Neuronal Population Encoding of Identity in Primate Prefrontal Cortex.

The ventrolateral prefrontal cortex (VLPFC) shows robust activation during the perception of faces and voices. However, little is known about what categorical features of social stimuli drive neural activity in this region. Since perception of identity and expression are critical social functions, we examined whether neural responses to naturalistic stimuli were driven by these two categorical features in the prefrontal cortex. We recorded single neurons in the VLPFC, while two male rhesus macaques (Macaca mulatta) viewed short audiovisual videos of unfamiliar conspecifics making expressions of aggressive, affiliative, and neutral valence. Of the 285 neurons responsive to the audiovisual stimuli, 111 neurons had a main effect (two-way ANOVA) of identity, expression, or their interaction in their stimulus-related firing rates; however, decoding of expression and identity using single-unit firing rates rendered poor accuracy. Interestingly, when decoding from pseudo-populations of recorded neurons, the accuracy for both expression and identity increased with population size, suggesting that the population transmitted information relevant to both variables. Principal components analysis of mean population activity across time revealed that population responses to the same identity followed similar trajectories in the response space, facilitating segregation from other identities. Our results suggest that identity is a critical feature of social stimuli that dictates the structure of population activity in the VLPFC, during the perception of vocalizations and their corresponding facial expressions. These findings enhance our understanding of the role of the VLPFC in social behavior.

Methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia.

Methotrexate, an immunomodulatory agent used for a wide variety of indications, can cause pulmonary toxicity in the form of pneumonitis, organising pneumonia, pulmonary fibrosis, pleural effusion, pulmonary infections or lymphoproliferative disease. We report a case of methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia. The diagnosis of methotrexate pneumonitis is challenging, as the signs and symptoms can be caused by intercurrent infection, concomitant medications or an underlying disease condition. A high index of suspicion is required for diagnosis. Management consists of drug discontinuation and steroids in patients with respiratory failure.

Graph deep network for optic disc and optic cup segmentation for glaucoma disease using retinal imaging.

The fundus imaging method of eye screening detects eye diseases by segmenting the optic disc (OD) and optic cup (OC). OD and OC are still challenging to segment accurately. This work proposes three-layer graph-based deep architecture with an enhanced fusion method for OD and OC segmentation. CNN encoder-decoder architecture, extended graph network, and approximation via fusion-based rule are explored for connecting local and global information. A graph-based model is developed for combining local and overall knowledge. By extending feature masking, regularization of repetitive features with fusion for combining channels has been done. The performance of the proposed network is evaluated through the analysis of different metric parameters such as dice similarity coefficient (DSC), intersection of union (IOU), accuracy, specificity, sensitivity. Experimental verification of this methodology has been done using the four benchmarks publicly available datasets DRISHTI-GS, RIM-ONE for OD, and OC segmentation. In addition, DRIONS-DB and HRF fundus imaging datasets were analyzed for optimizing the model's performance based on OD segmentation. DSC metric of methodology achieved 0.97 and 0.96 for DRISHTI-GS and RIM-ONE, respectively. Similarly, IOU measures for DRISHTI-GS and RIM-ONE datasets were 0.96 and 0.93, respectively, for OD measurement. For OC segmentation, DSC and IOU were measured as 0.93 and 0.90 respectively for DRISHTI-GS and 0.83 and 0.82 for RIM-ONE data. The proposed technique improved value of metrics with most of the existing methods in terms of DSC and IOU of the results metric of the experiments for OD and OC segmentation.

Precision Postbiotics and Mental Health: the Management of Post-COVID-19 Complications.

The health catastrophe originated by COVID-19 pandemic construed profound impact on a global scale. However, a plethora of research studies corroborated convincing evidence conferring severity of infection of SARS-CoV-2 with the aberrant gut microbiome that strongly speculated its importance for development of novel therapeutic modalities. The intense exploration of probiotics has been envisaged to promote the healthy growth of the host, and restore intestinal microecological balance through various metabolic and physiological processes. The demystifying effect of probiotics cannot be defied, but there exists a strong skepticism related to their safety and efficacy. Therefore, molecular signature of probiotics termed as "postbiotics" are of paramount importance and there is continuous surge of utilizing postbiotics for enhancing health benefits, but little is explicit about their antiviral effects. Therefore, it is worth considering their prospective role in post-COVID regime that pave the way for exploring the pastoral vistas of postbiotics. Based on previous research investigations, the present article advocates prospective role of postbiotics in alleviating the health burden of viral infections, especially SARS-CoV-2. The article also posits current challenges and proposes a futuristic model describing the concept of "precision postbiotics" for effective therapeutic and preventive interventions that can be used for management of this deadly disease.

Natural antioxidants for neuroinflammatory disorders and possible involvement of Nrf2 pathway: A review.

The transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) play a crucial role in cellular redox and metabolic system. Activation of Nrf2 may be an effective therapeutic approach for neuroinflammatory disorders, through activation of antioxidant defences system, lower the inflammation, line up the mitochondrial function, and balancing of protein homeostasis. Various recent studies revealed that many of active substance obtained from plants have been found to activate the Nrf2 and to exert neuroprotective effects in various experimental models, raising the possibility that activation of Nrf2 may be an effective therapeutic approaches for neuroinflammatory disorders. The objective of this review was to evaluate the neuroprotective property of natural substance against neuroinflammatory disorders by reviewing the studies done till today. The outcomes of various in vitro and in vivo examinations have shown that natural compounds producing neuroprotective effects in neuronal system via activation of Nrf2. Herein, we also reviewed the studies to understand the role of Nrf2 for curing CNS disorders. Here we can conclude, herbal/natural moieties having potency to fight and prevent from neuroinflammatory disorders due to their abilities to activate Nrf2 pathway.

Gut-organ axis: a microbial outreach and networking.

Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well-being and survival of the organism. It has been reported as diverse and relatively stable with shared core microbiota, including Bacteroidetes and Firmicutes as the major dominants. They are the key regulators of body homeostasis, involving both intestinal and extra-intestinal effects by influencing many physiological functions such as metabolism, maintenance of barrier homeostasis, inflammation and hematopoiesis. Any alteration in GM community structures not only trigger gut disorders but also influence other organs and cause associated diseases. In recent past, the GM has been defined as a 'vital organ' with its involvement with other organs; thus, establishing a link or a bi- or multidirectional communication axis between the organs via neural, endocrine, immune, humoral and metabolic pathways. Alterations in GM have been linked to several diseases known to humans; although the exact interaction mechanism between the gut and the organs is yet to be defined. In this review, the bidirectional relationship between the gut and the vital human organs was envisaged and discussed under several headings. Furthermore, several disease symptoms were also revisited to redefine the communication network between the gut microbes and the associated organs.

Hyperleptinaemia and its Association with Postprandial Hypertriglyceridemia and Glucose Intolerance.

Introduction: Leptin resistance is believed to cause insulin resistance though the exact mechanism is not fully understood. The present study aims to investigate the temporal profile of postprandial triglyceride (PPTG) and leptin levels, and their association with each other as well as with markers of metabolic syndrome. Materials and Methods: Serum leptin and PPTG levels were measured longitudinally till 26 weeks in Wistar rats fed on controlled diet (group 1) and high sucrose diet (HSD) (group 2). Two additional groups fed on HSD were taken and treated with pioglitazone (group 3) and atorvastatin (group 4). Body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose intolerance were also measured during this period. Comparison of the groups were done and Pearson's correlation coefficient was used to ascertain the association. Results: Leptin levels were significantly higher in all three groups receiving HSD compared to controlled diet group from week 2 to week 26 (P < 0.01). The postprandial triglyceride area under the curve (PPTG AUCs) were significantly higher in group 2 than controls during this period (P < 0.001). Body weight, HOMA-IR and glucose AUC were found to be significantly higher in group 2 rats than controls only from week 6, 8, and 12 respectively. In HSD-fed rats, but not in control, mean serum leptin levels from 2-26 weeks as well as peak (10th week) and 26th week were strongly associated with corresponding as well as preceding PPTG levels. Leptin levels significantly predicted HOMA-IR and prediabetes in group 2. Conclusion: This study found significant hyperleptinemia associated with postprandial hypertriglyceridemia that predicted insulin resistance and prediabetes in high sucrose diet-fed rats.

Essential amino acid profiling of the four lac hosts belonging to genus Flemingia: its implications on lac productivity.

The Indian lac insect (Kerria lacca), a hemipteran, phloem sap sucking sedentary insect is an important bioresource which thrives on tender twigs of more than 400 plant species belonging to various genera and families. The most common commercial host plants for lac cultivation are big trees hence cultivation was concentrated mainly to dense forests across the country till last decade. Recently, a new bushy host plant belonging to the genus Flemingia has been introduced so that lac can be cultivated on farmlands like other cash crops. The insect is sedentary and feeds on the phloem sap of the host plants, the only source of its nutrition. Interestingly, the biological attributes of the insect as well as the qualitative and quantitative production of lac is influenced by the host plant on which the insect feeds upon. The present study was thus aimed at deciphering the effect of phloem sap constituents obtained from four plant host taxa belonging to the same genus Flemingia viz. F. semialata, F. macrophylla, F. bracteata and F. chapar (essential amino acids only-EAAs) on lac productivity. Moreover, a newer method for phloem sap collection i.e. Dot-blot in addition to the facilitated exudation using EDTA was also investigated. Dot-blot method for phloem sap collection also came out to be a promising method for field studies; although slightly higher concentration of EAAs were obtained from EDTA method, thus the later was used for further analysis. Phloem sap of four plant host taxa belonging to the same genus Flemingia were qualitatively and quantitatively analysed for seven EAAs (Arginine, Glycine, Leucine, Methionine, Phenylalanine Tyrosine and Valine). Amino acid concentration regime and further analysis done using statistical tools (ANOVA and PCA) points out the EAA concentration in the phloem sap is in congruency with the lac production data obtained through previous studies as F. semialata > F. macrophylla > F. chapar > F. bracteata. The present study thus scientifically points out that F. semialata can be a promising plant for lac cultivation on the basis of higher EAA content as compared to the rest three.

Sleep apnea detection from ECG using variational mode decomposition.

Sleep apnea is a pervasive breathing problem during night sleep, and its repetitive occurrence causes various health problems. Polysomnography is commonly used for apnea screening which is an expensive, time-consuming, and complex process. In this paper, a simple but efficient technique based on the variational mode decomposition (VMD) for automated detection of sleep apnea from single-lead ECG is proposed. The heart rate variability and ECG-derived respiration signals obtained from ECG are decomposed into different modes using the VMD, and these modes are used for extracting different features including spectral entropies, interquartile range, and energy. The principal component analysis is employed to reduce the dimension of the feature vector. The experiments are conducted using the Apnea-ECG dataset, and the classification performance of various classifiers is investigated. In per-segment classification, an accuracy of about 87.5% (Sens: 84.9%, Spec: 88.2%) is achieved using the K-nearest neighbor classifier. In per-recording classification, the proposed technique using the linear discriminant analysis model outperformed the existing apnea detection approaches by achieving the accuracy of 100%. The algorithm also provided the best agreement between the estimated and reference apnea-hypopnea index (AHI) values. These results show that the algorithm has the potential to be used for home-based apnea screening systems.

Translating Fear Circuitry: Amygdala Projections to Subgenual and Perigenual Anterior Cingulate in the Macaque.

Rodent fear-learning models posit that amygdala-infralimbic connections facilitate extinction while amygdala-prelimbic prefrontal connections mediate fear expression. Analogous amygdala-prefrontal circuitry between rodents and primates is not established. Using paired small volumes of neural tracers injected into the perigenual anterior cingulate cortex (pgACC; areas 24b and 32; a potential homologue to rodent prelimbic cortex) and subgenual anterior cingulate cortex (sgACC, areas 25 and 14c; a potential homologue to rodent infralimbic cortex) in a single hemisphere, we mapped amygdala projections to the pgACC and sgACC within single subjects. All injections resulted in dense retrograde labeling specifically within the intermediate division of the basal nucleus (Bi) and the magnocellular division of the accessory basal nucleus (ABmc). Areal analysis revealed a bias for connectivity with the sgACC, with the ABmc showing a greater bias than the Bi. Double fluorescence analysis revealed that sgACC and pgACC projections were intermingled within the Bi and ABmc, where a proportion were double labeled. We conclude that amygdala inputs to the ACC largely originate from the Bi and ABmc, preferentially connect to the sgACC, and that a subset collaterally project to both sgACC and pgACC. These findings advance our understanding of fear extinction and fear expression circuitry across species.

Clinical Profile, Risk Factors and Outcomes in Patients with Cerebral Venous Sinus Thrombosis: A Study from Western India.

AIM: Study of cause and clinical profile of venous sinus thrombosis in Western India. SETTINGS AND DESIGN: A retrospective study was conducted to ascertain the clinical profile, etiology, and follow up of patients with venous sinus thrombosis. METHODS AND MATERIAL: Hospital database of patients suffering from venous sinus thrombosis from two tertiary care hospitals in West India were studied. A telephonic follow up was taken for assessment of outcome. Inclusion criteria were a) Age more than 15 years of age b) clinically symptomatic patients c) Diagnosis confirmed by Magnetic resonance Venography (MRV) or CT Venography (CT Venography) Exclusion criteria: Patients with infarct in arterial territory, hypertensive hemorrhage, metabolic encephalopathy and eclampsia were excluded from the study. STATISTICAL ANALYSIS USED: Descriptive statistic was performed as frequency, mean and standard deviation or percentages. Difference in continuous variables was evaluated by using independent t-test while chi-square test was performed in categorical variables. Statistical P<0.05 was considered statistically significant. RESULTS: We conducted a retrospective study of patients with venous sinus thrombosis in Rajasthan in western India. Out of 71 patients in our study group the mean age of presentation was 36.64 years. 42 patients were male (59.2%) and 29 were female (40.8%). Only 9 patients (12.6%) had pregnancy or puerperium related venous sinus thrombosis. The most common presenting feature was headache 47/71(66.2), followed by seizures 33 (46.5%), paresis 20/71 (28.16%) and coma 15/71(21.1%). MRI Brain recorded infarcts in 32/71 patients and predominant hemorrhage was recorded in 34/71. 4 cases were associated with malignancy (one CNS, one outside CNS and 2 hematological). Raised homocysteine level was found in 26/35 (74.3%) patients in whom they were measured. 9 patients had moderately elevated homocysteine levels (15-30), another 9 had intermediate values (31-64) and 5 patients had elevated homocysteine level >65. Hyperhomocysteinemia was the commonest causative factor and was far more common in men (21/25) than in women (5/10). (p value 0.019). 24 out of 71 patients were found to be anemic (33.8%). Anemia was far more common in women than in men. (p value .002). Protein C level was found abnormal in 5/27 patients, Protein S in 6/27 patients and Anti thrombin III in 1/23 patient studied respectively. History of oral contraceptive intake was recorded in only a minority of women with venous sinus thrombosis 7(24.1%) compared to the western data where most of the venous sinus thrombosis are related to the contraceptive pills. CONCLUSION: The clinical presentation of venous sinus thrombosis in tertiary care centers is changing outside the traditional peurperium / pregnancy related venous sinus thrombosis. Common risk factors include hyperhomocysteinemia, anemia, coagulopathy, pregnancy related, vasculitis, malignancy and oral contraceptive usage. Male involvement was far more common than females and was usually associated with a higher level of homocysteine.

Detection of Wolbachia Phage (WO) in Indian Lac Insect [Kerria lacca (Kerr.)] and Its Implications.

Wolbachia, a maternally inherited bacterium induces reproductive alterations in its hosts such as feminization of males, male killing and parthenogenesis. It is the most diverse endosymbiont infecting more than 70% of the insects ranging from pests to pollinators. Kerria lacca-a hemipteran is a sedentary, oriental insect known to produce lac-the only resin of animal origin. The present study was conducted to screen the presence of Wolbachia and its associated phages in the two infrasubspecific forms (four insect lines) of K. lacca viz. kusmi and rengeeni differing from each other on the basis of host preference. Wolbachia and its associated phage were found to be prevalent in all the insect lines analyzed. We, hereby, report the presence of WO-phage (Wolbachia phage) for the first time in K. lacca. Further, phylogenetic data differentiated the kusmi and rengeeni infrasubspecific forms into two different groups on the basis of WO-phage sequences.

Molecular modeling and docking of recombinant HAP-phytase of a thermophilic mould Sporotrichum thermophile reveals insights into molecular catalysis and biochemical properties.

A thermostable and protease-resistant HAP-phytase of Sporotrichum thermophile was over-expressed in Pichia pastoris X-33. Purified recombinant phytase displayed all its biochemical properties similar to wild type. Molecular modeling and docking of phytase with various substrates showed differential binding patterns with GoldScore values ranging from 40.61 to 79.78. Docking with different substrates revealed strong binding affinity with ATP and phytic acid, while the lowest with AMP and phosphoenol pyruvate. This was further confirmed using biochemical assays, as the recombinant enzyme displayed broad substrate specificity. Docking with inhibitors also showed differential binding with GoldScore values ranging from 22.94 (2,3-butanedione) to 85.72 (myo-inositol hexasulphate). Validation using biochemical analysis revealed that both 2,3-butanedione and phenyl glyoxal inhibited the phytase activity significantly. Furthermore, presence of inorganic phosphate in the reaction mixture also inhibited the phytase activity, as there was no activity at and beyond 0.8 mM. Docking of phytase with metavanadate showed binding at the same atom in the active-site where the substrate i.e. phytic acid binds. Vanadium incorporation resulted in the catalytic conversion of phytase into a peroxidase with concomitant inhibition of phytase activity. Peroxidase activity was high in acidic range and the product formation showed correlation with reaction time. Furthermore, molecular modeling and docking of recombinant HAP-phytase of a thermophilic mould S. thermophile reveals insights into molecular catalysis that is validated by the biochemical properties.

ECG-derived respiration based on iterated Hilbert transform and Hilbert vibration decomposition.

Monitoring of the respiration using the electrocardiogram (ECG) is desirable for the simultaneous study of cardiac activities and the respiration in the aspects of comfort, mobility, and cost of the healthcare system. This paper proposes a new approach for deriving the respiration from single-lead ECG based on the iterated Hilbert transform (IHT) and the Hilbert vibration decomposition (HVD). The ECG signal is first decomposed into the multicomponent sinusoidal signals using the IHT technique. Afterward, the lower order amplitude components obtained from the IHT are filtered using the HVD to extract the respiration information. Experiments are performed on the Fantasia and Apnea-ECG datasets. The performance of the proposed ECG-derived respiration (EDR) approach is compared with the existing techniques including the principal component analysis (PCA), R-peak amplitudes (RPA), respiratory sinus arrhythmia (RSA), slopes of the QRS complex, and R-wave angle. The proposed technique showed the higher median values of correlation (first and third quartile) for both the Fantasia and Apnea-ECG datasets as 0.699 (0.55, 0.82) and 0.57 (0.40, 0.73), respectively. Also, the proposed algorithm provided the lowest values of the mean absolute error and the average percentage error computed from the EDR and reference (recorded) respiration signals for both the Fantasia and Apnea-ECG datasets as 1.27 and 9.3%, and 1.35 and 10.2%, respectively. In the experiments performed over different age group subjects of the Fantasia dataset, the proposed algorithm provided effective results in the younger population but outperformed the existing techniques in the case of elderly subjects. The proposed EDR technique has the advantages over existing techniques in terms of the better agreement in the respiratory rates and specifically, it reduces the need for an extra step required for the detection of fiducial points in the ECG for the estimation of respiration which makes the process effective and less-complex. The above performance results obtained from two different datasets validate that the proposed approach can be used for monitoring of the respiration using single-lead ECG.

Persistence of thiacloprid and deltamethrin residues in tea grown at different locations of North-East India.

In order to examine the residues of thiacloprid (90 and 180 g a.i./ha) and deltamethrin (10 and 20 g a.i./ha) in fresh tea leaves, made tea and tea infusion, field experiments were conducted at three different locations viz. Kamalpur tea estate, Darjeeling; West Bengal, Teok tea Estate and AAU, Jorhat; Assam in India. Regardless of location and doses, residues of both the insecticides dissipated following first order kinetics. The half-life of Thiacloprid (4.93-5.38 days) was longer than that of deltamethrin (1.78-1.94 days). Processing of green tea leaves reduced the residue level of thiacloprid and deltamethrin in made tea. No residues of both these insecticides could be detected in tea infusion. With respect to the phenolic distribution in tea, a marked increase in total catechin monomers with thiacloprid and greater accumulation of EGCG and ECG (indices of phenol quality) with deltamethrin were observed.

Persistence, dissipation and consumer risk assessment of a combination formulation of flubendiamide and deltamethrin on cucumber.

Multi-location supervised field trials were conducted in India at four locations of the All India Network Project (AINP) on Pesticide Residues to study the persistence, dissipation and risk assessment of flubendiamide and deltamethrin on cucumber (Cucumis sativus). Residues of flubendiamide and deltamethrin on cucumber resulting from three spray applications of a combination formulation (flubendiamide 90% + deltamethrin 60%, 150 SC) at recommended (22.5 + 15 g a.i./ha) and double the recommended (45 + 30 g a.i./ha) dose were analysed. On the basis of persistence and dissipation studies, the half- life (T1/2) of flubendiamide on cucumber varied from 1.40 to 2.98 (recommended dose) and 1.55 to 2.76 days (double the recommended dose), while that of deltamethrin ranged from 2.5 to 4.9 (recommended dose) and 2.7 to 3.9 days (double the recommended dose) at the four locations. On the basis of supervised field trial data and using OECD calculator, MRLs in the combination product of 3 mg kg-1 for flubendiamide and 1.5 mg kg-1 for deltamethrin has been proposed for consideration by the Food Safety and Standards Authority of India (FSSAI). Codex, EU and EPA have fixed MRL of 0.2 mg kg-1 for flubendiamide and deltamethrin.

Multilocation field trials for risk assessment of a combination fungicide Fluopicolide + Propamocarb in tomato.

Dissipation kinetics of two systemic fungicides, namely fluopicolide and propamocarb used as a combination formulation (Infinito 68.75 SC), were studied on tomato at four different locations by the All India Network Project on Pesticide Residues to recommend their pre-harvest interval (PHI) and to propose the maximum residue limits (MRL) for the two fungicides based on chronic hazard exposure assessment. The combination fungicide was sprayed thrice at the recommended dosage of 93.75 g a.i./ha fluopicolide and 937.50 g a.i./ha propamocarb as well as at double the recommended dosage of 187.50 g a.i./ha fluopicolide and 1875.0 g a.i./ha propamocarb on tomato crops and the residues were monitored periodically by GC-MS. The fungicides dissipated to below the limit of quantification (LOQ) within 10 to 15 days, with a half-life of 2-4 days for fluopicolide and 1-2 days for propamocarb. Taking into consideration the MRLs of codex and calculations made using the method of MRL fixation of the Food Safety and Standard Authority of India (FSSAI) as well as the Organization for Economic Co-operation and Development (OECD) calculator, MRL of 5 mg/kg is proposed for fluopicolide and 15 mg/kg for propamocarb, following critical exposure of the commodity considering PHI of 1 day.

An algorithm for sleep apnea detection from single-lead ECG using Hermite basis functions.

This paper introduces a methodology for the detection of sleep apnea based on single-lead electrocardiogram (ECG) of the patient. In the proposed technique, each QRS complex of the ECG signal is approximated using a linear combination of the lower order Hermite basis functions. The coefficients of the Hermite expansion are then used to discriminate the apnea and normal segments along with three features based on R-R time series (mean of R-R intervals, the standard deviation of R-R intervals) and energy in the error of the QRS approximation. To perform classification between the apnea and normal segments, four different types of classifiers (K-nearest neighbor (KNN), multilayer perceptron neural network (MLPNN), support vector machine (SVM), and least-square support vector machine (LS-SVM)) are used in this work. In total, 70 ECG recordings from Apnea-ECG dataset are used in this study and the performance of the proposed algorithm is evaluated based on the minute-by-minute (per-segment) classification, and per-recording (where the entire ECG recording of a subject is discriminated as the apnea or normal one) classification. By considering the events of apnea and hypopnea together, an accuracy of about 84% is achieved on the minute-by-minute basis classification using the LS-SVM classifier with the Gaussian radial basis function (RBF) kernel. On the other hand, an accuracy of about 97.14% is achieved for per-recording classification using the SVM, and LS-SVM classifiers. From the results, it is observed that the proposed methodology provides comparable accuracy with the methods existing in the literature at reduced computational cost due to the lesser number of features selected for the classification.