Telerehabilitation: Exploring the Untapped Potential.

Telerehabilitation is a burgeoning field that holds immense promise in revolutionizing the delivery of rehabilitation services. Defined as a branch of telecommunication utilizing technologies such as the internet, it facilitates remote interaction between healthcare providers and patients, transcending geographical barriers. This method proves invaluable in patient assessment, counseling, and treatment across various medical domains, including physical therapy, speech therapy, psychotherapy, and occupational therapy. Particularly beneficial for individuals with disabilities or those unable to access traditional healthcare facilities, telerehabilitation mitigates the constraints of time and cost associated with travel. This paper explores the evolution, types, uses, and research findings in telerehabilitation, shedding light on its transformative potential in health care.

Integrated transcriptomics and histopathology approach identifies a subset of rejected donor livers with potential suitability for transplantation.

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.

Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-ß is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-ß signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

Analysis of Cutaneous Adverse Drug Reactions (ADR) Reported at an ADR Monitoring Center of a Tertiary Care Teaching Institute in Central India.

Background Cutaneous adverse drug reactions (ADRs) are among the most frequent ADRs. Knowledge of the pattern of cutaneous ADRs (CADRs) and causal drugs helps prevent and reduce the incidence of CADR, which in turn reduces the incidence of hospitalization and expenses for the patient. Objectives To analyze CADR according to demographic profile, morphological pattern, causative drugs, severity, and outcome in patients suffering from CADRs. Materials and methods Retrospective data analysis was conducted in the Adverse Drug Reaction Monitoring Centre (AMC) of the tertiary care teaching institute between February 2020 and September 2023 under the Pharmacovigilance Program of India (PvPI). All ADRs reported were analyzed based on the following parameters: total number of ADRs reported, number of CADRs, information related to demographic parameters, the clinical presentation of CADRs, and suspected medication. Causality assessment was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Severity was assessed using a modified Hartwig and Seigel scale. Results A total of 125 CADRs were analyzed. Considering the gender-wise distribution, 65 females and 60 males suffered from CADR. The most common drug category responsible for CADRs was antimicrobials (63.2%), followed by topical agents (12.8%). Maculopapular rash (33.6%) was the most common presenting symptom, followed by itching (27.2%). Few patients suffered from serious CADRs such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Conclusion A wide clinical spectrum of CADRs ranging from maculopapular rash to fixed-drug eruption to serious SJS was observed in our study. The most common causative agents for CADRs were antimicrobials, followed by topical agents and NSAIDs. For early diagnosis and management of CADRs, it is critical to have data on the potential cutaneous adverse effects of commonly used drugs, to educate the patients regarding common early symptoms of drug reactions (e.g., erythematous rash, edema, urticaria, mucosal erosions, itching, burning of skin, etc.), and to monitor the patient, especially during the start of therapy. To ease the burden of CADRs, a therapeutic plan of anticipating, avoiding, recognizing, and responding to ADRs should be implemented.

Investigating the role of an immediate early gene FOS as a potential regulator of autophagic response to hypoglycemia in embryonic hypothalamic neurons.

Hypoglycemia-associated autonomic failure (HAAF) is a well-established complication of diabetes. Although HAAF has serious outcomes such as recurrent morbidity, coma, and death, the mechanisms of HAAF and its pathological components are largely unknown. Our previous studies have revealed that hypoglycemia is associated with the upregulation of an immediate early gene - FOS. In addition, it is documented that glucose deprivation activates neuronal autophagic activities. Therefore, the present study aimed to identify the role of FOS and one of the core components of the autophagy pathway, Beclin-1 (encoded by the BECN1 gene), in the regulation of autophagic mechanisms in embryonic hypothalamic neurons in response to hypoglycemic conditions. Embryonic Mouse Hypothalamic Cell Line N39 (mHypoE-N39 or N39) was cultured in reduced concentrations of glucose (2000, 900, 500, and 200 mg/L). Gene and protein expression, as well as immunofluorescence studies on autophagy were conducted under different reduced glucose concentrations in N39 hypothalamic neurons with and without FOS and BECN1 gene knockdowns (KD). The outcomes of the present study have demonstrated a significant increase in autophagosome formation and subsequent lysosomal degradation in the hypothalamic neurons in response to reduced glucose concentrations. This hypoglycemic response appears to be lowered to a similar extent in the FOS KD and BECN1 KD cells, albeit insignificantly from the negative control, is indicative of the involvement of FOS in the autophagic response of hypothalamic neurons to hypoglycemia. Moreover, the KD cells exhibited a change in morphology and reduced cell viability compared with the control cells. Our findings suggest that reduced FOS expression could potentially be associated with impaired autophagic activities that are dependent on BECN1, which could lead to decreased or blunted hypothalamic activation in response to hypoglycemia, and this, in turn, may contribute to the development of HAAF.

Rehabilitation of a Chronic Guillain-Barré Syndrome Patient With Vibratory Motor Stimulation of Dorsiflexors: A Case Report.

There are various reports describing physiotherapy rehabilitation in Guillain-Barré syndrome (GBS) but the use of current to rehabilitate GBS patients has remained an untouched topic. To elaborate on this work, we describe a case report focusing on the intervention plan for the rehabilitation of a chronic GBS case by the use of vibratory motor stimulation (VMS) current. The study aimed to describe the therapeutic application of VMS current in improving muscle power of dorsiflexors and overall outcome measures in a case of GBS presenting in a tertiary care hospital in North India. A 29-year-old male patient came to Teerthanker Mahaveer University Hospital and consulted in the Department of Physiotherapy after 1.4 years of being diagnosed with acute motor axonal neuropathy-type GBS. Rehabilitation of this case included strengthening exercises of the upper and lower limbs along with balance exercises. Specifically, in this case, we gave VMS current after assessing the muscle power of the dorsiflexors, which was found to be grade-0 over the bilateral dorsiflexors, combined with passive dorsiflexion. Different outcome measures were used for assessment, including manual muscle testing, functional independence measurement, and the Berg Balance Scale. Improvement in the patient's condition was observed in his outcome measures after two months of treatment. There was an overall improvement in the muscle power of our patient's dorsiflexors, where muscle power was upgraded from grade-0 to grade-I and grade-I+ in the bilateral lower limbs by the use of VMS current. This study marks a novel application of VMS to the dorsiflexors of a GBS patient, yielding positive outcomes in upgrading muscle power grades from grade-0 to grade-I and grade-I+. Further research is needed to confirm VMS efficacy as an early intervention in GBS patient rehabilitation.

Mitochondria in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-ß and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment.

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice.

PURPOSE: Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. METHODS: A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. RESULTS: After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. CONCLUSION: Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.

Cholesterol deficiency as a mechanism for autism: A valproic acid model.

Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. Therefore, we examined the effect of VPA exposure on regulation of cholesterol homeostasis in the human microglial clone 3 (HMC3) cell line and the human neuroblastoma cell line SH-SY5Y. HMC3 and SH-SY5Y cells were each incubated in increasing concentrations of VPA, followed by quantification of mRNA and protein expression of cholesterol transporters and cholesterol metabolizing enzymes. Cholesterol efflux was evaluated using colorimetric assays. We found that VPA treatment in HMC3 cells significantly reduced ABCA1 mRNA, but increased ABCG1 and CD36 mRNA levels in a dose-dependent manner. However, ABCA1 and ABCG1 protein levels were reduced by VPA in HMC3. Furthermore, similar experiments in SH-SY5Y cells showed increased mRNA levels for ABCA1, ABCG1, CD36, and 27-hydroxylase with VPA treatment. VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.

Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat.

Neurogenic hypertension stems from an imbalance in autonomic function that shifts the central cardiovascular control circuits toward a state of dysfunction. Using the female spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat model, we compared the transcriptomic changes in three autonomic nuclei in the brainstem, nucleus of the solitary tract (NTS), caudal ventrolateral medulla, and rostral ventrolateral medulla (RVLM) in a time series at 8, 10, 12, 16, and 24 wk of age, spanning the prehypertensive stage through extended chronic hypertension. RNA-sequencing data were analyzed using an unbiased, dynamic pattern-based approach that uncovered dominant and several subtle differential gene regulatory signatures. Our results showed a persistent dysregulation across all three autonomic nuclei regardless of the stage of hypertension development as well as a cascade of transient dysregulation beginning in the RVLM at the prehypertensive stage that shifts toward the NTS at the hypertension onset. Genes that were persistently dysregulated were heavily enriched for immunological processes such as antigen processing and presentation, the adaptive immune response, and the complement system. Genes with transient dysregulation were also largely region-specific and were annotated for processes that influence neuronal excitability such as synaptic vesicle release, neurotransmitter transport, and an array of neuropeptides and ion channels. Our results demonstrate that neurogenic hypertension is characterized by brainstem region-specific transcriptomic changes that are highly dynamic with significant gene regulatory changes occurring at the hypertension onset as a key time window for dysregulation of homeostatic processes across the autonomic control circuits.NEW & NOTEWORTHY Hypertension is a major disease and is the primary risk factor for cardiovascular complications and stroke. The gene expression changes in the central nervous system circuits driving hypertension are understudied. Here, we show that coordinated and region-specific gene expression changes occur in the brainstem autonomic circuits over time during the development of a high blood pressure phenotype in a rat model of human essential hypertension.

Atypical Morphology of a Typical Mycobacterial Infection.

A-24-year-old woman reported with asymptomatic facial lesions present for 6 months. Examination revealed two closely located nodules which were firm, nontender, slightly erythematosus with crusting over the left cheek (Figure 1A). There was no regional lymphadenopathy, and the systemic examination was within normal limits. The differential diagnosis included cutaneous leishmaniasis, keratoacanthoma, and basal cell carcinoma. Tissue smear from nodules failed to reveal Leishmania donovan bodies. The histopathologic examination revealed nonca-seating epithelioid granulomas with lymphocyte cuffing in the dermis (Figures 2A and 2B). Special staining performed with Ziehl-Neelsen and Periodic acid-Schiff (PAS) stains was negative. Tissue cultures for bacteria, mycobacteria, and fungi were also negative; however Mantoux test (MT) performed for latent tuberculosis was strongly positive. Sputum for acid fast bacilli was negative, and serology for human immuno-deficiency virus (HIV)-1 and HIV-2 was nonreactive. A chest x-ray and ultrasound of the abdomen did not reveal any abnormality. Although the morphology of skin lesions did not favor classic lupus vulgaris (LV), considering the endemicity of tuberculosis in India, positive results of Mantoux test, and a dermal epithelioid granuloma, the patient was prescribed antitubercular therapy (ATT), comprising isoniazid, rifampicin, ethambutol, and pyrazinamide. Dramatic response was observed after 2 months, and complete healing with residual scarring took place in next 4 months (Figure 1B).

Therapeutic Potential of P110 Peptide: New Insights into Treatment of Alzheimer's Disease.

Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer's disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-ß accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-ß generation and improving neuronal health by maintaining mitochondrial function in neurons.

Pesticide mediated silent neurotoxicity and its unmasking: An update on recent progress.

Being human's one of the most protected organs, brain is yet most vulnerable to xenobiotics exposure. Though pesticide-mediated neurotoxicity is well-explored, the fraternity of neurotoxicologists is less focused on the phenomenon of "silent" or "clinically undetectable" neurotoxicity. Silent neurotoxicity defines continual trivial changes in the nervous system that do not manifest any overt signs of toxicity unless unmasked by any natural or experimental event. Although this perception is not novel, insufficient experimental and epidemiological evidence makes it an outlier among toxicological research. A report in 2016 highlighted the need to investigate silent neurotoxicity and its potential challenges. The limited existing experimental data unveiled the unique responsiveness of neurons following silent neurotoxicity unmasking. Concerned studies have shown that low-dose developmental exposure to pesticides sensitizes the nigrostriatal dopaminergic system towards silent neurotoxicity, making it vulnerable to advanced cumulative neurotoxicity following pesticide challenges later in life. Therefore, conducting such studies may explain the precise etiology of pesticide-induced neurological disorders in humans. With no updates on this topic since 2016, this review is an attempt to acquaint the neurotoxicologist with silent neurotoxicity as a serious threat to human health, and proof-of-concept through a narrative using relevant published data so far with future perspectives.

Unilateral non-healing ulcers in zosteriform pattern.

Trigeminal trophic syndrome (TTS) is a rare disease that occurs after injury to the trigeminal nerve. Though this condition has been reported in the early 20th century, it is still a rare entity, with only around 200 cases reported so far. It characteristically presents with persistent facial ulceration with loss of sensation and paraesthesia along the distribution of the trigeminal nerve. We here report a case of TTS developing as a complication of herpes zoster, which possibly occurred due to the nerve damage caused by varicella-zoster virus.