Role of PON1 L55M Gene Polymorphism in Parkinson's Disease among North Indian Population.

BACKGROUND AND OBJECTIVES: The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. MATERIALS AND METHOD: Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. RESULTS: Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. CONCLUSION: There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

National plans and awareness campaigns as priorities for achieving global brain health.

Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all.

Field based research in the era of the pandemic in resource limited settings: challenges and lessons for the future.

The coronavirus pandemic that began in December 2019, has had an unprecedented impact on the global economy, health systems and infrastructure, in addition to being responsible for significant mortality and morbidity worldwide. The "new normal" has brought along, unforeseen challenges for the scientific community, owing to obstructions in conducting field-based research in lieu of minimizing exposure through in-person contact. This has had greater ramifications for the LMICs, adding to the already existing concerns. As a response to COVID-19 related movement restrictions, public health researchers across countries had to switch to remote data collections methods. However, impediments like lack of awareness and skepticism among participants, dependence on paper-based prescriptions, dearth of digitized patient records, gaps in connectivity, reliance on smart phones, concerns with participant privacy at home and greater loss to follow-up act as hurdles to carrying out a research study virtually, especially in resource-limited settings. Promoting health literacy through science communication, ensuring digitization of health records in hospitals, and employing measures to encourage research participation among the general public are some steps to tackle barriers to remote research in the long term. COVID-19 may not be a health emergency anymore, but we are not immune to future pandemics. A more holistic approach to research by turning obstacles into opportunities will not just ensure a more comprehensive public health response in the coming time, but also bolster the existing infrastructure for a stronger healthcare system for countries.

Tubercular Mediastinal Lymphadenopathy Presenting as an Isolated Unilateral Vocal Cord Palsy and the "Sail" Sign.

Tuberculosis continues to remain a major public health challenge, especially in low- and middle-income countries. Unilateral vocal cord palsy in adults as the sole manifestation of tubercular mediastinal lymphadenopathy has been rarely reported. A 22-year-old lady presented with a history of hoarseness of voice for the past month. The general physical examination revealed palpable lymph nodes in the left axilla. Axial CT sections at the level of the vocal cords demonstrated dilation of the right laryngeal ventricle and mild anteromedial deviation of the ipsilateral arytenoid cartilage ("sail" sign) suggestive of a right vocal cord palsy. Contrast-enhanced CT chest revealed right paratracheal, right hilar, and subcarinal lymph nodes with areas of central necrosis. She was started on anti-tubercular therapy and her voice completely improved after three months of treatment. The "Sail" sign on axial CT scans is a useful radiological sign for diagnosing unilateral vocal cord palsy. Rarely, compression of the recurrent laryngeal nerve by enlarged mediastinal lymph nodes due to tuberculosis can present with unilateral vocal cord palsy as the sole manifestation in adults.

Comprehensive amino acid composition analysis of seed storage proteins of cereals and legumes: identification and understanding of intrinsically disordered and allergenic peptides.

The seed storage proteins of cereal and legumes are the primary source of amino acids which are required for sustaining the nitrogen and carbon demands during germination and growth. Humans derive most of their dietary proteins from storage proteins in form of a wide variety of foods, for consumption. The amino acid content of most of these proteins is biased and the need for this biasness is not understood. The high abundance of proline, glutamine, and cysteine in cereals makes the gluten fraction viscoelastic. The cereal proteins have less charge and legume proteins have more charge on them. Their non-polar amino acid distribution has large variations. These characteristics are strongly responsible for the partial and complete unfolding of several domains of the storage proteins. Many of the storage proteins share a highly conserved structural feature within the cupin superfamily spread across all kingdoms of life. The intrinsically disordered viscoelastic proteins help in making dough which is vital for the quality of bread. Unfolded regions harbor more immunogenic sequences and cause food-related allergies and intolerance. We have discussed these properties in terms of comparison of cereal and legume storage protein sequences and allergy. Our study supports the findings that large disordered regions contain allergen-representative peptides. Interestingly, a high number of allergen-representative peptides were cleavable by digestive enzymes. Furthermore, unfolded storage proteins mimic microbial immunogens to induce a memory immune response. Results findings can be used to guide the understanding of immunological characteristics of storage proteins and may assist in treatment decisions for food allergy.Communicated by Ramaswamy H. Sarma.

A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

A comprehensive proteomic profiling of urinary exosomes and the identification of early non-invasive biomarker in patients with coronary artery disease.

Urinary small extracellular vesicles or exosomes (uEVs) source could be an emerging trove of biomarkers in coronary artery disease (CAD). It is a chronic inflammatory disease having a long asymptomatic phase of fatty-fibrous development in arteries leading to angina, myocardial infarction, and death. Our study was aimed at identifying differential protein expression profiling of uEVs in CAD. We collected urine samples of CAD patients (n = 41) age 18-65 years and gender matched healthy controls (n = 41). We isolated uEVs using differential ultracentrifugation. Further, uEV samples were characterized by western blotting exosome markers (Flotillin, TSG, CD63, and CD9), nano tracking analysis, and transmission and scanning electron microscopy. A total of 508 proteins were identified by iTRAQ-based mass spectrometry. We observed protein expression levels of AZGP1, SEMG1/2, ORM1, IGL, SERPINA5, HSPG2, prosaposin, gelsolin, and CD59 were upregulated, and UMOD, KNG1, AMBP, prothrombin, and TF were downregulated. Protein-protein interactions, gene ontology and pathway analysis were performed to functionally annotate identified uEVs proteins. A novel uEVs differential protein signature is shown. On validating UMOD protein by ELISA in two clinically different CAD, stable-CAD patients had lower levels than healthy controls whereas recent myocardial infarction patients had lowest. Our findings suggest UMOD importance as early diagnostic biomarker. SIGNIFICANCE: Coronary artery disease is a chronic inflammatory disease caused by gradual deposition of cholesterol and fat along with other proteins to develop plaque inside arteries. This further leads to blockage of artery, heart attack and death. There are no identifiable early biomarkers to diagnose this. For the first time, we have identified the differentially expressed proteins isolated from non-invasive uEV of CAD patients compared to healthy controls by using MS Orbitrap and iTRAQ labelling of peptides. We have identified decreased levels of UMOD protein in CAD. These findings have been confirmed by ELISA. Furthermore, the levels of UMOD were observed as more highly decreased in recent myocardial infarction CAD patients, indicating the importance of this protein as an early diagnostic biomarker. Conclusively, our study represents a non-invasive urinary EVs trove of differentially expressed proteins in CAD. This will form a groundwork for understanding the pathophysiology of CAD and will help in future translational research utilizing uEVs.

Safety and tolerability of long-term apomorphine infusion in advanced Parkinson's disease: an Indian multi-center (APO-IND) experience.

Advanced Parkinson's Disease (APD) is complicated by the emergence of motor and non-motor fluctuations, which are initially predictable and eventually become unpredictable, in part due to erratic gastric absorption and short half of oral levodopa. Attempts to manage such fluctuations with oral dopaminergic drugs often lead to disabling dyskinesias. Continuous Subcutaneous Apomorphine Infusion (CSAI), despite being approved for the treatment of APD since 1993, was approved in India only in 2019. We studied the safety, tolerability and efficacy of CSAI in Indian patients with APD in a registry design to raise local awareness of this important treatment. We conducted a prospective registry-based observational audit at 10 centers across different states of India. Patients with APD, not responding to or with significant side effects from oral dopaminergic therapy, were assessed at baseline and at month 6 and 12 following CSAI infusion. Fifty-one patients completed the study, CSAI significantly reduced the functional impact of dyskinesia (p < 0.01 at 6 months and p < 0.001 at 12 months). There was a significant improvement in the OFF-state from baseline (p < 0.01 at 6 months and p < 0.001 at 12 months) No discernible side effects were observed apart from mild site reaction (n = 7), nausea (n = 7) skin nodules (n = 2). CSAI demonstrated safety, efficacy, tolerability and improved quality of life in patients with APD, as shown in previous studies. Our study highlighted current existing inequalities in treatment availability, lack of awareness, knowledge gap, affordability and cost remains a concern regarding apomorphine use in Indian PD population.

Different Biofluids, Small Extracellular Vesicles or Exosomes: Structural Analysis in Atherosclerotic Cardiovascular Disease Using Electron Microscopy Techniques.

Small extracellular vesicles (sEVs) or exosomes are secretory vesicles largely involved in cell-cell communications and found to play a role in development as well as diseases including atherosclerosis. They hold a huge potential for translational research by devising better clinical diagnostics, biomarker discovery, drug delivery, and therapeutic strategies. Variations terms of morphology and distribution are crucial to biological function integrity. Moreover, it is dependent on susceptibility to influential factors of the environment like cell stress, inflammation, and secretion by different cells in subsequent biofluids. We have observed the morphological variations in sEVs or exosomes freshly isolated from patients with atherosclerotic cardiovascular disease (AsCVD), in blood plasma, saliva, and urine biofluids compared to healthy controls. High-resolution images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) for the characterization of sEVs morphology. Western blotting and immuno-TEM gold labeling confirmed the presence of exosome markers. For the first time, we report size and shape variations, which suggest the existence of different functions of sEVs in the disease state. Morphological variations in sEVs were observed significantly in noninvasive AsCVD saliva and urine samples, important to understand the cell behavior and physiological state. These variations will be useful to investigate their possible role in the disease process.

Neuropalliative Care in India - Barriers, Challenges and Future Directions.

Neuropalliative care is an emerging sub-specialty of neurology and palliative care that aims to relieve suffering from symptoms, reduce distress and improve the quality of life of people with life-limiting neurological conditions and their family caregivers. As advances are being made in the prevention, diagnosis, and treatment of neurological illnesses, there is an increasing need to guide and support patients and their families through complex choices involving immense uncertainty and important life-changing outcomes. The unmet need for palliative care in neurological illnesses is high, especially in a low-resource setting like India. This article discusses the scope of neuropalliative care in India, the barriers and challenges that impede the specialty's development, and the factors that could facilitate the development and scale-up delivery of neuropalliative services. The article also attempts to highlight priority areas for advancing neuropalliative care in India which include context-specific assessment tools, sensitization of the healthcare system, identification of intervention outcomes, the need for developing culturally sensitive models based on home-based or community-based care, evidence-based practices, and development of manpower and training resources.

Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Neurogenic Supine Hypertension and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease.

Background: Natural history and disease progression in patients with Idiopathic Parkinson's Disease (PD) is quite heterogeneous. Autonomic dysfunction occurs commonly among Idiopathic PD patients. Heart rate variability and ambulatory blood pressure monitoring are used to assess cardiac autonomic dysfunction. The prevalence and magnitude of supine hypertension in Indian PD patients has not been studied to date. The present study aimed to record cardiovascular autonomic functions and supine hypertension in PD patients and to correlate them with the age of onset, duration and severity of the disease, and non-motor symptom burden. Material and Methods: The cross-sectional study involved 60 PD patients. Webster rating scale was used to determine the disease severity. Non-motor symptom burden was assessed using the Non-Motor Symptom Scale (NMSS). Ambulatory blood pressure monitoring and heart rate variability parameters determined cardiac autonomic function. Supine hypertension was defined as Systolic Blood Pressure (SBP) ≥150 mmHg and/or DBP ≥90 mmHg. Less than 10% decrease or even increase in blood pressure during the night were classified as non-dippers. Pearson coefficient was used appropriately to establish correlation. P ≤ 0.05 was considered significant. Results: Age of onset was 61.2 ± 8.7 years and duration of disease was 1.7 ± 1.1 years. Mean Webster and non-motor symptom scores were 12.7 ± 4.4 and 15.5 ± 8.0, respectively. About 50 patients (83%) were non-dipper, while 32 (53%) had supine hypertension. Low Frequency oscillations (LF) (r = 0.28), High Frequency oscillations (HF) (r = 0.29), Standard Deviation NN intervals (SDNN) (0.26), and Root Mean Squared Successive Differences of NN intervals (RMSSD) (r = 0.28) correlated significantly with non-motor symptoms scale. LF (r = -0.39), HF (r = -0.43), SDNN (-0.40), RMSSD (r = -0.41), NN50 (r = -0.38), PNN50 (r = -0.42), mean SBP (r = 0.26), and mean DBP (r = 0.33) correlated significantly with disease duration. PNN50 (r = -0.255), mean SBP (r = -0.29), and mean DBP (r = -0.27) correlated significantly with age at onset. Conclusion: Awareness regarding neurogenic supine hypertension is needed as it occurs commonly among Indian PD patients. Heart rate variability (HRV) parameters and ambulatory blood pressure are of significant help in the detection of early cardiovascular autonomic dysfunction and correlate significantly with disease duration and non-motor symptom burden among PD patients.

Multi-Modal Rehabilitation Therapy in Parkinson's Disease and Related Disorders.

Long-term use of dopaminergic therapy in Parkinson's disease (PD) is associated with reduction in efficacy and disabling dyskinesias. The current medical or surgical treatment modalities are ineffective for atypical parkinsonism syndromes. Hence, there is a need for holistic and cost-effective non-pharmacological interventions that act via multiple mechanisms to improve motor as well as non-motor symptoms among PD patients. Rehabilitation strategies focusing on multiple mechanisms can lead to improvement in certain symptoms among PD patients, which may be refractory to medical and surgical therapy. However, there is scanty literature available on the role of various rehabilitation strategies in patients with atypical parkinsonism patients. Multiple rehabilitation strategies such physiotherapy, aerobic exercises, strength/resistance exercises, treadmill training, cueing, dance and music, speech language therapy, occupational therapy, hydrotherapy, and martial arts have been found to improve motor as well as non-motor symptoms among PD patients. Newer modalities such as virtual-reality-based devices, exergaming, wearable sensors, and robotic prosthetic devices may be exciting future prospects in rehabilitation among patients with PD and atypical parkinsonian syndromes. This narrative review assessed and summarized the current evidence regarding the role of various rehabilitation strategies in PD and atypical parkinsonian syndromes. Furthermore, evidence regarding recent advancements in rehabilitation for patients with parkinsonism was highlighted. Despite the beneficial effect of rehabilitation in PD, there is still scanty literature available from India on rehabilitation strategies among PD patients. Larger prospective randomized control trials from India and other low- and middle-income countries, focusing on various rehabilitation strategies among PD patients, are an unmet need.

Efficacy of pranayama in preventing COVID-19 in exposed healthcare professionals: A quasi-randomized clinical trial.

BACKGROUND: The global outbreak of COVID-19 has created a challenging situation, especially for the frontline Health Care Professionals (HCPs), who are routinely exposed and thus are at a higher risk of infection. Pranayama, a component of Yoga, is known to improve immune function and reduce infection. However, no clinical trial on the efficacy of Pranayama in preventing COVID-19 has yet been conducted. AIM AND OBJECTIVE: This quasi-randomized clinical trial assessed the efficacy of Pranayama in preventing COVID-19 infection in HCPs routinely exposed to COVID-19. METHODOLOGY: The study was conducted at 5 different COVID-19 hospitals, India in year 2020. The inclusion criteria were being an HCP exposed to COVID-19 patients and being negative on antibody tests. 280 HCPs were recruited sequential and assigned to intervention and control groups. Of these, 250 HCPs completed the study. The intervention was twice daily practice, for 28 days, of specially designed Pranayama modules under the online supervision of Yoga instructors. The HCPs in the control group were advised to continue their normal daily routine, but no pranayama sessions. Participants who developed symptoms suggestive of COVID-19 were subjected to Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) or Point of Care Rapid Antigen Test (RAT) for confirmation of the diagnosis. All the participants were tested for antibodies to COVID-19 on 28th day of the intervention to detect any asymptomatic infection. RESULTS: The intervention (123) and control (127) groups had comparable demographics and baseline characteristics. At end of 28 days of intervention, nine participants in the control group and one in the intervention group developed COVID-19 (P-value: 0.01, Odds Ratio: 0.107, 95% CI: 0.86; Risk Ratio: 0.11, 95% CI: 0.89). CONCLUSION: The intervention of twice daily practice of the Pranayama module for 28 days in HCPs might have made a noteworthy contribution and may have helped in preventing COVID-19 infection.