Mental health problems raise the odds of cognitive impairment in COVID-19 survivors.

Background: COVID-19 survivors around the globe are suffering from mental health issues. While mental health problems can be an early warning sign of dementia, they may also increase the chances of developing the disease. In this study, we examined the mental health of COVID-19 survivors and mapped its associations with cognitive and demographic variables. Method: COVID-19 survivors listed in the databases of three tertiary care hospitals in Kolkata were contacted sequentially. 376 willing patients were interviewed over the telephone. 99 COVID-19 patients and 31 matched controls participated in the in-person interviews that were arranged for a more detailed investigation. The participants were administered standardized tests that are widely used for the assessment of cognitive functioning and mental health status. Result: 64.89% of COVID-19 survivors reported a deterioration in physical functioning. 44.95% reported a decline in mental health, whereas 41.49% reported a drop in cognitive performance. Detailed investigations revealed that they had an increased risk of having depression, anxiety, and poor sleep quality by 91%, 68%, and 140%, respectively. 6.1% of the patients had mild cognitive impairment, and 4% had dementia. COVID-19 patients who had depression and anxiety were 8.6 and 19.4 times more likely to have cognitive decline, respectively. Compared to the matched controls, COVID-19 patients had greater depression (p<.001), anxiety (p<.001), stress (p =.003), and insomnia (p <.001). They also scored significantly lower on Addenbrooke's Cognitive Examination-III (p =.009) and Picture Naming Test (p =.005) and took significantly longer to complete Trail Making Test-A (p =.002). Conclusion: COVID-19 survivors in this study had major mental health issues even one year after contracting the virus. They had significant cognitive deficits that might progress into dementia. Strict monitoring and systematic treatment plans should be implemented as soon as possible.

Blends of Carboxymethyl Cellulose and Cottonseed Protein as Biodegradable Films.

With the increasing awareness of plastic pollution in the environment and the accumulation of microplastics in water, a significant amount of research and development is ongoing to replace the synthetic plastics in packaging and coatings. In this work, we explored the blends of carboxymethyl cellulose (CMC) and washed cottonseed meal (CSM, consisting mostly of cottonseed protein) as agro-based, biodegradable, and sustainable alternatives to plastics. Glycerol was found to be a suitable plasticizer for these blends. The blends of CMC/CSM were produced as single-layer films from 50 to 90 µm in thickness, consisting of different proportions of the components and plasticizer. The evaluated properties included opacity, water vapor permeability, mechanical properties, thermogravimetric analysis, moisture sorption analysis, and water swelling test. Higher percentages of CSM in the blend resulted in higher opacity and lower water vapor permeation rates. The mechanical strength waned with lower levels of CMC. Possible applications for these blends include their use as water-soluble food packaging and coatings and as dissolvable bags and pouches for detergents and agrochemicals.

On the Unique Morphology and Elastic Properties of Multi-Jet Electrospun Cashew Gum-Based Fiber Mats.

This study investigates the unique morphology and mechanical properties of multi-jet electrospun cashew gum (CG) when combined with high-molecular-weight polyethylene oxide (PEO) and glycerol. Cashew gum (CG) is a low-cost, non-toxic heteropolysaccharide derived from Anacardium occidentale trees. Initially, the electrospinnability of aqueous solutions of cashew gum alone or in combination with PEO was evaluated. It was found that cashew gum alone was not suitable for electrospinning; thus, adding a small quantity of PEO was needed to create the necessary molecular entanglements for fiber formation. By using a single emitter with a CG:PEO ratio of 85:15, straight and smooth fibers with some defects were obtained. However, additional purification of the cashew gum solution was needed to produce more stable and defect-free straight and smooth fibers. Additionally, the inclusion of glycerol as a plasticizer was required to overcome material fragility. Interestingly, when the optimized formulation was electrospun using multiple simultaneous emitters, thicker aligned fiber bundles were achieved. Furthermore, the resulting oriented fiber mats exhibited unexpectedly high elongation at break under ambient conditions. These findings underscore the potential of this bio-polysaccharide-based formulation for non-direct water contact applications that demand elastic properties.

NMR Analyses and Statistical Modeling of Biobased Polymer Microstructures-A Selected Review.

NMR analysis combined with statistical modeling offers a useful approach to investigate the microstructures of polymers. This article provides a selective review of the developments in both the NMR analysis of biobased polymers and the statistical models that can be used to characterize these materials. The information obtained from NMR and statistical models can provide insights into the microstructure and stereochemistry of appropriate biobased polymers and establish a systematic approach to their analysis. In suitable cases, the analysis can help optimize the synthetic procedures and facilitate the development of new or modified polymeric materials for various applications. Examples are given of the studies of poly(hydroxyalkanoates), poly(lactic acid), and selected polysaccharides, e.g., alginate, pectin, and chitosan. This article may serve as both a reference and a guide for future workers interested in the NMR sequence analysis of biobased materials.

An Effort to Identify Genetic Determinants in Siblings With Wilson Disease Manifesting Striking Clinical Heterogeneity: An Exome Profiling Study of Two Indian Families.

BACKGROUND: Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism caused due to mutations in the copper transporter ATP7B. There is often a striking variability of clinical manifestations among patients with ATP7B mutations, including in siblings. This phenomenon may be caused by individual differences in copper accumulation in hepatocytes and intolerance to copper toxicity as governed by genetic variations in copper metabolism genes acting as modifier loci to the disease. OBJECTIVE: To elucidate the genetic basis of striking clinical heterogeneity among two siblings of two families with WD. METHODS: The disease diagnosis and subsequent clinical examinations were performed by expert clinicians. The younger siblings in both families presented with early neurological manifestations at a younger age than their older siblings. Interestingly, only the younger siblings were reported to have had hepatic manifestations. Exome sequencing of all the four individuals was performed to understand their heterogeneous phenotypic outcomes. RESULTS: Genetic screening revealed no difference in the ATP7B variant spectrum between the siblings of each family. However, the siblings of both the families were found to harbor mutually exclusive pathogenic variants in suspected modifier genes implicated in copper metabolism and/or other neurological and hepatic disorders having overlapping symptoms with WD, viz., CFTR, PPARG, ABCB11, ATP7A, CYP2D6, mTOR, TOR1A, and CP, which can potentially explain their differential clinical phenotypes. CONCLUSION: Clinical heterogeneity between siblings with WD with the same ATP7B mutation profile may be attributed to the presence of different pathogenic variants in potential modifier genes.

Illiterate Addenbrooke's Cognitive Examination-III in Three Indian Languages: An Adaptation and Validation Study.

BACKGROUND: Literacy is an important factor that predicts cognitive performance. Existing cognitive screening tools are validated only in educated populations and are not appropriate for older adults with little or no education leading to poor performance on these tests and eventually leading to misdiagnosis. This challenge for clinicians necessitates a screening tool suitable for illiterate or low-literate older individuals. OBJECTIVES: The objective was to adapt and validate Addenbrooke's Cognitive Examination-III (ACE-III) for screening general cognitive functions in illiterate and low-literate older populations in the Indian context in three languages. METHOD: The Indian illiterate ACE-III was systematically adapted by modifying the original items of the Indian literate ACE-III to assess the cognitive functions of illiterates and low-literates with the consensus of an expert panel of professionals working in the area of dementia and related disorders. A total of 180 illiterate or low-literate participants (84 healthy-controls, 50 with dementia, and 46 with mild cognitive impairment [MCI]) were recruited from three different centers speaking Bengali, Hindi, and Kannada to validate the adapted version. RESULTS: The optimal cut-off score for illiterate ACE-III to distinguish controls from dementia in all 3 languages was 75. The optimal cut-off scores in distinguishing between controls and MCI ranged from 79 to 82, with a sensitivity ranging from 93% to 99% and a specificity ranging from 72% to 99%. CONCLUSION: The test is found to have good psychometric properties and is a reliable cognitive screening tool for identifying dementia and MCI in older adults with low educational backgrounds in the Indian context.

Analysis of Semiology, Lesion Topography and Treatment Outcomes: A Prospective Study on Post Thalamic Stroke Holmes Tremor.

OBJECTIVE: Holmes tremor (HT) comprises rest, postural and intention tremor subtypes, usually involving both proximal and distal musculature. Perturbations of nigro-striatal pathways might be fundamental in the pathogenesis of HT along with cerebello-thalamic connections. METHODS: Nine patients with an HT phenotype secondary to thalamic stroke were included. Epidemiological and clinical records were obtained. Structural and functional brain imaging were performed with magnetic resonance imaging (MRI) or computed tomography (CT) and positron emission tomography (PET), respectively. Levodopa was administered in sequentially increasing dosage, with various other drugs in case of inadequate response. Longitudinal follow-up was performed for at least three months. The essential tremor rating assessment scale (TETRAS) was used for assessment. RESULTS: The mean latency from stroke to tremor onset was 50.4 ± 30.60 days (range 21-90 days). Dystonia was the most frequently associated hyperkinetic movement (88.8%). Tremor was bilateral in 22.2% of participants. Clinical response was judged based on a reduction in the TETRAS score by a prefixed value (≥ 30%), pertaining to which 55.5% (n = 5) of subjects were classified as responders and the rest as non-responders. The responders showed improvement with significantly lower doses of levodopa than the remaining nonresponders (240 ± 54.7 mg vs. 400 ± 40.8 mg; p = 0.012). CONCLUSION: Although levodopa is useful in HT, augmenting the dosage of levodopa beyond a certain point might not benefit patients clinically. Topography of vascular lesions within the thalamus might additionally influence the phenomenology of HT.

The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

BACKGROUND: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused. OBJECTIVE: The aim was to identify genetic risk factors for PD in a South Asian population. METHODS: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO. RESULTS: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease. CONCLUSIONS: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Arg4810Lys mutation in RNF213 among Eastern Indian non-MMD ischemic stroke patients: a genotype-phenotype correlation.

INTRODUCTION: RNF213 mutations have been reported mostly in moyamoya disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset ischemic stroke is still not well explored. AIMS AND OBJECTIVES: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD ischemic stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analyzed for this variant using PCR-RFLP and confirmed using Sanger sequencing method. RESULT AND CONCLUSION: We have identified Arg4810Lys variant among eleven young-onset familial ischemic stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age at onset (P = 0.002), and history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial ischemic stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.

Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment Among Eastern Indians.

Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes, BDNF and (b) dysregulation in expression level of CLOCK, BMAL1, and BDNF that may be associated with PSCI. BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C), and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its 'C' allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the 'CC' genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression for CLOCK and BDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike Pro-BDNF, plasma-level mBDNF was also lower in them. Our results suggest the genetic variants in CLOCK, CRY2, and BDNF as risk factors for PSCI among eastern Indians. At the same time, a lowering expression of CLOCK and BDNF genes in PSCI patients than controls describes their transcriptional dysregulation as underlying mechanism for post-stroke cognitive decline.

The scope of using pragmatic language tests for early detection of dementia: A systematic review of investigations using figurative language.

INTRODUCTION: Dementia cases are expected to rise to 81.1 million in 2040. Efforts are underway to develop diagnostic methods to facilitate early detection of the disease. Herein we review research findings focusing on pragmatic dysfunction in patients with dementia and evaluate the usefulness of assessing dementia and its progress with a battery of tests assessing figurative language skills. METHODS: A total of 74,778 article titles were identified from EMBASE, PubMed, and Google Scholar databases. After systematic screening, 51 journal articles were selected for the final review. RESULT: The review suggests that impaired figurative language might be a marker for early cognitive decline. Different forms of figurative language may be impaired at different stages of the disease and in different types of dementia involving different neuropathologies. CONCLUSION: The use of pragmatic tests in combination with the existing diagnostic protocols might increase the probability of early diagnosis. HIGHLIGHTS Pragmatic impairment could be a marker of early cognitive impairment. Figurative language-an important pragmatic aspect-is disrupted in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Figurative language impairment might precede literal language impairment. Pragmatic tests could be more sensitive than standard neuropsychological tests. Inclusion of pragmatic tests in diagnostic guidelines might bolster early detection.

Sample sizes required to estimate the protective efficacy of a vaccine when there is an unequal allocation of individuals across the vaccine and placebo groups.

The effectiveness of a vaccine is measured by means of protective vaccine efficacy, defined by VE=1-ARVARU, where ARV and ARU are, respectively, the disease attack rates in the vaccinated and the unvaccinated population. For each of the cohoret and case-control designs, methods have been presented in the literature for calculating the required sample size when the desired width of the confidence interval and the probability of coverage are pre-specified, where an equal number of individuals were assumed to be allocated to the vaccine and placebo group. In this article, we present a method for calculating the required sample size with a specified degree of precision when there is an unequal allocation of individuals across the two groups. The sample size required to achieve a desired power for the relevant level α test has also been explored, keeping the unequal allocation proportion in mind. The fraction of individuals allocated to the placebo group (ρ) can be so chosen that the total sample size or the expected number of people developing the disease or some other criteria of interest is minimized.

Gastrointestinal, Respiratory, and Olfactory Neurotropism of Sars-Cov2 as a Possible Trigger of Parkinson's Disease: Is a Multi-Hit Multi-Step Process on the Cards.

Since the first emergence of COVID-19 on the global stage, there has been a wealth of evidence to suggest that SARS-Cov2 is not merely a pulmonary pathogen. This virus is unique in its ability to disrupt cellular pathways related to protein homeostasis, mitochondrial function, stress response, and aging. Such effects raise concerns about the long-term fate of survivors of COVID-19 infection, particularly regarding neurodegenerative diseases. The concept of interaction between environmental factors and alpha-synuclein formation in the olfactory bulb and vagal autonomic terminals with subsequent caudo-cranial migration has received much attention in the context of PD pathogenesis. Anosmia and gastrointestinal symptoms are two well-known symptoms of COVID-19, with evidence of an olfactory bulb and vagal infiltration by SARS-CoV2. This raises the possibility of the spread of the viral particles to the brain along multiple cranial nerve routes. Neurotropism, coupled with the ability of the SARS-Cov2 virion to induce abnormal protein folding and stress responses in the central nervous system, in presence of an inflammatory milieu, reinforced by hypoxia, coagulopathy, and endothelial dysfunction, reverberates the intriguing possibility of activation of a neurodegenerative cascade leading to the development of pathological alpha-synuclein aggregates and thus, triggering the development of PD in survivors of COVID19. This review attempts to summarize and critically appraise existing evidence from basic science research and clinical reports of links between COVID-19 and PD and explores the prospect of a multi-hit pathophysiological process, induced by SARS-Cov2 infection, ultimately converging on perturbed cellular protein homeostasis, which although is intriguing, presently lacks robust evidence for confirmation.

An Indian Young-onset Dementia With Parkinsonism With Double Heterozygous Mutations in ABCA7 and PRKN Identified Through Whole-exome Sequencing.

Alzheimer disease and Parkinson disease dementia are the 2 most common neurodegenerative diseases have substantial overlap in pathologic, genetic, and clinical manifestation and complex in nature. Here, for the first time, we report an Indian female young patient who presented with clinical manifestation of both Alzheimer disease and Parkinsonism, including dystonia with rapid disease progression. We identified a heterozygous mutation in the ATP-binding cassette transporter A7 gene and double heterozygous mutation in PRKN by whole-exome sequencing. This case is an example of complex etiology of neurodegenerative disorders and highlights the importance of genetic tests, including whole-exome sequencing in complex diseases.

Bilayer Films of Poly(lactic acid) and Cottonseed Protein for Packaging Applications.

Poly(lactic acid) (PLA) is a common biobased film-former made from renewable biomass, such as polysaccharides from sugarcane, corn, or cassava. It has good physical properties but is relatively expensive when compared to the plastics used for food packaging. In this work, bilayer films were designed, incorporating a PLA layer and a layer of washed cottonseed meal (CSM), an inexpensive agro-based raw material from cotton manufacturing, where the main component is cottonseed protein. These bilayer films were made through the solvent casting method. The combined thickness of the PLA/CSM bilayer film was between 47 and 83 µm. The thickness of the PLA layer in this film was 10%, 30%, or 50% of the total bilayer film's thickness. Mechanical properties of the films, opacity, water vapor permeation, and thermal properties were evaluated. Since PLA and CSM are both agro-based, sustainable, and biodegradable, the bilayer film may be used as an eco-friendlier food packaging material, which helps reduce the environmental problems of plastic waste and microplastics. Moreover, the utilization of cottonseed meal may add value to this cotton byproduct and provide a potential economic benefit to cotton farmers.