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Background/aims Menopause can cause drastic changes that trigger severe symptoms in women and, in turn, influence their quality of life. Many women no longer prefer hormone replacement therapy because of its potential adverse effects. Hence, it is crucial to establish alternate interventions to alleviate menopausal symptoms. The aim of this study was to estimate the relationship between quality of life and level of physical activity in menopausal women. Methods A total of 260 postmenopausal women were recruited in this cross-sectional study. The Menopause Rating Scale and International Physical Activity Questionnaire – Short Form were used to assess quality of life and physical activity respectively. Results Women with higher levels of physical activity had fewer total menopausal, somato-vegetative and psychological symptoms (PConclusions Women with low physical activity levels presented with greater menopausal symptoms. Regular physical activity can be recommended to alleviate symptoms following menopause, thereby improving quality of life.

Capparis decidua is used in the traditional system of medicine used due to its medicinal properties. Selenium nanoparticle was synthesized in a simple and rapid way by green synthesis method. Selenium nanoparticle was synthesized using aqueous extract of Capparis decidua fruit. The aim of this present study is to synthesize and to analyse the characterization of selenium nanoparticle synthesized using Capparis decidua. Characterization of selenium nanoparticle was done using ultra-visible spectroscopy and Transmission electron microscope [TEM]. Initially, the wavelength obtained for synthesized selenium nanoparticles ranged from 300nm to 600nm. Then TEM was carried out to find the size and shape of the nanoparticle. The selenium nanoparticle was spherical in shape with size of 320nm. The present study concluded that the selenium nanoparticle prepared using Capparis decidua was ecofriendly and may serve and benefit the society because of its rich medicinal property with less side effects if further research is carried out.

Introduction HIV Sentinel Surveillance (HSS) among pregnant women is a key indicator to estimate the HIV prevalence in the general population, as nearly 85% of HIV transmission in India is linked to the heterosexual route. Tracking the levels and trends of the HIV prevalence at state, regional, and district levels help to prioritize and facilitate a tailor-made intervention. Here, we analyze the region and district-wise levels and trends of HIV prevalence among pregnant women attending the antenatal clinics (ANC) from 2003 to 2019 in Tamil Nadu. Methods Eleven rounds of HSS data collected from pregnant women in Tamil Nadu, from 2003 to 2019 were analysed. Consistent sites were grouped into four geographical regions (North, Central, West and South), a total of 67 sites including 33 urban 31 rural, and 3 private sites. Chi-square trend test used to find linear trends and spatial analysis used to understand the geographical distribution of HIV prevalence over the years. Results In total, 2,77,444 blood samples were collected during HSS from 2003 to 2019. In 2019, the state HIV prevalence was 0.18 (95% CI: 0.13–0.23); region-wise prevalence was 0.21, 0.07, 0.32 and 0.12 in North, Central, West and South respectively. HIV prevalence in Tamil Nadu had significantly declined since 2003, which however, was not significant in all districts; with inter-district fluctuations. Conclusion HIV interventions have to be strengthened in the districts with inconsistent trends, specifically the West region. This requires a more detailed analysis of region-specific contextual factors associated with the transmission risk.

Background HIV Sentinel Surveillance among pregnant women attending antenatal care clinics, ANC-HSS, is used to estimate HIV prevalence among the general population. Despite the declining trend, HIV prevalence among the general population in Karnataka is still higher than the national average (0.22%), with a recent, noticeable stabilization. Demographic analysis on concentrated HIV infection among pregnant women could be potential indicators for targeted HIV interventions among general population as well as and prevention of parent to child transmission (PPTCT). Objectives To analyse the demographics of HIV-positive pregnant mothers in Karnataka, thereby identifying the most-at-risk populations (MARP) within the general population. Methods In total, 24800 eligible pregnant women aged 15–49 attending the ANC clinic for the first time during the surveillance period (Jan–Mar, 2017) were enrolled. Demographic data and blood samples were collected, recorded and tested for HIV. Age-specific factors associated with HIV prevalence, besides the demographics of the HIV positive pregnant women, were analysed to identify the MARP for targeted HIV interventions. Results Comprehensively, none of the demographic factors was significantly associated with HIV prevalence. Nevertheless, analysis of demographics, HIV test history and ART status of HIV-positive pregnant women reveals prominent prevalence patterns. The epidemic was majorly confined within young, less educated, primigravida and rural mothers of low economic status. Conclusion ANC-HSS is designed to estimate the HIV prevalence among general population at national, state and district levels and is not reflective of the concentrated epidemic confined to MARP. Identifying the disease pattern specific to MARP is essential for effective targeted interventions and disease management.

BACKGROUND Hearing loss is a chronic condition, and many cases can be detected in the neonatal period. Recognizing it early is of crucial importance as early auditory rehabilitation would help in child’s comprehensive development. We wanted to assess the prevalence of hearing impairment among high risk newborns admitted to inborn unit of tertiary care centre in Central Kerala and screen for the associated risk factors in these newborns. METHODS Thousand consecutive inborn neonates from Neonatal ICU, Department of Paediatrics, tertiary care centre in Thrissur, Kerala, detected as high risk by Joint Committee on Infant Hearing (JCIH) criteria were enrolled for the study from December 2011 to November 2012 after the approval by Institute’s Ethics Review Board. Risk factor assessment was done before enrolment. A qualified audiologist conducted the test on babies in soundproof chamber. DPOAEs (Distortion Product Otoacoustic Emissions) were used for initial testing after checking ears for debris. Those who failed in the first test were asked to come for a retest after 2 weeks. Those who failed in the retest were asked to report for Brainstem Evoked Response Audiometry (BERA). Those who were diagnosed as having hearing impairment were advised auditory rehabilitation as well as auditory verbal therapy. RESULTS Of the 1000 eligible neonates born in our hospital during the study period (December 2011 to November 2012) 69 were lost to follow up. Among the remaining 931 babies the frequency of hearing impairment was 0.8 %. Among the 931 neonates, 130 had absent response with the first OAE test contributing to 13.9 %. Twenty-one neonates had absent response to second OAE test out of 130 contributing to 16.1 %. The failure rate for second test is 2.2 % of the total population of 931 newborns. Eight of the 21 neonates who were subjected to BERA had severe hearing loss. The prevalence of hearing impairment was 8 per 1000. CONCLUSIONS The prevalence (percentage) of hearing impairment by two staged screening protocol is 0.8 %. Risk factors which were present in these babies were prematurity, low birth weight, low Apgar score, history of exanthematous fever in mother, neonatal jaundice, ototoxic medication history, craniofacial anomalies, and family history of deafness, meningitis and mechanical ventilation. KEYWORDS Otoacoustic Emissions, Brain Stem Evoked Response Audiometry, Risk Factors, Hearing Impairment, Neonates

Hepatocellular carcinoma (HCC) is a heterogeneous inflammation-driven malignancy, which, despite significant advances in management, continues to portend a poor prognosis. Recent advances in basic and translational research have increasingly defined the role of the tumor microenvironment in the development and progression of HCC and facilitated the development of novel molecular targets. The hepatoma microenvironment is characterised by an immunosuppressive milieu of immune cells and tumor vasculature that is both structurally and functionally abnormal. Normalising the tumor microenvironment by adopting a multipronged approach that targets both carcinogenic processes and the immunosuppressive milieu has been supported by pre-clinical and clinical data. In this review, we summarise the current understanding of the hepatoma microenvironment, its influences and dynamic interactions with tumor cells, the vasculature and the gut. Finally, we discuss how manipulating the tumor microenvironment continues to shape the evolving landscape of HCC therapy.

Background and Objectives: The purpose of this study was to analyze trends in HIV prevalence and risk factors associated with HIV infection among pregnant women attending antenatal clinics in Odisha State, India. Methods: Data were from the HIV Sentinel Surveillance (HSS) among pregnant women, a descriptive cross-sectional study using consecutive sampling method and conducted in India. Data and samples were collected from pregnant women attending select antenatal clinics that act as designated sentinel sites in Odisha State, India, during the three months surveillance period and in three surveillance years: 2013, 2015, and 2017. All eligible pregnant women aged between 15 and 49 years, attending the sentinel sites for the first time during the surveillance period, were included. Information on their socio-demographic characteristics and blood samples were also collected. Results: In total, 38,384 eligible pregnant women were included in the survey. Of these, 107 women were HIV positive, with an overall prevalence of 0.28%. HIV prevalence indicated a stabilizing trend between 2013 and 2017. However, pregnant women whose spouses were non-agricultural laborers, truck drivers, or migrants were significantly at higher risk of being infected. Likewise, HIV prevalence significantly increased over the years among pregnant women whose spouses were in the service sector (government or private). District-wise fluctuations in HIV prevalence was observed, with the district of Cuttack recording the highest prevalence among the districts. Conclusion and Global Health Implications: Women who are spouses of non-agricultural laborers, truck drivers or migrants need focused interventions, such as creating awareness on HIV and its prevention. Migration, due to poverty and its impact on sexually transmitted diseases among migrants from low and middle-income countries, have been documented globally. Single male migrant specific interventions are recommended to halt the disease progression among pregnant women and general population in Odisha, India. Key words: • HIV sentinel surveillance • Pregnant women • HIV prevalence • Socio-demographic factor • Odisha • India Copyright © 2020 Santhakumar et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unre-stricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

The progress towards the development of a nucleoside analogue with inhibitory properties against SETDB1, a histone methyltransferase (HMT), is described. Based on the structure of the natural cofactor S-adenosyl-L-methionine (SAM), novel fluorinated nucleoside analogues were synthesized. Two of these compounds bearing a C2′-F and C5′-primary amine moiety showed moderate inhibition of SETDB1, a lysine HMT for which there is only one reported inhibitor.

This study tests the use of a constrained nonnegative matrix factorization (NMF) algorithm to explore the comparatively new field of chemometric microscopy to support tissue diagnosis. The algorithm can extract the spectral signature and the absolute concentration map of endogenous fluorophores from wide-field microscopic images. The resultant data distinguished normal and fibrous calvarial tissues, based on the changes in their spectral signatures. The absolute concentration map of endogenous fluorophores, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), and lipofuscin were derived from microscopic images and compared with the fluorescence from pure fluorophores. While the absolute concentration of NADH increased, the same of FAD and lipofuscin decreased from a normal to fibrous calvarial condition. An increase in the optical redox ratio, possibly due to the metabolic changes during the development of fibrosis, was observed. Differentiating tissue types using the absolute concentration map was found to be considerably more precise than that achievable with relative concentration. The quantification of fluorophores with reference to the absolute concentration map can eliminate uncertainties due to system responses or measurement details, thereby generating more biologically apposite data. Wide-field microscopy augmented with a constrained NMF algorithm could emerge as an advanced diagnostic tool, potentially heralding the emergence of chemometric microscopy.

Cortical ependymomas are uncommon lesions. We report a cortical ependymoma displaying an unusual imaging pattern. The lesion demonstrated a T1 hyperintense rim and limited perilesional edema but lacked contrast enhancement. T1 hyperintense rim and stalk-like ventricular extension of FLAIR hyperintensity have previously been considered pathognomonic of angiocentric glioma. Hence, we conclude that the radiologists should be aware of this uncommon imaging pattern of cortical ependymoma. The condition warrants prompt surgical management in view of the increased potential for higher grade transformation, unlike grade I roman numeral may be given angiocentric gliomas.

The adaptive immune response could play a major role in the resolution of lung injury. Although regulatory T cells (Tregs) have been implicated in promoting the resolution of lung injury, therapeutic strategies to enhance Treg quantity and activity at the site of injury need further exploration. In the current study, Akt inhibition using triciribine (TCBN), given 48 h after lipopolysaccharide (LPS) administration, increased Tregs-promoted resolution of acute lung injury (ALI). TCBN treatment enhanced the resolution of LPS-induced ALI on day 7 by reducing pulmonary edema and neutrophil activity associated with an increased number of CD4+/FoxP3+/CD103+ and CTLA4+ effector Tregs, specifically in the injured lungs and not in the spleen. Treatment of EL-4 T-lymphocytes with two Akt inhibitors (TCBN and MK-2206) for 72 h resulted in increased FoxP3 expression in vitro. On the other end, Treg-specific PTEN knockout (PTENTreg KO) mice that have a higher Akt activity in its Tregs exhibited a significant impairment in ALI resolution, increased edema, and neutrophil activity associated with a reduced number of CD4+/FoxP3+/CD103+ and CTLA4+ effector Tregs as compared with the control group. In conclusion, our study identifies a potential target for the treatment of late-stage ALI by promoting resolution through effector Treg-mediated suppression of inflammation.

The clinical phenotype of autism spectrum disorder and epilepsy (ASD-E) is a common neurological presentation in various genetic disorders, irrespective of the underlying pathophysiological mechanisms. Here we describe the demographic and clinical profiles, coexistent neurological conditions, type of seizures, epilepsy syndrome, and EEG findings in 11 patients with ASD-E phenotype with proven genetic etiology. The commonest genetic abnormality noted was CDKL5 mutation (3), MECP2 mutation (2), and 1p36 deletion (2). The median age of onset of clinical seizures was 6 months (range, 10 days to 11 years). The most common seizure type was focal onset seizures with impaired awareness, observed in 7 (63.6%) patients followed by epileptic spasms in 4 (30.8%), generalized tonic-clonic and atonic seizures in 3 (27.3%) patients each and tonic seizures in 2 (18.2%) patients and myoclonic seizures in 1 (9.1%) patient. Focal and multifocal interictal epileptiform abnormalities were seen in 6 (54.6%) and 5 (45.5%) patients, respectively. Epileptic encephalopathy and focal epilepsy were seen in 7 (63.6%) and 4 (36.4%) patients, respectively. The diagnostic yield of genetic testing was 44% (11 of 25 patients) and when variants of unknown significance and metabolic defects were included, the yield increased to 60% (15 of 25 patients). We conclude that in patients with ASD-E phenotype with an underlying genetic basis, the clinical seizure type, epilepsy syndrome, and EEG patterns are variable. Next-generation exome sequencing and chromosomal microarray need to be considered in clinical practice as part of evaluation of children with ASD-E phenotype.

Objective Traumatic brain injury is a major risk factor for acquired epilepsies, and understanding the mechanisms underlying the early pathophysiology could yield viable therapeutic targets. Growing evidence indicates a role for inflammatory signaling in modifying neuronal excitability and promoting epileptogenesis. Here we examined the effect of innate immune receptor Toll-like receptor 4 (TLR4) on excitability of the hippocampal dentate gyrus and epileptogenesis after brain injury. Methods Slice and in vivo electrophysiology and Western blots were conducted in rats subject to fluid percussion brain injury or sham injury. Results The studies identify that TLR4 signaling in neurons augments dentate granule cell calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (CP-AMPAR) currents after brain injury. Blocking TLR4 signaling in vivo shortly after brain injury reduced dentate network excitability and seizure susceptibility. When blocking of TLR4 signaling after injury was delayed, however, this treatment failed to reduce postinjury seizure susceptibility. Furthermore, TLR4 signal blocking was less efficacious in limiting seizure susceptibility when AMPAR currents, downstream targets of TLR4 signaling, were transiently enhanced. Paradoxically, blocking TLR4 signaling augmented both network excitability and seizure susceptibility in uninjured controls. Despite the differential effect on seizure susceptibility, TLR4 antagonism suppressed cellular inflammatory responses after injury without impacting sham controls. Interpretation These findings demonstrate that independently of glia, the immune receptor TLR4 directly regulates post-traumatic neuronal excitability. Moreover, the TLR4-dependent early increase in dentate excitability is causally associated with epileptogenesis. Identification and selective targeting of the mechanisms underlying the aberrant TLR4-mediated increase in CP-AMPAR signaling after injury may prevent epileptogenesis after brain trauma. ANN NEUROL 2020;87:497-515.

Altered Synaptic Drive Onto Birthdated Dentate Granule Cells in Experimental Temporal Lobe Epilepsy Althaus AL, Moore SJ, Zhang H, Du Plummer X, Murphy GG, Parent JM. J Neurosci. 2019;39(38):7604-7614. doi:10.1523/JNEUROSCI.0654-18.2019.Dysregulated adult hippocampal neurogenesis occurs in many temporal lobe epilepsy (TLE) models. Most dentate granule cells (DGCs) generated in response to an epileptic insult develop features that promote increased excitability, including ectopic location, persistent hilar basal dendrites (HBDs), and mossy fiber sprouting. However, some appear to integrate normally and even exhibit reduced excitability compared to other DGCs. To examine the relationship between DGC birthdate, morphology, and network integration in a model of TLE, we retrovirally birth-dated either early-born (postnatal day 7) or adult-born (postnatal day 60) DGCs. Male rats underwent pilocarpine-induced status epilepticus (SE) or sham treatment at postnatal day 56. Three to six months after SE or sham treatment, we used whole-cell patch clamp and fluorescence microscopy to record spontaneous excitatory and inhibitory currents from birth-dated DGCs. We found that both adult-born and early-born populations of DGCs recorded from epileptic rats received increased excitatory input compared with age-matched controls. Interestingly, when adult-born populations were separated into normally integrated (normotopic) and aberrant (ectopic or HBD containing) subpopulations, only the aberrant populations exhibited a relative increase in excitatory input (amplitude, frequency, and charge transfer). The ratio of excitatory to inhibitory input was most dramatically upregulated for ectopically localized DGCs. These data provide definitive physiological evidence that aberrant integration of post-SE, adult-born DGCs contributes to increased synaptic drive and supports the idea that ectopic DGCs serve as putative hub cells to promote seizures.Significance Statement:Adult DGC neurogenesis is altered in rodent models of TLE. Some of the new neurons show abnormal morphology and integration, but whether adult-generated DGCs contribute to the development of epilepsy is controversial. We examined the synaptic inputs of age-defined populations of DGCs using electrophysiological recordings and fluorescent retroviral reporter birth-dating. Dentate granule cells generated neonatally were compared with those generated in adulthood, and adult-born neurons with normal versus aberrant morphology or integration were examined. We found that adult-born, ectopically located DGCs exhibit the most pro-excitatory physiological changes, implicating this population in seizure generation or progression. Targeting Seizure-Induced Neurogenesis in a Clinically Relevant Time Period Leads to Transient But Not Persistent Seizure Reduction Varma P, Brulet R, Zhang L, Hsieh J. J Neurosci. 2019;39(35):7019-7028. doi:10.1523/JNEUROSCI.0920-19.2019.Mesial temporal lobe epilepsy (mTLE), the most common form of medically refractory epilepsy in adults, is usually associated with hippocampal pathophysiology. Using rodent models of mTLE, many studies including work from our laboratory have shown that new neurons born around the onset of severe acute seizures known as status epilepticus (SE) are crucial for the process of epileptogenesis and targeting seizure-induced neurogenesis either genetically or pharmacologically can impact the frequency of chronic seizures. However, these studies are limited in their clinical relevance as none of them determines the potential of blocking new neurons generated after the epileptogenic insult to alleviate the development of chronic seizures. Therefore, using a pilocarpine-induced SE model of mTLE in mice of either sex, we show that >4 weeks of continuous and concurrent ablation of seizure-induced neurogenesis after SE can reduce the formation of spontaneous recurrent seizures by 65%. We also found that blocking post-SE neurogenesis does not lead to long-term seizure reduction as the effect was observed only transiently for 10 days with >4 weeks of continuous and concurrent ablation of seizure-induced neurogenesis. Thus, these findings provide evidence that seizure-induced neurogenesis when adequately reduced in a clinically relevant time period has the potential to transiently suppress recurrent seizures, but additional mechanisms need to be targeted to permanently prevent epilepsy development.Significance Statement:Consistent with morphological and electrophysiological studies suggesting aberrant adult-generated neurons contribute to epilepsy development, ablation of seizure-induced new neurons at the time of the initial insult reduces the frequency of recurrent seizures. In this study, we show that continuous targeting of post-insult new neurons in a therapeutically relevant time period reduces chronic seizures; however, this effect does not persist suggesting possible additional mechanisms.

The ongoing COVID-19 pandemic has forced every radiology set-up to evolve and formulate guidelines for day-to-day functioning. The sub-speciality of neuroradiology, both diagnostic and neuro-intervention, forms a very important part of any radiology or ‘neuro-care’ set-up. The present document is a consensus statement of the Indian Society of Neuroradiology, prepared after reviewing the available data and working experience. It scientifically tries to answer many questions faced by neuroradiologists everyday in practice. It encompasses simple things such as which patients need to be imaged, what precautions are essential, the work-flows, cleaning of radiology equipment, how to carry out neuro-interventions in COVID-suspect patients, and what procedures/tests to avoid, or their alternatives, to minimise the spread of COVID infection both to the patients and health care personnel. As radiology set-ups can be large, every sub-speciality may have certain precautions which will not be covered in general guidelines, and this document tries to answer those for neuroradiologists. Carefully evolved Standards of Operating Procedure (SOPs) and guidelines are the need of the hour to guide in providing uninterrupted and adequate services to the needy without compromising the safety of the specialised work force and facilities involved.

Cereal bioactive compounds, especially polyphenols, are known to possess a wide range of disease preventive properties that are attributed to their antioxidant and anti-inflammatory activity. However, due to their low plasma concentrations after oral intake, there is controversy regarding their therapeutic benefits in vivo. Within the gastrointestinal tract, some cereal polyphenols are absorbed in the small intestine, with the majority accumulating and metabolised by the colonic microbiota. Chemical and enzymatic processes occurring during gastrointestinal digestion modulate the bioactivity and bioaccessibility of phenolic compounds. The interactions between the cereal polyphenols and the intestinal epithelium allow the modulation of intestinal barrier function through antioxidant, anti-inflammatory activity and mucin production thereby improving intestinal health. The intestinal microbiota is believed to have a reciprocal interaction with polyphenols, wherein the microbiome produces bioactive and bioaccessible phenolic metabolites and the phenolic compound, in turn, modifies the microbiome composition favourably. Thus, the microbiome presents a key link between polyphenol consumption and the health benefits observed in metabolic conditions in numerous studies. This review will explore the therapeutic value of cereal polyphenols in conjunction with their bioaccessibility, impact on intestinal barrier function and interaction with the microbiome coupled with plasma anti-inflammatory effects.

Development of brain circuitry requires precise regulation and timing of proliferation and differentiation of neural progenitor cells. The p75 neurotrophin receptor (p75NTR) is highly expressed in the proliferating granule cell precursors (GCPs) during development of the cerebellum. In a previous paper, we showed that proNT3 promoted GCP cell cycle exit via p75NTR. Here we used genetically modified rats and mice of both sexes to show that p75NTR regulates the duration of the GCP cell cycle, requiring activation of RhoA. Rats and mice lacking p75NTR have dysregulated GCP proliferation, with deleterious effects on cerebellar circuit development and behavioral consequences persisting into adulthood. In the absence of p75NTR, the GCP cell cycle is accelerated, leading to delayed cell cycle exit, prolonged GCP proliferation, increased glutamatergic input to Purkinje cells, and a deficit in delay eyeblink conditioning, a cerebellum-dependent form of learning. These results demonstrate the necessity of appropriate developmental timing of the cell cycle for establishment of proper connectivity and associated behavior.SIGNIFICANCE STATEMENTThe cerebellum has been shown to be involved in numerous behaviors in addition to its classic association with motor function. Cerebellar function is disrupted in a variety of psychiatric disorders, including those on the autism spectrum. Here we show that the p75 neurotrophin receptor, which is abundantly expressed in the proliferating cerebellar granule cell progenitors, regulates the cell cycle of these progenitors. In the absence of this receptor, the cell cycle is dysregulated, leading to excessive progenitor proliferation, which alters the balance of inputs to Purkinje cells, disrupting the circuitry and leading to functional deficits that persist into adulthood.

Background The current incidence of obesity and type 2 diabetes is at global epidemic levels. To mitigate their impact, there is a need to develop starch-containing foods that give rise to a low and stable postprandial blood glucose response by increasing the proportion of slowly-digestible and indigestible carbohydrate content. Rice is an ideal target food for such dietary intervention because it is a staple food for over half the world's population. Scope and approach The starch digestion of cooked white rice grains is usually complete or near complete upon consumption, but the rate of digestion is influenced by intrinsic food properties and extrinsic influences. This review provides an overview of the complex interplay between the starch granule and its interaction with non-starch components of the rice grain (intrinsic characteristics) as well as the effects of processing (extrinsic factors) on starch digestibility. Key findings and conclusions The intrinsic properties of white rice grains play a significant role in starch digestibility which can be further enhanced after processing, especially by gelatinisation and retrogradation. Post-harvest storage conditions of rice were found to influence starch digestibility but this effect was temperature-dependent. Limited studies investigated starch-lipid and starch-protein interactions in rice, but changes to substrate accessibility have been implicated. Improving our understanding of the effects of processing on starch digestibility can provide an effective tool for food manufacturers to regulate starch digestibility of existing rice varieties.

Dengue fever is a common viral infection in the tropical areas, especially in India. However, dengue infection presenting as hemorrhagic encephalitis is rare. A 10-year-old girl presented with fever, headache, vomiting, and seizures followed by altered sensorium. Her blood serum was positive for antidengue immunoglobulin M enzyme-linked immunosorbent assay (ELISA) and NS1Ag, and cerebrospinal fluid study showed lymphocytic pleocytosis. Magnetic resonance imaging T2-weighted and fluid-attenuated inversion recovery (FLAIR) images showed hyperintensities involving the bilateral thalami, pons, and midbrain with patchy hemorrhage. Despite all supportive measures, she expired 3 days after admission. Our case highlights that dengue encephalitis may present even in the absence of other classical signs.

Background Motor and non-motor behavior analyses are increasingly utilizied in drug discovery and screening, detection of neurobehavioral disorders and chemical toxicology. The emergence of computational approaches has helped to develop different tools to analyse complex behaviors. Analysis of locomotor behavior helps in understanding the motor neuron disorders like Parkinson’s Disease. Although many animal models are available to study the locomotion, adult zebrafish has emerged as a simple and efficient model to study this behavior. An inexpensive and easily customizable tool is required to replace the licensed and expensive set-up to analyse the locomotor behavior. New method In this study we have optimized the ImageJ plugin wrMTrck to analyse motor and non-motor behaviors in adult zebrafish. We have generated a macro to simplify the preprocessing and tracking. Subsequently, we have developed a data analysis sheet to analyse various behavioral end points. Results We have successfully developed an inexpensive video acquisition set-up and optimized wrMTrck for adult zebrafish. In order to demonstrate the efficacy of this method, adult zebrafish were injected with MPTP and motor and non-motor behaviors were analysed. Expectedly, MPTP injected fish showed decrease in dopamine level and dat expression level, which subsequently led to locomotor behavioral defects as well as anxiety, a non-motor symptom of PD. Comparison with existing method(s) Further, the obtained results were validated by another ImageJ macro developed by Pelkowski et al. (2011) and we observed identical trajectories. Conclusions The usefulness of popular ImageJ plugin wrMTrck and this extended protocol will be helpful to quantify motor and non-motor behavioral parameters.

Oxidative energy metabolism is depressed after mild/moderate traumatic brain injury (TBI) during early development, accompanied by behavioral debilitation and secondary neuronal death. A TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitochondrial modulators and their effects on brain function have shown that kaempferol, a stimulator of the mitochondrial Ca(2+) uniporter channel (mCU), enhanced neural and neurovascular activity in the normal brain and improved stimulus-induced brain activation and behavior after TBI during early development. Because kaempferol enhances mitochondrial Ca(2+) uptake and cycling, with protective effects after TBI, we tested the hypothesis that kaempferol treatment during the acute/subacute stage after TBI (0–72 h) acted on mitochondria in improving TBI outcome. Developmental age rats (P31) underwent TBI and were treated with vehicle or kaempferol (1 mg/kg intraperitoneally) in three doses at 1, 24, and 48 h after TBI. Brains were harvested at 72 h and subjected to liquid chromatography mass spectrometric measurements. Decrease in pyruvate and tricarboxylic acid (TCA) cycle flux were observed in the untreated and vehicle-treated group, consistent with previously established energy metabolic decline after TBI. Kaempferol improved TCA cycle flux, maintained mitochondrial functional integrity as observed by decreased acyl carnitines, improved neural viability as evidenced by higher N-acetyl aspartate levels. The positive outcomes of kaempferol on metabolic profile corresponded with improved sensorimotor behavior.

The control of infections and maintenance of hygienic conditions are of central importance and the insights gained through several investigations have practical significance today. In contrast, the maintenance of environment and surface disinfection is still controversial and demands novel disinfectants to meet the required criteria. The healthcare centers are fraught with various microorganisms and serve as a point source for multidrug resistance in patients which is more critical to treat. Therefore, it has begun a comprehensive plan in hospitals to focus on disinfection and maintenance of hygiene which is not always appreciated. The urgency to determine the effectiveness of disinfectants is often questioned. The review article shows how the existing problems could be solved by a systematic approach and reports on effective evaluation studies that meet the requirements.

Traumatic brain injury (TBI) is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence.(1) Based on the nonlocalized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity, and neurovascular function, are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2 months after injury, using functional MRI (fMRI) and diffusion tensor imaging (DTI). fMRI-based resting-state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus, and thalamus, accompanied by decrease in spatial extent of their corresponding RSFC networks and interhemispheric asymmetry. Cerebrovascular reactivity to arterial CO(2) changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus, and motor cortex. DTI measures of fractional anisotropy and apparent diffusion coefficient, reporting on axonal and microstructural integrity of the brain, indicated similar interhemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus, and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in interhemispheric structural connectivity. Hippocampus, thalamus, and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance, and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

The pathogens which are the effective transmitters of various infections pose a serious problem in restraining their interference in maintaining a sterile environment. The practical applicability of traditional methods of disinfection is restricted due to their cumbersomeness, toxic product generation, and cost-effectiveness. Therefore, the objective of the current review is to elaborate the efficacies and limitations of various novel disinfectants that can show their activity in a few minutes of treatment. The expected outcome would be feasibility for selection of a favorable disinfectant through various technologies that can generate uniform results and form a basis for the true estimation required parameters. Hence, the current paper ends with the consideration of unique new techniques that distinguishes their simplicity, safety, and efficacy in generating a sterile environment.

The development of lifestyle diseases in the obese has been attributed to higher levels of inflammation and free radical mediated oxidative stress. The antioxidant and anti-inflammatory properties of polyphenols in pigmented rice varieties could have potential to neutralize oxidative stress and modulate inflammatory responses in the obese. A cross-over dietary intervention human clinical trial was conducted with three pigmented rice varieties chosen from previous chemical and in vitro antioxidant and anti-inflammatory screening. Obese (n = 22, BMI > 30) sedentary participants consumed one cup of pigmented rice (Reiziq (brown), Purple (purple) and Yunlu29 (red)). Blood samples were collected prior consumption (baseline) and at set time points of 30 minutes, 1 hour, 2 hours and 4 hours post rice consumption. The collected blood samples were analysed for antioxidant and inflammatory biomarkers. Total antioxidant activity increased (p < 0.001) at the 1 hour time point by 40.3% post purple rice consumption. The red rice variety, Yunlu29 increased antioxidant activity at the 30 minute (p < 0.001) and 1 hour (p < 0.01) time point by 29.5% and 21.2% respectively. Lipid peroxidation biomarker, malondialdehyde (MDA), decreased (p < 0.05) at the 30 minute time point by 6.8% post purple rice consumption. At the 4 hour time point MDA levels was significantly reduced (p < 0.001) by the red rice variety Yunlu29, by 9.6%. Pro-inflammatory cytokine, interleukin-10 (IL-10), was significantly (p < 0.0001) reduced by 3.1% 30 minutes post purple rice consumption. In contrast, Yunlu29 (red) reduced interleukin-6 levels by 13.6% and 11.0% at the 30 minute and 1 hour time points respectively. Both the purple (p < 0.01) and red (p < 0.001) varieties significantly reduced interleukin-12p70 concentrations at 30 minutes by 8.7% and 10.3% respectively. Reiziq (brown) did not affect any of the biomarkers analysed in this study. The outcomes of this study highlight that polyphenols found in pigmented rice may play a key role in targeting specific therapeutic pathways in obesity-related oxidative stress and inflammation.

The pathogenesis of lifestyle diseases has been significantly correlated to high levels of oxidative stress and pro-inflammation. The antioxidant and anti-inflammatory properties of polyphenols in coloured rice varieties could have potential to neutralize oxidative stress and modulate inflammatory responses. A cross-over design, randomised, dietary intervention human clinical trial was conducted on a pre-screened healthy population (n = 24) investigating the antioxidant and anti-inflammatory potential of pigmented rice (purple, red and brown) varieties. Post baseline blood samples collection volunteers consumed a serve of cooked pigmented rice. Blood samples were collected at 30-minutes, 1, 2 and 4-hours post rice consumption. A one-week wash-out period between each supplementation bout (rice variety) was conducted. Blood and biochemical parameters were analysed on baseline blood samples. Antioxidant activity, malondialdehyde (MDA) and a pro-inflammatory cytokine panel were analysed on the blood samples collected. Post purple rice consumption, antioxidant activity increased (p < 0.0001) by 70.5% and maintained elevated for all time points. The red rice variety Yunlu29, significantly (p < 0.005) reduced MDA levels by 9.2% at the 30-minute time point. Purple rice demonstrated a significant (p < 0.05) decrease by 4.0% at the 30-minute time point only. Purple rice significantly decreased TNF-α levels at the 1-hour (p < 0.05) and 4-hour (p < 0.005) time points by 21.9% and 25.4% respectively. IL-6 concentrations were significantly reduced at 1 and 2-hour post Purple (p < 0.05; 11.7%) and Yunlu29 (red) (p < 0.01; 14.1%) consumption respectively. The brown rice variety did not affect any parameters tested. The outcomes of this study, highlight that polyphenols found in pigmented rice may play a key role in targeting specific oxidative stress and inflammatory therapeutic pathways. Pigmented rice varieties may serve as a potential functional food in reducing risk factors associated with lifestyle diseases.

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causative etiology of ‘Corona Virus Disease-2019' (COVID-19); formerly referred as ‘novel-Coronavirus-2019'. It was originated in Wuhan city, Hubei province, China in early December 2019. The World Health Organization (WHO) declared it as ‘Public Health Emergency of International Concern' due to their rapid transmission and causing public and health-care-related casualties worldwide. This review provides an updated overview of COVID-19 (SARS-CoV-2), in comparison with the etiologies of the same group viz. SARS and MERS and also its future perspectives for planning appropriate strategies for prevention, control and treatment modalities to avert similar catastrophe in near future.

Stroke is a significant source of morbidity and mortality within the United States. The current standard of care for treatment of acute ischemic stroke is intravenous recombinant tissue-type plasminogen activator (IV r-tPA). However, IV r-tPA is contraindicated within 3 months of a previous stroke due to concern for symptomatic intracerebral hemorrhage (sICH). We describe the case of a 77-year-old female who developed aphasia and right-sided quadrantanopsia and was found to have a calcified embolus in the M3 branch of her left middle cerebral artery. She was given IV r-tPA with subsequent symptom resolution and no MRI evidence of acute or subacute infarct. 4 days after index stroke, she had recurrence of her symptoms, receiving a second dose of IV r-tPA. She improved clinically. Non-contrast CT 24 hours afterwards showed minimal foci of intraparenchymal hemorrhage without midline shift or mass effect. She remained neurologically stable and improved significantly with inpatient rehabilitation.

Mitochondrial disorders have been an enigma for a long time due to the varied clinical presentations. Although a genetic confirmation will be mandatory most of the time, half the number of Leigh syndrome would be negative for genetic mutations. There are a growing number of mutations in clinical practice, which escape detection on routine clinical exome sequencing. Imaging would render help in pointing towards a mitochondrial disorder. There are a few case reports which brief about specific mitochondrial mutations and their specific imaging appearance. This article tries to provide a comprehensive review on the imaging-genomic correlation of mitochondrial disorders with an objective of performing a specific genetic testing to arrive at an accurate diagnosis.

Crohn's disease (CD) and ulcerative colitis are two main clinically defined forms of chronic inflammatory bowel disease (IBD). Chronic intestinal inflammation is inextricably linked to colitis-associated colon carcinogenesis (CAC). Patients with ulcerative colitis (UC) and Crohn's disease (CD) have an increased risk of colon cancer. Our understanding of IBD and IBD-associated colon carcinogenesis depends largely on rodent models. AOM-DSS-induced colitis-associated colon cancer in mice is the most widely used and accepted model that can recapitulate the human IBD-associated colon cancer. Here, we have provided detailed protocols of this mouse model of experimentally induced chronic intestinal inflammation-associated colon cancer. We will also discuss the protocols for the isolation and analysis of inflammatory immune cells from the colon.

Objectives Coronavirus disease is an infectious disease caused by a newly discovered coronavirus. This virus primarily spreads through droplets of saliva or discharge from the nose when an infected person coughs or sneezes. This virus was named after its shape, which takes the form of a crown with protrusions around it. The World Health Organization has recommended personal protective equipments (PPE) to doctors and health care workers attending COVID-19 patients. PPE generally includes masks, goggles, respirators, gloves, face shields, and isolation gowns. The principle aim of this study is to create awareness among dental students about the preventive measures taken by health care professionals while attending patients affected with COVID-19. Materials & Methods A questionnaire comprising 15 questions was created using an online Google forms website and was circulated among 100 dental students. The survey was conducted within a week in the months of April to May 2020. The results and observations were recorded in the form of pie charts. Results Ninety-three percent of the participants have stated that health care professionals must clean their hands often, cover their nose and mouth, and maintain safe distance from everyone in order to prevent the virus from affecting them. Sixty-three percent of the participants are familiar with the term PPE. Majority assume that health care professionals are given enough safety precautions while treating a patient with coronavirus. Conclusion Hence, to conclude, health care professionals play a vital role in improving access and quality health care for the population, and hence, they must be protected as well. Since dental students treat patients, they are vulnerable to infection as well, and must take proper safety measures.

Fumarate hydratase (FH), one of the members of TCA cycle, acts as a catalyte for the synthesis of malate from fumarate. FH has been proposed to play as a tumour suppressor leading to the pathogenicity of leiomyomas, renal cell carcinoma and paraganglioma. Mutations in the active site of FH lead to alteration in the protein structure. Similarly, binding of several chemical inhibitors to the active site also leads to the disruption of protein structural integrity thereby leading to protein dysfunction. Therefore, in order to address this mechanism leading to cancer, the binding efficiency of potential human FH inhibitor citrate to zebrafish fh has been extensively analysed in this study by molecular docking and simulation experiments followed by quantification of fumarate hydratase enzyme activity to validate and confirm the findings. Molecular docking revealed stronger interaction of zebrafish fh protein with inhibitor citrate when compared to natural substrate fumarate. Study on the dynamics of docked structures further confirmed that citrate was found to possess more binding affinity than fumarate. In vitro biochemical analysis also revealed concentration dependent potential inhibitory effect of citrate on zebrafish fh, thus confirming the findings of the in-silico experiments.Communicated by Ramaswamy H. Sarma.

Signaling through retinoic acid inducible gene I (RIG-I) like receptors (RLRs) is tightly regulated, with activation occurring upon sensing of viral nucleic acids, and suppression mediated by negative regulators. Under homeostatic conditions aberrant activation of melanoma differentiation-associated protein-5 (MDA5) is prevented through editing of endogenous dsRNA by RNA editing enzyme Adenosine Deaminase Acting on RNA (ADAR1). In addition, ADAR1 is postulated to play pro-viral and antiviral roles during viral infections that are dependent or independent of RNA editing activity. Here, we investigated the importance of ADAR1 isoforms in modulating influenza A virus (IAV) replication and revealed the opposing roles for ADAR1 isoforms, with the nuclear p110 isoform restricting versus the cytoplasmic p150 isoform promoting IAV replication. Importantly, we demonstrate that p150 is critical for preventing sustained RIG-I signaling, as p150 deficient cells showed increased IFN-β expression and apoptosis during IAV infection, independent of RNA editing activity. Taken together, the p150 isoform of ADAR1 is important for preventing sustained RIG-I induced IFN-β expression and apoptosis during viral infection., Author summary Viruses as intracellular pathogens need to precisely block or usurp certain host proteins to create a hospitable environment for viral replication. In this study, we investigated the significance of host protein ADAR1 and different isoforms of ADAR1 in influenza virus replication. Through gene deletion of specific ADAR1 isoforms, our study reveals opposing roles for the two isoforms of ADAR1. Influenza virus replication was increased in cells lacking the p110 isoform of ADAR1, indicating that p110 hinders influenza virus replication. In contrast, cells lacking the p150 isoform of ADAR1 showed decreased influenza virus replication, indicating that p150 promotes influenza virus replication. In response to viral infection, host cells mount antiviral defenses to contain viral spread and these antiviral defenses when left unchecked can cause excessive inflammation and tissue damage. As such, antiviral defense pathways are tightly controlled by positive and negative regulators to prevent aberrant activation or to shut-down inflammatory responses in a timely manner. In this study, we have identified that p150 deficient cells exhibit uncontrolled activation of antiviral pathways and increased cell death during influenza virus infection, creating an inhospitable environment in the cell for viral replication. In summary, our studies reveal that the p150 isoform of ADAR1 promotes influenza virus replication by regulating cellular antiviral defense pathways.

Tracheal tumor is a rare entity. Tracheal tumor may be a primary tracheal tumor or secondary to invasion from a mediastinal tumor (or a lymph node). These tumors are prone to cause critical airway obstruction which may require urgent care. Tuberculosis is one of the common differential diagnoses of mediastinal lymphadenopathy in TB endemic countries, though isolated tuberculous mediastinal lymphadenopathy without a lung involvement is rare. We report an extremely rare case of isolated paratracheal lymphadenitis due to tuberculosis, eroding the trachea and presented a lower tracheal tumor, which recurred again after complete debulking. Finally, the disease required a ‘Y’ stent placement, to stabilize the airway following the second recanalization. We discuss the incidence, differential diagnosis, and the bronchoscopic, interventional aspects of this entity.

RAD51-associated protein 1 (RAD51AP1) plays an integral role in homologous recombination by activating RAD51 recombinase. Homologous recombination is essential for preserving genome integrity and RAD51AP1 is critical for D-loop formation, a key step in homologous recombination. Although RAD51AP1 is involved in maintaining genomic stability, recent studies have shown that RAD51AP1 expression is significantly upregulated in human cancers. However, the functional role of RAD51AP1 in tumor growth and the underlying molecular mechanism(s) by which RAD51AP1 regulates tumorigenesis have not been fully understood. Here, we use Rad51ap1-knockout mice in genetically engineered mouse models of breast cancer to unravel the role of RAD51AP1 in tumor growth and metastasis. RAD51AP1 gene transcript was increased in both luminal estrogen receptor–positive breast cancer and basal triple-negative breast cancer, which is associated with poor prognosis. Conversely, knockdown of RAD51AP1 (RADP51AP1 KD) in breast cancer cell lines reduced tumor growth. Rad51ap1-deficient mice were protected from oncogene-driven spontaneous mouse mammary tumor growth and associated lung metastasis. In vivo, limiting dilution studies provided evidence that Rad51ap1 plays a critical role in breast cancer stem cell (BCSC) self-renewal. RAD51AP1 KD improved chemotherapy and radiotherapy response by inhibiting BCSC self-renewal and associated pluripotency. Overall, our study provides genetic and biochemical evidences that RAD51AP1 is critical for tumor growth and metastasis by increasing BCSC self-renewal and may serve as a novel target for chemotherapy- and radiotherapy-resistant breast cancer. Significance: This study provides in vivo evidence that RAD51AP1 plays a critical role in breast cancer growth and metastasis by regulating breast cancer stem cell self-renewal.

Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca2+ channels, Ca2+ permeable AMPA receptors, and purinergic P2X7 receptors respectively, effectively limits secondary consequences of injury in in vitro and in vivo models of CNS injury. Here, we investigated the efficacy of these inhibitors in a clinically relevant model of SCI. Fischer (F344) rats were subjected to a moderate (150 kD) contusive SCI at thoracic level T10 and assessed at 2 weeks or 10 weeks post-injury. Lom was delivered orally twice daily and YM872 and oxATP were delivered via osmotic mini-pump implanted at the time of SCI until 2 weeks following injury. Open field locomotion analysis revealed that treatment with the three inhibitors in combination improved the rate of functional recovery of the hind limb (compared to controls) as early as 1-day post-injury, with beneficial effects persisting to 14 days post-injury, while all three inhibitors were present. At 2 weeks following combinatorial treatment, the functional improvement was associated with significantly decreased cyst size, increased immunoreactivity of β-III tubulin+ve axons, myelin basic protein, and reduced lipid peroxidation by-products, and increased CC1+ve oligodendrocytes and NG2+ve/PDGFα+ve oligodendrocyte progenitor cell densities, compared to vehicle-treated SCI animals. The combination of Lom, oxATP, and YM872 shows preclinical promise for control of secondary degeneration following SCI, and further investigation of long-term sustained treatment is warranted.

Oxidative stress and inflammation are known to be linked to the development of chronic inflammatory conditions, such as type 2 diabetes and cardiovascular disease. Dietary polyphenols have been demonstrated to contain potent bioactivity against specific inflammatory pathways. Rice bran (RB), a by-product generated during the rice milling process, is normally used in animal feed or discarded due to its rancidity. However, RB is known to be abundant in bioactive polyphenols including phenolic acids. This study investigates the antioxidant and anti-inflammatory effects of RB phenolic extracts (25, 50, 100, and 250 &micro, g/mL) on RAW264.7 mouse macrophage cells stimulated with hydrogen peroxide and lipopolysaccharide. Biomarkers of oxidative stress and inflammation such as malondialdehyde (MDA), intracellular reactive oxygen species, nitric oxide and pro-inflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), interleukin-10 (IL-10), tumor necrosis factor-&alpha, (TNF-&alpha, ), interleukin-12, p70 (IL-12p70), and interferon-&gamma, (IFN-&gamma, ) were measured in vitro. Treatment with RB extracts significantly decreased the production of MDA, intracellular reactive oxygen species, nitric oxide and pro-inflammatory cytokines (IL-6, IL-12p70, and IFN-&gamma, ) when compared to the control. It is proposed that RB phenolic extracts, via their metal chelating properties and free radical scavenging activity, target pathways of oxidative stress and inflammation resulting in the alleviation of vascular inflammatory mediators.

Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas.

Introduction: Hypercalcaemia can be caused by many disorders. Primary hyperparathyroidism is the leading cause with parathyroidectomy being the definitive management. Familial hypocalciuric hypercalcaemia is a rarer cause in which resection of the parathyroid tissue does not result in normalized serum calcium. Case presentation: We report the unusual case of a 53-year-old lady who presented with hypercalcaemia and elevated parathyroid hormone with a presumed diagnosis of primary hyperparathyroidism. She remained hypercalcaemic after parathyroidectomy and was later diagnosed with familial hypocalciuric hypercalcaemia. During the first operation, a lymph node was also removed, and the histopathology report suggested a metastasis of follicular variant papillary thyroid carcinoma (FVPTC). After multi-disciplinary team (MDT) discussion, the patient underwent a second exploration where total thyroidectomy and removal of the other parathyroid glands were performed. Hypercalcaemia completely resolved on surgical resection of the thyroid and parathyroid tissue, however histopathology revealed normal parathyroid glands and florid Hashimoto's thyroiditis. The initial diagnosis of FVPTC in the lymph node was revisited and the final histopathology report suggested an accessory thyroid nodule with florid Hashimoto's thyroiditis mimicking a lymph node. Conclusion: Our case demonstrates the diagnostic dilemma in hypercalcaemia that may lead a patient to undergo unnecessary invasive procedures; the misdiagnosis of FVPTC after the first operation resulted in a second more extensive procedure. Patients with no clear surgical target and urine CCCR in the gray/non-diagnostic area should be routinely offered genetic testing despite negative family history.

Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11–13, 28–42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs, while it progressively increased in SGCs. Consequently, GCs’ input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady-state inhibition between GCs and SGCs which could confound their use in classifying the cell types.

Traumatic brain injury often leads to progressive alterations at the molecular to circuit levels resulting in epilepsy and memory impairments. Ex vivo and in vitro models have provided a powerful platform for investigating the multimodal alteration after trauma. Recent ex vivo analyses using voltage sensitive dye imaging, optogenetics, and glutamate uncaging have revealed circuit abnormalities following in vivo brain injury. In vitro injury models have enabled examination of early and progressive changes in activity while development of three-dimensional organoids derived from human induced pluripotent stem cells have opened novel avenues for injury research. Here, we highlight recent advances in ex vivo and in vitro systems, focusing on their potential for advancing mechanistic understandings, possible limitations, and implications for therapeutics.

Oxidative stress is known to modulate insulin secretion and initiate gene alterations resulting in impairment of &beta, cell function and type 2 diabetes mellitus (T2DM). Rice bran (RB) phenolic extracts contain bioactive properties that may target metabolic pathways associated with the pathogenesis of T2DM. This study aimed to examine the effect of stabilized RB phenolic extracts on the expression of genes associated with &beta, cell function such as glucose transporter 2 (Glut2), pancreatic and duodenal homeobox 1 (Pdx1), sirtuin 1 (Sirt1), mitochondrial transcription factor A (Tfam), and insulin 1 (Ins1) in addition to evaluating its impact on glucose-stimulated insulin secretion. It was observed that treatment with different concentrations of RB phenolic extracts (25-250 &micro, g/mL) significantly increased the expression of Glut2, Pdx1, Sirt1, Tfam, and Ins1 genes and glucose-stimulated insulin secretion under both normal and high glucose conditions. RB phenolic extracts favourably modulated the expression of genes involved in &beta, cell dysfunction and insulin secretion via several mechanisms such as synergistic action of polyphenols targeting signalling molecules, decreasing free radical damage by its antioxidant activity, and stimulation of effectors or survival factors of insulin secretion.

Influenza viruses cause upper respiratory tract infections in humans. In healthy adults, seasonal influenza virus infections result in mild disease. Occasionally, influenza viruses endemic in domestic birds can cause severe and fatal disease even in healthy individuals. In avian influenza virus-infected patients, the host immune system is activated in an uncontrolled manner and is unable to control infection in a timely fashion. In this study, we investigated why the immune system fails to effectively control a modified form of avian influenza virus. Our studies show that T cell functions important for clearing virally infected cells are impaired by higher negative regulatory signals during modified avian influenza virus infection. In addition, memory T cell numbers were decreased in modified avian influenza virus-infected mice. Our studies provide a possible mechanism for the severe and prolonged disease associated with avian influenza virus infections in humans., Seasonal influenza virus infections cause mild illness in healthy adults, as timely viral clearance is mediated by the functions of cytotoxic T cells. However, avian H5N1 influenza virus infections can result in prolonged and fatal illness across all age groups, which has been attributed to the overt and uncontrolled activation of host immune responses. Here, we investigate how excessive innate immune responses to H5N1 impair subsequent adaptive T cell responses in the lungs. Using recombinant H1N1 and H5N1 strains sharing 6 internal genes, we demonstrate that H5N1 (2:6) infection in mice causes higher stimulation and increased migration of lung dendritic cells to the draining lymph nodes, resulting in greater numbers of virus-specific T cells in the lungs. Despite robust T cell responses in the lungs, H5N1 (2:6)-infected mice showed inefficient and delayed viral clearance compared with H1N1-infected mice. In addition, we observed higher levels of inhibitory signals, including increased PD-1 and interleukin-10 (IL-10) expression by cytotoxic T cells in H5N1 (2:6)-infected mice, suggesting that delayed viral clearance of H5N1 (2:6) was due to the suppression of T cell functions in vivo. Importantly, H5N1 (2:6)-infected mice displayed decreased numbers of tissue-resident memory T cells compared with H1N1-infected mice; however, despite the decreased number of tissue-resident memory T cells, H5N1 (2:6) was protected against a heterologous challenge from H3N2 virus (X31). Taken together, our study provides mechanistic insight for the prolonged viral replication and protracted illness observed in H5N1-infected patients. IMPORTANCE Influenza viruses cause upper respiratory tract infections in humans. In healthy adults, seasonal influenza virus infections result in mild disease. Occasionally, influenza viruses endemic in domestic birds can cause severe and fatal disease even in healthy individuals. In avian influenza virus-infected patients, the host immune system is activated in an uncontrolled manner and is unable to control infection in a timely fashion. In this study, we investigated why the immune system fails to effectively control a modified form of avian influenza virus. Our studies show that T cell functions important for clearing virally infected cells are impaired by higher negative regulatory signals during modified avian influenza virus infection. In addition, memory T cell numbers were decreased in modified avian influenza virus-infected mice. Our studies provide a possible mechanism for the severe and prolonged disease associated with avian influenza virus infections in humans.

Objective Wrist deformity in older people is common following treatment for a wrist fracture, particularly after non-surgical treatment. A cohort of older wrist fracture patients were surveyed by telephone regarding perceived deformity, bother with deformity and patient-reported wrist function. The objectives were to: (1) determine whether older patients with wrist fractures perceived a deformity of their wrist and if they were bothered by it; (2) test if there were associations between deformity and treatment-type and between deformity and function; (3) test for associations between bother and treatment-type and between bother and function; (4) measure the test–retest reliability of the ‘bother’ question. Results Of 98 eligible patients who were invited to participate, 41 responded. Out of 41, 14 (34%) believed they had a deformity and 4 (10%) reported that they were bothered by the appearance of their wrist. Deformity was associated with non-surgical treatment (RR = 3.85, p = 0.006) but was not significantly associated with functional outcomes (p = 0.15). All those who were bothered belonged to the non-surgical treatment group. Bother was significantly associated with poorer functional outcomes (p = 0.006) and this association was clinically significant (MD = 35 points). The deformity and bother questions were found to have excellent test–retest reliability; κ = 1.00 and κ = 0.92, respectively.

Digital learning has gained a lot of attention over the recent years and is increasingly being utilised as a substitute for both distance education and face-to face learning activities. This chapter initially defines and briefly discusses the advantages and disadvantages of digital learning. With the advancement in technology, there are various digital tools that are now available to enhance the effectiveness of digital learning experience, and some of the major innovative digital tools are detailed in the chapter.

Global obesity rates are of epidemic proportion. With limited treatments available there is a large demand for therapeutic alternatives. Polyphenols derived from coloured rice varieties may serve as a potential functional food alternative in combating obesity and obesity-related diseases. The antioxidant and anti-inflammatory properties of polyphenols found in coloured rice varieties could have the ability to neutralize oxidative stress and modulate inflammatory responses in obese populations. This review discusses polyphenols derived from rice, the oxidative stress and inflammatory pathways involved in obesity pathogenesis, bioavailability of polyphenols and the therapeutic potential of polyphenols on transcriptional and molecular pathways related to obesity and obesity-related diseases.

Phenolic composition and relative antioxidant activity were investigated in six varieties of sorghum including pigmented and non-pigmented pericarp varieties. Whole grain sorghum extracts were subjected to acidified acetone extraction and were analysed using UHPLC with an attached online ABTS system and Q-TOF LC/MS. Results showed that the black pericarp variety Shawaya short black 1 and the brown pericarp variety IS11316 had the highest total phenolic content (TPC) and total proanthocyanidin content (TPAC), consequently resulting in overall high antioxidant activity. The phenolic compounds that had the highest antioxidant activity in Shawaya and IS11316 were catechin, 1-O-cafferolglycerol-O-glucoside, taxifolin and pentahydroxyflavanone-(3->4)-catechin-7-O-glucoside. Furthermore, comparison of the phenolic profiles has shown that the varieties with higher antioxidant activity generally had higher quantities and more diverse range of polyphenols. Thus, this study indicates that there is no independent compound in sorghum that results in its high antioxidant activity but rather it is the cumulative effect of various phenolic compounds.

Oculocutaneous albinism type 4 (OCA4) is a form of inborn errors of metabolism leading to absence of pigmentation or hypopigmentation in the skin, hair and eyes. A membrane associated transporter protein (MATP) coded by Solute carrier family 45, member 2 (SLC45A2) is found to be directly linked with the disease phenotype. In this study, we categorized deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) for this gene from the available Ensembl data. We predicted the native protein model for MATP using threading methodology and subsequently incorporated the amino acid changes corresponding to the deleterious nsSNPs to develop mutant models. Subsequently, stability and structural differences of the predicted models were analyzed. We identified 3 nsSNPs corresponding to G44R, G110R and A486V amino acid changes, to potentially damage the transmembrane helices of the protein and these nsSNPs have also been reported in OCA4 patients.