians are limited to assessing small macroscopically representative subsets of tissues. Here, a combined photoacoustic remote sensing (PARS) microscope and swept source optical coherence tomography system designed to circumvent these diagnostic limitations is presented. The proposed multimodal microscope provides label-free three-dimensional depth resolved virtual histology visualizations, capturing nuclear and extranuclear tissue morphology directly on thick unprocessed specimens. The capabilities of the proposed method are demonstrated directly in unprocessed formalin fixed resected tissues. The first images of nuclear contrast in resected human tissues, and the first three-dimensional visualization of subsurface nuclear morphology in resected Rattus tissues, captured with a non-contact photoacoustic system are presented here. Moreover, the proposed system captures the first co-registered OCT and PARS images enabling direct histological assessment of unprocessed tissues. This work represents a vital step towards the development of a rapid histological imaging modality to circumvent the limitations of current histopathology techniques.

Competing Interests: There are no conflicts of interest.

Coenzyme A (CoA) is a ubiquitous cofactor present in all living cells and estimated to be required for up to 9% of intracellular enzymatic reactions. Mycobacterium tuberculosis (Mtb) relies on its own ability to biosynthesize CoA to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the pathway to CoA biosynthesis is recognized as a potential source of novel tuberculosis drug targets. In prior work, we genetically validated CoaBC as a bactericidal drug target in Mtb in vitro and in vivo . Here, we describe the identification of compound 1f , a small molecule inhibitor of the 4'-phosphopantothenoyl-l-cysteine synthetase (PPCS; CoaB) domain of the bifunctional Mtb CoaBC, and show that this compound displays on-target activity in Mtb. Compound 1f was found to inhibit CoaBC uncompetitively with respect to 4'-phosphopantothenate, the substrate for the CoaB-catalyzed reaction. Furthermore, metabolomic profiling of wild-type Mtb H37Rv following exposure to compound 1f produced a signature consistent with perturbations in pantothenate and CoA biosynthesis. As the first report of a direct small molecule inhibitor of Mtb CoaBC displaying target-selective whole-cell activity, this study confirms the druggability of CoaBC and chemically validates this target.

The errata correct the errors in citation numbering that appeared in the originally published article.

Introduction: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients., Methods: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS., Results: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients., Conclusion: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future., (Copyright © 2021. Published by Elsevier B.V.)

Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids., Study Design: Experimental prospective study., Animals: A total of 18 (n = 6 animals per experiment) male Saanen goat kids (2-4 weeks old)., Methods: The study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg -1 ). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg -1 minute -1 ). Data are shown as mean ± standard deviation., Results: The mean terminal half-life (t 1/2λz ), mean volume of distribution at steady state (Vd ss ) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg -1 and 5.33 L hour -1 kg -1 , respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL -1 at 0.22 hour and its mean t 1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg -1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL -1 , respectively., Conclusions: Intravenous administration of 8 mg kg -1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding., Clinical Relevance: Articaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Gastrointestinal (GI) tissue biopsies provide critical diagnostic information for a wide variety of conditions such as neoplastic diseases (colorectal, small bowel and stomach cancers) and non-neoplastic diseases (inflammatory disorders, infection, celiac disease). Endoscopic biopsies collect small tissue samples that require resource intensive processing to permit histopathological analysis. Unfortunately, the sparsely collected biopsy samples may fail to capture the pathologic condition because selection of biopsy sites relies on macroscopic superficial tissue features and clinician judgement. Here, we present the first all-optical non-contact label-free non-interferometric photoacoustic microscopy system capable of performing "virtual biopsies". A modular photoacoustic remote sensing (PARS™) architecture is used facilitating imaging of unprocessed tissues providing information similar to conventional histopathological staining techniques. Prospectively this would allow gastroenterologists to assess subcellular tissue morphology in situ when selecting biopsy location. Tested on preserved unstained human and freshly resected murine tissues, the presented PARS microscope rapidly retrieves images of similar area to current biopsies, while maintaining comparable quality to the current standard for histopathological analysis. Additionally, results show the first label free assessment of subsurface cellular morphology in FFPE GI tissue blocks. Clinically relevant features are recovered including cellular details such as lamina propria within colon tissue and cell nuclear structure in resected smooth muscle. Constructed with a modular architecture, this system facilitates the future development of compact imaging heads. The modular PARS system overcomes many of the challenges with imaging unstained thick tissue in situ , representing a significant milestone in the development of a clinical microscope providing virtual biopsy capabilities., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-722). The special issue “Advanced Optical Imaging in Biomedicine” was commissioned by the editorial office without any funding or sponsorship. KB, DD, JRM and PHR have financial interests in illumiSonics Inc. IllumiSonics partially supported this work. The authors have no other conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

A new type of disposable flexible sensor for hydrogen peroxide (H2O2) detection was developed by in situ synthesis of copper-ruthenium bimetallic nanoparticles on a laser-induced graphene surface (Cu-Ru/LIG). The approach produced Cu-Ru/LIG via a solid phase transfer mechanism which loaded the metal precursor onto LIG, followed by laser scribing without demanding chemical vapor deposition or solution-based reactions. Cu-Ru/LIG showed a high electrocatalytic response toward H2O2 reduction at -0.4 V vs. Ag/AgCl. The sensor also showed good selectivity and reproducibility. This method provides an alternative route to easily synthesize various catalysts on conductive substrates for sensor applications.

We propose a new process for peer review of multidisciplinary journal submissions called 'segmented peer review'. The current translational research environment increasingly requires complex and multidisciplinary studies that span multiple distinct specialties within a single paper. Such papers present logistic and practical barriers to effective peer review. To address these barriers, papers undergoing segmented peer review require authors to explicitly i) identify each of the areas of expertise required to review the paper, ii) direct each reviewer to the relevant portions of the manuscript, and iii) suggest in-field reviewers. This segmentation of the paper is then followed by a 'segmented peer review request' tailored to the expertise of each potential reviewer, with a request to confine his / her review to those 'in-scope' aspects of the paper, while de-emphasizing any optional 'out-of-scope' comments. Each reviewer indicates the fitness for publication, or suitability for revision, of their particular segment of the manuscript. The segmented peer review process is completed when the editors integrate the segmented peer reviews. We propose segmented peer review as a fit-for-purpose process with tangible advantages for authors, reviewers, and journal editors. It should reduce the specific barriers to publication inherent in the evaluation of multidisciplinary research efforts., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Available evidence highlights that persons diagnosed with schizophrenia are predisposed to develop physical co-morbidities. Lifestyle modification interventions are identified as appropriate strategies to maintain their physical health. A comprehensive understanding of the facilitators and barriers in adhering to healthy lifestyle interventions is critical to developing individualized interventions that are effective and accessible for these patients., Aim: To develop and formulate a theory of lifestyle adaptation for the prevention of physical co-morbidities for persons with schizophrenia and their caregivers who are availing mental health services in the psychiatry wards., Materials and Methods: The qualitative data were collected by semi-structured interviews using topic guides from persons with schizophrenia and their family caregivers from the tertiary level psychiatry center, South India. The interviews explored their perceptions and experiences of the facilitators and barriers in adopting a healthy lifestyle. Final data was analyzed based on grounded theory, and the data was used to formulate the theory of lifestyle adaptation., Conclusion: The persons with schizophrenia and their family caregivers' perceptions helped in formulating this theory. The present study provides recommendations for physical health services for patients with mental illness. The findings of the study may guide health professionals and mental health advocacy groups, policymakers to plan for appropriate decisions related to incorporating mental health care with physical health care services., (Copyright © 2020 Elsevier B.V. All rights reserved.)

With the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis, there is a pressing need for new oral drugs with novel mechanisms of action. A number of scaffolds with potent anti-tubercular in vitro activity have been identified from phenotypic screening that appear to target MmpL3. However, the scaffolds are typically lipophilic, which facilitates partitioning into hydrophobic membranes, and several contain basic amine groups. Highly lipophilic basic amines are typically cytotoxic against mammalian cell lines and have associated off-target risks, such as inhibition of human ether-à-go-go related gene (hERG) and IKr potassium current modulation. The spirocycle compound 3 was reported to target MmpL3 and displayed promising efficacy in a murine model of acute tuberculosis (TB) infection. However, this highly lipophilic monobasic amine was cytotoxic and inhibited the hERG ion channel. Herein, the related spirocycles ( 1-2 ) are described, which were identified following phenotypic screening of the Eli Lilly corporate library against M. tuberculosis . The novel N-alkylated pyrazole portion offered improved physicochemical properties, and optimization led to identification of a zwitterion series, exemplified by lead 29 , with decreased HepG2 cytotoxicity as well as limited hERG ion channel inhibition. Strains with mutations in MmpL3 were resistant to 29 , and under replicating conditions, 29 demonstrated bactericidal activity against M. tuberculosis . Unfortunately, compound 29 had no efficacy in an acute model of TB infection; this was most likely due to the in vivo exposure remaining above the minimal inhibitory concentration for only a limited time., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Telemedicine Guidelines of India, 2020 promises to pave a road map for regularization and diversification of teleconsultation services across the country. This guideline is the need of the hour, especially during the current coronavirus disease pandemic. All modes of communications (text, audio, video, etc.) between the service provider and user are included in the broad rubric of the guidelines. Scope, inclusions, exclusions, and restrictions are clearly specified in the guideline. Medications are grouped and listed for the specific type of consultation, and restricted drugs are notified. This guideline especially helps mitigate the gaps in legislation and reduces the uncertainty while providing a practical, safe, and cost-effective framework to improve healthcare service delivery in this article; the authors discuss the implications of this new guideline and the challenges during the implementation of teleconsultation services across the country., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Psychiatry.)