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A 34-year-old woman presented with insidious onset and gradually progressive cerebellar ataxia over 10 years, with generalised convulsions. On examination, there were myoclonic jerks, choreiform movements and cerebellar syndrome. Her family history suggested an autosomal dominant inheritance with anticipation. Genetic analysis for trinucleotide repeat disorders led to a diagnosis of dentatorubral-pallidoluysian atrophy (60 CAG repeats in the atrophin-1 gene). This rare spinocerebellar ataxia should be considered in the differential diagnosis of inherited ataxia when combined with seizures and chorea. Other features suggesting a repeat expansion disorder are variable phenotypes within the same family and possible anticipation.
ABSTRACT
Cardiovascular diseases (CVDs) are one of the major reasons for deaths globally. The renin-angiotensin-aldosterone system (RAAS) regulates body hypertension and fluid balance which causes CVD. Angiotensin-converting enzyme I (ACE I) is the central Zn-metallopeptidase component of the RAAS playing a crucial role in maintaining homeostasis of the cardiovascular system. The available drugs to treat CVD have many side effects, and thus, there is a need to explore phytocompounds and peptides to be utilized as alternative therapies. Soybean is a unique legume cum oilseed crop with an enriched source of proteins. Soybean extracts serve as a primary ingredient in many drug formulations against diabetes, obesity, and spinal cord-related disorders. Soy proteins and their products act against ACE I which may provide a new scope for the identification of potential scaffolds that can help in the design of safer and natural cardiovascular therapies. In this study, the molecular basis for selective inhibition of 34 soy phytomolecules (especially of beta-sitosterol, soyasaponin I, soyasaponin II, soyasaponin II methyl ester, dehydrosoyasaponin I, and phytic acid) was evaluated using in silico molecular docking approaches and dynamic simulations. Our results indicate that amongst the compounds, beta-sitosterol exhibited a potential inhibitory action against ACE I.
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Background: In spite of advancements in treatment options for MCA infarct, there is a definite role of decompressive hemicraniectomy. When compared with best medical management, it decreases mortality and improves functional outcome. But does surgery improve quality of life in terms of independence, cognition or it merely leads to increased survival? Objective: Outcome of 43 consecutive patients of MMCAI who underwent DHC was studied. Materials and Methods: Functional outcome was evaluated based on mRS and GOS in addition to survival advantage. The patient's proficiency in performing ADL was evaluated. MMSE and MOCA were performed to evaluate the neuropsychological outcome. Results: In-hospital mortality was 18.6%, and by 3 months, 67.5% of patients survived. During follow-up, nearly 60% of patients showed improvement in functional outcome when evaluated based on mRS and GOS. No patient could reach to the level of independent existence. Only eight patients could perform MMSE and five had good score (>24). All were young and had a right-sided lesion. None of the patients could perform well in MOCA. Conclusion: DHC improves survival and functional outcome. Cognition remains poor in the majority of the patients. These patients, though survive the stroke, remain dependent on care givers.
Subject(s)
Decompressive Craniectomy , Stroke , Humans , Infarction, Middle Cerebral Artery/surgery , Treatment Outcome , Quality of Life , Stroke/surgery , Retrospective StudiesABSTRACT
Plant growth-promoting endophytic microbes have drawn the attention of researchers owing to their ability to confer fitness benefits in many plant species. Here, we report agriculturally beneficial traits of rice-leaf-adapted endophytic Microbacterium testaceum. Our polyphasic taxonomic investigations revealed its identity as M. testaceum. The bacterium displayed typical endophytism in rice leaves, indicated by the green fluorescence of GFP-tagged M. testaceum in confocal laser scanning microscopy. Furthermore, the bacterium showed mineral solubilization and production of IAA, ammonia, and hydrolytic enzymes. Tobacco leaf infiltration assay confirmed its non-pathogenic nature on plants. The bacterium showed antifungal activity on Magnaporthe oryzae, as exemplified by secreted and volatile organic metabolome-mediated mycelial growth inhibition. GC-MS analysis of the volatilome of M. testaceum indicated the abundance of antimicrobial compounds. Bacterization of rice seedlings showed phenotypic traits of MAMP-triggered immunity (MTI), over-expression of OsNPR1 and OsCERK, and the consequent blast suppressive activity. Strikingly, M. testaceum induced the transcriptional tradeoff between physiological growth and host defense pathways as indicated by up- and downregulated DEGs. Coupled with its plant probiotic features and the defense elicitation activity, the present study paves the way for developing Microbacterium testaceum-mediated bioformulation for sustainably managing rice blast disease.
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BACKGROUND: Chronic headache greatly affects the quality of life and also constitutes a significant burden on the health system. OBJECTIVE: The objective of this study was to evaluate the feasibility of telephone-based follow-up in a cohort of headache patients in India. MATERIALS AND METHODS: This was a longitudinal cohort study of patients with episodic headache with one physical visit in the neurology outpatient services in the last year. Two neurologists conducted the telephone follow up (TFU) of included patients 12 weeks apart. We evaluated the following: (1) objective characterization of headache, (2) coexistent depression and anxiety, (3) patient satisfaction, (4) treatment adherence, and (5) changes in medications. RESULTS: A total of 214 out of 274 eligible patients were included in the cohort. The mean age was 31.74 ± 7.77 years (18-45), and 164 (77%) were females. Migraine without aura was the most common diagnosis in 159 (74%). The mean disease duration was 78.01 ± 70.15 months (8-360). Concurrent depression and anxiety were noted in 87 (40.6%) and 45 (21%) of the patients, respectively. There was a significant improvement in the headache frequency (23.82 vs. 1.06, P < 0.001), severity (7.21 vs. 2.62, P = 0.032), and Headache Impact 6-item score (58.12 vs. 38.01, P = 0.014) at baseline and second follow-up. The satisfaction level to TFU in the first and second interviews was 94.4% and 97.2%, respectively. CONCLUSION: Telephone-based follow-up is a feasible alternative for repeat outpatient consultation of headache patients.
Subject(s)
Feasibility Studies , Patient Satisfaction , Telephone , Humans , Female , Male , Adult , Longitudinal Studies , India/epidemiology , Adolescent , Middle Aged , Young Adult , Depression/epidemiology , Anxiety/epidemiology , Headache , Follow-Up Studies , Headache Disorders/therapyABSTRACT
Angiotensin-converting enzyme I (ACE I) is a zinc-containing metallopeptidase involved in the renin-angiotensin system (RAAS) that helps in the regulation of hypertension and maintains fluid balance otherwise, which results in cardiovascular diseases (CVDs). One of the leading reasons of global deaths is due to CVDs. RAAS also plays a central role in maintaining homeostasis of the CV system. The commercial drugs available to treat CVDs possess several fatal side effects. Hence, phytochemicals like peptides having plant-based origin should be explored and utilized as alternative therapies. Soybean is an important leguminous crop that simultaneously possesses medicinal properties. Soybean extracts are used in many drug formulations for treating diabetes and other disorders and ailments. Soy proteins and its edible products such as tofu have shown potential inhibitory activity against ACE. Thus, this review briefly describes various soy proteins and products that can be used to inhibit ACE thereby providing new scope for the identification of potential candidates that can help in the design of safer and natural treatments for CVDs.
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Recent research in plant epigenetics has increased our understanding of how epigenetic variability can contribute to adaptive phenotypic plasticity in natural populations. Studies show that environmental changes induce epigenetic switches either independently or in complementation with the genetic variation. Although most of the induced epigenetic variability gets reset between generations and is short-lived, some variation becomes transgenerational and results in heritable phenotypic traits. The short-term epigenetic responses provide the first tier of transient plasticity required for local adaptations while transgenerational epigenetic changes contribute to stress memory and help the plants respond better to recurring or long-term stresses. These transgenerational epigenetic variations translate into an additional tier of diversity which results in stable epialleles. In recent years, studies have been conducted on epigenetic variation in natural populations related to various biological processes, ecological factors, communities, and habitats. With the advent of advanced NGS-based technologies, epigenetic studies targeting plants in diverse environments have increased manifold to enhance our understanding of epigenetic responses to environmental stimuli in facilitating plant fitness. Taking all points together in a frame, the present review is a compilation of present-day knowledge and understanding of the role of epigenetics and its fitness benefits in diverse ecological systems in natural populations.
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Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.
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Soybean is a predominantly self-pollinated crop. It is also one of the important oilseed legumes. Soybean is an excellent crop having industrial, traditional, culinary, feeding, and cultural roles. Genetic diversity in breeding programs is of prime importance as it ensures the success of any breeding by enhancing the outcomes and results of the plants. The phenomenon wherein the progeny exhibits greater biomass (yield) and a faster rate of development and fertility than its parents is referred to as heterosis. As of now, heterosis is mainly limited to the trait of seed yield and is considered the basis for the development of better (superior) varieties. Male sterility (MS) is extensively used for the production of seeds and the improvement of crops coupled with the traditional breeding programs and molecular technology. Therefore, deployment of MS and heterosis in breeding soybean could yield better outcomes. This review aims to focus on two aspects, namely, MS and heterosis in soybean with its scope for crop improvement.
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Magnaporthe grisea (T.T. Herbert) M.E. Barr is a major fungal phytopathogen that causes blast disease in cereals, resulting in economic losses worldwide. An in-depth understanding of the basis of virulence and ecological adaptation of M. grisea is vital for devising effective disease management strategies. Here, we aimed to determine the genomic basis of the pathogenicity and underlying biochemical pathways in Magnaporthe using the genome sequence of a pearl millet-infecting M. grisea PMg_Dl generated by dual NGS techniques, Illumina NextSeq 500 and PacBio RS II. The short and long nucleotide reads could be draft assembled in 341 contigs and showed a genome size of 47.89 Mb with the N50 value of 765.4 Kb. Magnaporthe grisea PMg_Dl showed an average nucleotide identity (ANI) of 86% and 98% with M. oryzae and Pyricularia pennisetigena, respectively. The gene-calling method revealed a total of 10,218 genes and 10,184 protein-coding sequences in the genome of PMg_Dl. InterProScan of predicted protein showed a distinct 3637 protein families and 695 superfamilies in the PMg_Dl genome. In silico virulence analysis revealed the presence of 51VFs and 539 CAZymes in the genome. The genomic regions for the biosynthesis of cellulolytic endo-glucanase and beta-glucosidase, as well as pectinolytic endo-polygalacturonase, pectin-esterase, and pectate-lyases (pectinolytic) were detected. Signaling pathways modulated by MAPK, PI3K-Akt, AMPK, and mTOR were also deciphered. Multicopy sequences suggestive of transposable elements such as Type LTR, LTR/Copia, LTR/Gypsy, DNA/TcMar-Fot1, and Type LINE were recorded. The genomic resource presented here will be of use in the development of molecular marker and diagnosis, population genetics, disease management, and molecular taxonomy, and also provide a genomic reference for ascomycetous genome investigations in the future.