The Combined Effect of Robot-assisted Therapy and Activities of Daily Living Training on Upper Limb Recovery in Persons With Subacute Stroke: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the effectiveness of robot-assisted therapy (RAT) followed by activities of daily living (ADL) training in comparison with conventional rehabilitation therapy (CRT) and ADL training in individuals with subacute stroke. DESIGN: A single-blind, 2-arm, parallel-group, open-level, randomized controlled trial. SETTING: A tertiary care teaching hospital in India. PARTICIPANTS: Forty-four persons (n=44) with first-ever stroke (in subacute stage) were enrolled from August 2021 to July 2023. INTERVENTION: Participants in the RAT group (n=22) received RAT for 30 minutes, followed by ADL training for 30 minutes. In contrast, participants in the CRT group (n=22) received CRT (30 minutes) followed by ADL training (30 minutes). Both groups received allocated interventions for 15 days over 3 weeks (5 days/week, 3 weeks). MAIN OUTCOME MEASURES: Primary outcome: Motor domain score of the Fugl-Meyer Assessment scale for upper extremity (FMA-UE). SECONDARY OUTCOMES: the other domains scores of FMA-UE (UL -sensation, -joint motions, -joint pain); Modified Ashworth Scale (MAS) (spasticity); hand-function (HF) and ADL-domain scores of the stroke impact scale (SIS); WHOQQL-BREF questionnaires (QOL). Participants were assessed at enrolment and follow-up at 3, 6, and 12 weeks. RESULTS: Persons who received RAT and ADL training reported significant improvement (P<.05) in UL motor function (mean difference [MD]=3.54;(95% confidence interval [CI]: 1.28 to 5.79]), UL passive joint motions (MD=2.54; [95% CI: 1.56 to 3.52]), SIS-HF (MD=6.37;[95% CI: 4.75 to 7.99]), SIS-ADL (MD=7.13 [95% CI: 3.52 to 8.74]), and in all domains of WHOQOL-BREF (except environmental domain) compared with persons who received CRT and ADL training at 12 weeks. CONCLUSIONS: The findings indicate that RAT followed by ADL training is more effective than CRT followed by ADL training in motor improvement, SIS-HF, SIS-ADL, and QOL at 12 weeks.

Organophosphorus poisoning induced delayed neurotoxicity: a report of two cases.

INTRODUCTION: Organophosphorus compounds (OPC) are one of the most commonly used pesticides worldwide and are often misused for suicidal poisoning due to their easy availability. Acute manifestations and management of organophosphorus (OP) poisoning have been reported several times. Organophosphorus-induced delayed neurotoxicity (OPIDN) is a rare delayed presentation of OP poisoning that involves central-peripheral distal axonopathy. CASE PRESENTATION: In this study, we report two cases of OPIDN developed after a few weeks of OP poisoning. Clinical features, electrodiagnostic study findings, and rehabilitative measures adopted for the patients and their follow-up have been described in the report. DISCUSSION: Organophosphorus (OP) poisoning may rarely produce features of delayed neurotoxicity, which may gradually appear after acute cholinergic symptoms. This report shows the importance of considering the delayed presentation of possible OPC toxicity in patients with neurological symptoms and a history of OPC exposure.

Platelet-rich plasma injection in the treatment of patellar tendinopathy: a systematic review and meta-analysis.

PURPOSE: The objective of the study was to assess the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of patellar tendinopathy. METHODS: The PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for clinical trials which compared PRP injection with other 'active treatment' interventions ('Non-PRP' injection and 'No-injection' treatments) or 'No-active treatment' interventions. Randomized and non-randomized clinical trials that had been published up to 15 November 2021, were included in the meta-analysis. The primary outcome, pain relief, was measured on a 'visual analog scale.' Secondary outcomes were knee functional activities and quality of life (QoL). The PRISMA guidelines were followed throughout the study. RESULTS: Eight comparative studies were identified for inclusion in the meta-analysis. Assessment of these studies revealed that there were no significant differences in pain relief, functional outcomes, and QoL in the short, medium, and long term between PRP injection and Non-PRP injection interventions. Similarly, comparison of PRP injection to the No-active treatment intervention showed no differences in short- and medium-term pain relief. However, when PRP injection was compared to the No-injection treatment intervention extracorporeal shock wave therapy (ECWT), the former was found to be more effective in terms of pain relief in the medium term (mean difference [MD] - 1.50; 95% confidence interval [CI] - 2.72 to - 0.28) and long term (MD - 1.70; 95% CI, - 2.90 to - 0.50) and functional outcomes in the medium term (MD 13.0; 95% CI 3.01-22.99) and long term (MD 13.70; 95% CI 4.62-22.78). CONCLUSIONS: In terms of pain relief and functional outcomes, the PRP injection did not provide significantly greater clinical benefit than Non-PRP injections in the treatment of patellar tendinopathy. However, in comparison with ESWT, there was a significant benefit in favor of PRP injection.

Neuropathic Pain in Hospitalized Patients With COVID-19: A Prospective Case Series.

Objective: To report the demographic and clinical characteristics of 8 patients hospitalized with COVID-19 and presenting with neuropathic pain (NeuP). Design: A prospective case series with 1-month follow-up. Settings: COVID-19-dedicated wards of a tertiary care center. Participants: We included 8 consecutive cases of laboratory-confirmed cases of COVID-19 (by reverse transcription polymerase chain reaction) who presented with NeuP during the course of their acute hospitalization (N=8). Interventions: Not applicable. Main Outcome Measures: A verbal rating scale was used to assess NeuP severity at presentation and at 1-month follow-up. The Douleur Neuropathique 4 questionnaire was used to diagnose NeuP at presentation. Results: Most patients were diagnosed as moderate to severe COVID-19 (6/8) and presented with mild to moderate NeuP (6/8). A substantial proportion of patients (4/8) displayed persistence of mild pain symptoms at 1-month follow-up. Furthermore, participants displayed a favorable response to gabapentinoids with or without antidepressants. Conclusion: NeuP is a less commonly encountered symptom of COVID-19, but its early diagnosis and prompt management are of utmost importance. More studies including a larger cohort and longer follow-up are recommended for better understanding of COVID-19-associated NeuP.

Insulin, Insulin Everywhere: A Rare Case Report of Rabson-Mendenhall Syndrome.

Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond appropriately to the hormone insulin. Insulin resistance impairs blood sugar regulation and ultimately leads to diabetes mellitus. A 19-year-old male presented with joint pain, blurring of vision, and generalized weakness. Investigations revealed hyperglycemia (random blood sugar (RBS) > 625 mg/dL, glycosylated hemoglobin (HbA1c) 18%), as well as sugars, protein, and ketone bodies in urine routine examination. An ultrasound of the abdomen was normal. Cardiac status was normal. Based on the clinical features, particularly the head to toe examination, skin changes, and the onset of type 2 diabetes mellitus, RMS syndrome was considered. The joint pain was alleviated with intravenous tramadol. Actrapid®, a fast-acting insulin, was given to control sugar levels, along with metformin. Vitamin B12 and pregabalin were also supplemented. A dermatological cream containing ammonium chloride, calcium lactate, glycerin, potassium chloride, sodium dihydrogen phosphate, and urea was given for skincare. It is an extremely rare disease with a frequency of fewer than one million people worldwide. Most patients survive only up to 15 years of age, although some can live into their third decade of life. Hepatic gluconeogenesis and fatty acid oxidation are affected, leading to ketoacidosis. The progression is much faster in RMS. In RMS, the genetic defect affects the insulin receptor (INSR) gene transcription with non-sense mutations and causes splicing defects. This results in premature chain termination and eventually to lower amounts of the insulin receptor messenger ribonucleic acid (mRNA). Ultimately, the number and density of insulin receptors in the plasma membrane are smaller, making the cells resistant to insulin. Herein, we report the case of a 19-year-old patient with RMS who was treated in our hospital, leading to a successful improvement in symptoms and discharge of the patient.

Role of proteomics in biomarker discovery: prognosis and diagnosis of neuropsychiatric disorders.

One of the major concerns of modern society is to identify putative biomarkers that serve as a valuable early diagnostic tool to identify a subset of patients with increased risk to develop neuropsychiatric disorders. Today, proteomic approaches have opened new possibilities in diagnostics of devastating disorders like neuropsychiatric disorders. Proteomics-based technologies for biomarker discovery have been promising because alterations in protein expression and its protein abundance, structure, or function can be used as indicators of pathological abnormalities prior to development of clinical symptoms of neuropsychiatric disorders. This is because using mass spectrometry spectra analysis, it is possible to identify biomarkers of these diseases based on the identification of proteins in body fluids that is easily available, for example, the cerebrospinal fluid, serum, or blood. An ideal biomarker should be present in the blood before the disease is clinically confirmed, have high sensitivity and specificity, and be reproducible. Despite of advances in the proteomic technologies, it has not yielded significant clinical application in neuropsychiatry research. The review discusses overall proteomic approaches for elucidating molecular mechanisms and its applicability for biomarker discovery, diagnosis, and therapeutics of psychiatric disorders such as anxiety, depression, Alzheimer's disease, schizophrenia, and bipolar disorder. In addition, we have also discussed issues and challenges regarding the implementation of proteomic approaches as a routine diagnostic tool in the clinical laboratory in context with neuropsychiatric disorders.

Role of proteomics in biomarker discovery and psychiatric disorders: current status, potentials, limitations and future challenges.

Proteomic approaches have advanced clinical research towards more reliable, sensitive and specific biological diagnostic markers for diseases. Mood disorders are most difficult to diagnose and very much prevalent in society; hence, their proper diagnosis becomes essential. Despite tremendous research efforts to dissect the neurobiological basis of psychiatric disorders, the diagnosis and evaluation for such diseases is still poor. Biomarker discovery in psychiatry research has been accelerated by proteomic technologies, accepting the challenges in order to meet disease state-related investigations. Proteomics-based research for disease-specific protein signatures is expected to give a new direction in psychiatry research. Therefore, this may become a more powerful tool to predict the development, course and outcome of the disease towards personalized psychiatric ailments. The review discusses the role of proteomics in elucidating mechanisms of psychiatric disorders, current status, prospects, limitations and new possibilities towards a strong diagnostic tool in the clinical laboratory.

Glycyrrhiza glabra (Linn.) and Lavandula officinalis (L.) cell suspension cultures-based biotransformation of ß-artemether.

The biotransformation of ß-artemether (1) by cell suspension cultures of Glycyrrhiza glabra and Lavandula officinalis is reported here for the first time. The major biotransformed product appeared as a grayish-blue color spot on thin-layer chromatography (TLC) with transparent crystal-like texture. Based on its infrared (IR) and (1)H nuclear magnetic resonance (NMR) spectra, the product was characterized as a tetrahydrofuran (THF)-acetate derivative (2). The highest conversion efficiencies of 57 and 60% were obtained when 8-9-day-old cell suspensions of G. glabra and L. officinalis were respectively fed with 4-7 mg of compound 1 in 40 ml of medium per culture and the cells were harvested after 2-5 days of incubation. The addition of compound 1 at the beginning of the culture cycle caused severe growth depression in a dose-dependent manner, resulting in poor bioconversion efficiency of ~25% at 2-5 mg/culture dose only.

Involvement of nitric oxide in maneb- and paraquat-induced Parkinson's disease phenotype in mouse: is there any link with lipid peroxidation?

The study aimed to investigate the involvement of nitric oxide (NO) in maneb (MB)- and paraquat (PQ)-induced Parkinson's disease (PD) phenotype in mouse and its subsequent contribution to lipid peroxidation. Animals were treated intraperitoneally with or without MB and PQ, twice a week for 3, 6 and 9 weeks. In some sets of experiments (9 weeks treated groups), the animals were treated intraperitoneally with or without inducible nitric oxide synthase (iNOS) inhibitor-aminoguanidine, tyrosine kinase inhibitor-genistein, nuclear factor-kappa B (NF-kB) inhibitor-pyrrolidine dithiocarbamate (PDTC) or p38 mitogen activated protein kinase (MAPK) inhibitor-SB202190. Nitrite content and lipid peroxidation were measured in all treated groups along with respective controls. RNA was isolated from the striatum of control and treated mice and reverse transcribed into cDNA. RT-PCR was performed to amplify iNOS mRNA and western blot analysis was done to check its protein level. MB- and PQ-treatment induced nitrite content, expressions of iNOS mRNA and protein and lipid peroxidation as compared with respective controls. Aminoguanidine resulted in a significant attenuation of iNOS mRNA expression, nitrite content and lipid peroxidation demonstrating the involvement of nitric oxide in MB- and PQ-induced lipid peroxidation. Genistein, SB202190 and PDTC reduced the expression of iNOS mRNA, nitrite content and lipid peroxidation in MB- and PQ-treated mouse striatum. The results obtained demonstrate that nitric oxide contributes to an increase of MB- and PQ-induced lipid peroxidation in mouse striatum and tyrosine kinase, p38 MAPK and NF-kB regulate iNOS expression.

Biotransformation of artemisinin using cell suspension cultures of Catharanthus roseus (L.) G.Don and Lavandula officinalis L.

Artemisinin, an antimalarial compound, at 5 mg/40 ml, was transformed by cell suspension cultures of Catharanthus roseus (L.) G.Don and Lavandula officinalis L. into deoxyartemisinin with yields >78% (3.93 mg deoxyartemisinin from 5 mg artemisinin). Maximum conversion (78.6 and 78%) occurred after 6 and 7 days of adding artemisinin to 20 and 9 days old cultures of C. roseus and L. officinalis, respectively. The procedure was scaled up by and 500 mg artemisinin was transformed into 390 mg deoxyartemisinin. Addition of artemisinin at the beginning of the culture cycle resulted in >50% reduction in dry biomass production with no bioconversion. Conversion of artemisinin occurred intracellularly followed by leaching of the product into the medium.

Gene expression profiles of mouse striatum in control and maneb + paraquat-induced Parkinson's disease phenotype: validation of differentially expressed energy metabolizing transcripts.

The present study was undertaken to investigate the gene expression patterns of the striatum of control and maneb + paraquat-induced Parkinson's disease (PD) phenotype in mouse to identify the differentially expressed transcripts. The animals were treated with and without maneb (30 mg/kg, i.p.) + paraquat (10 mg/kg, i.p.), twice a week, for 3, 6, and 9 weeks. The RNA was isolated from control and treated mouse striatum and reverse transcribed, and equal quantities of labeled cDNA were mixed and hybridized with mouse 15 k arrays. Comparative transcription patterns showed the time of exposure dependent alteration in the expression of several transcripts associated with various pathways. RT-PCR reconfirmed the differential expression of some energy metabolizing transcripts. The study provides maneb + paraquat-induced differential expression of many transcripts using high-density microarray approach. Few transcripts, which were previously not reported to be associated with neuronal degeneration, were also identified. The results obtained thus suggest that maneb + paraquat induce neurotoxicity in the striatum in a time of exposure dependent manner via multiple pathways and defective energy metabolism could play a critical role.

Nicotine and caffeine-mediated modulation in the expression of toxicant responsive genes and vesicular monoamine transporter-2 in 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease phenotype in mouse.

Epidemiological evidence revealed that cigarette smokers and coffee drinkers have lower risk of Parkinson's disease (PD). Nicotine inhibits monoamine oxidase activity, and induces expression of neurotrophic factors and nicotinic acetylcholinergic receptors. However, caffeine is capable of antagonizing adenosine A(2A) receptor. Toxicant responsive enzymes and vesicular monoamine transporter-2 (VMAT-2) play critical roles in chemically induced PD. Despite some known functions, the effects of nicotine and caffeine on the expression and activity of toxicant responsive genes and on VMAT-2 are still not known. The study was therefore undertaken to investigate the effect of nicotine and caffeine on the expression and activity of toxicant responsive genes, i.e., CYP1A1, CYP2E1, GST-ya, GST-yc, GSTA4-4 and VMAT-2 in the striatum of control and MPTP-induced PD phenotype in mouse. The animals were treated intraperitoneally daily with nicotine (1 mg/kg) or caffeine (20 mg/kg) for 8 weeks, followed by 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg)+nicotine or caffeine for 4 weeks. MPTP significantly attenuated CYP1A1 and VMAT-2, and augmented CYP2E1, GST-ya, GST-yc and GSTA4-4 expression/activity. Nicotine or caffeine-treated animals showed significant restoration against most of the MPTP-induced alterations. The results obtained thus suggest that nicotine and caffeine modulate MPTP-induced alterations in CYP1A1, CYP2E1, GST-ya, GST-yc, GSTA4-4 and VMAT-2 expression/activity.

Identification of differentially expressed proteins in striatum of maneb-and paraquat-induced Parkinson's disease phenotype in mouse.

Behavioral, phenotypic and biochemical changes induced by maneb+paraquat (MB+PQ) in experimental animals have shown their role in the etiologies of Parkinson's disease (PD); however, MB+PQ induced neuronal damage at genome and proteome level have not yet been clearly understood. The present study was undertaken to investigate the differential protein expression patterns in control and MB+PQ treated mouse striatum and to identify differentially expressed proteins. Animals were treated with and without MB+PQ, twice a week for three, six and nine weeks and proteome profiles of striatum were compared. Three differentially expressed proteins were identified as complexin-I, alpha-enolase and glia maturation factor-beta (GMF-beta) using 2D-PAGE and mass spectrometry. The differential expressions were also confirmed at transcription level by semi-quantitative RT-PCR. The results suggest the involvement of complexin-I, alpha-enolase and GMF-beta in MB+PQ induced PD phenotype in mouse.

Involvement of endogenous nitric oxide in myeloperoxidase mediated benzo(a)pyrene induced polymorphonuclear leukocytes injury.

The present study was undertaken to investigate the involvement of nitric oxide in the augmentation of benzo(a)pyrene induced cellular injury in polymorphonuclear leukocytes (PMNs). Polymorphs were isolated from the blood collected from Wistar rats treated with and without benzo(a)pyrene (50mg/kg, i.p.) through cardiac puncture. Catalase, superoxide dismutase (SOD), glutathione-s-transferase (GST), myeloperoxidase (MPO) and nitrite content were estimated in PMNs using standard procedures. Inducible nitric oxide synthase (iNOS) and cytochrome P-4501A1 (CYP1A1) expression in PMNs were also analyzed in presence or absence of nitric oxide synthase (NOS) inhibitors, aminoguanidine (AG, 5mM) and L-NG nitro L-arginine methyl ester (L-NAME, 1mM). A significant augmentation was observed in the nitrite content, activities of superoxide dismutase, MPO and GST and the expressions of iNOS and CYP1A1, however, catalase activity was attenuated in PMNs of benzo(a)pyrene treated rats as compared with their respective controls. AG and L-NAME resulted in a significant attenuation in nitrite content, MPO activity and iNOS expression; however, no significant alteration was observed in CYP1A1 expression. CYP1A1 inhibitor alpha-naphthoflavone inhibited the expression of iNOS in PMNs of benzo(a)pyrene treated animals significantly. The results obtained thus suggest that CYP1A1 induces iNOS expression leading to the generation of endogenous nitric oxide (NO) that could be responsible for the augmentation of myeloperoxidase-mediated benzo(a)pyrene-induced injury in PMNs.

Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson's disease phenotype in mouse: mechanism of neurodegeneration.

Parkinson's disease (PD) is a progressive neurodegenerative disorder contributed by the combination of age, genetic and environmental factors. Several studies have clearly shown increase in the incidences of PD in the rural environments and hypothesized the involvement of pesticides such as paraquat and maneb in neurodegeneration. These studies have prompted researchers to develop paraquat and maneb models to study the effect of co-treatment of maneb and paraquat on neuronal toxicity; however, the mechanism underlying maneb and paraquat co-treatment induced neuronal toxicity has not yet been clearly understood. The involvement of cytochrome P4502E1 and glutathione S-transferases A4-4 enzymes in the detoxification of several pesticides such as atrazine, fenamirol, organophosphorous insecticide parathion, methoxychlor, diethyl dithiocarbamate and paraquat has been known. The contribution of CYP2E1 and GSTA4-4 in neuronal toxicity has also been reported. The present study was therefore undertaken to investigate the mechanism of maneb- and paraquat-induced neurodegeneration by estimating the level of antioxidant defense enzymes in the striatum and measuring the differential expressions of CYP2E1 and GSTA4-4 genes. Animals were treated with and without maneb (30 mg/kg, i.p.) or paraquat (10 mg/kg, i.p.) either alone or in combination in exposure time-dependent manner. A significant increase in catalase, glutathione S-transferase and lipid peroxidation in the striatum was found following 3, 6 and 9 weeks of co-treatment as compared with individual treatment or controls. Individual treatment of maneb or paraquat did not exhibit any significant alteration in CYP2E1 and GSTA4-4 expression up to 6 weeks; however, an augmentation in CYP2E1 and GSTA4-4 expression was observed in the animals exposed to maneb or paraquat for 9 weeks. Augmentation in the expression of CYP2E1 and GSTA4-4 was more pronounced in the animals treated with maneb and paraquat in combination for nine weeks. A significant reduction in the augmented lipid peroxidation in the striatum was observed when the striatum was pre-administered with CYP2E1 inhibitors; however, glutathione pre-administration induced lipid peroxidation. Results obtained from the present investigation suggest the involvement of CYP2E1 and GSTA4-4 in the augmentation of the lipid peroxidation thereby enhancing neurodegeneration.