The exploration of Nanozymes for biosensing of pathological states tailored to clinical theranostics.

The nanozymes (NZs) are the artificial catalyst deployed for bio sensing with their uniqueness (high robustness, surface tenability, inexpensive and stability) for obtaining a better response/miniaturization of the varied sensors compared to their traditional ancestors. Now a days, nanomaterials with their broadened scale such as metal-organic frameworks (MOFs), metals/metal oxides are widely engaged in the generation of NZs based biosensors (BS). Diverse strategies like fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), and electrochemical sensing principles were implemented for signal transduction of NZs. Despite of broad advantages, numerous encounters (like specificity, feasibility, stability and issues in scale-up) are affecting the potentialities of NZs based BS, and thus need a prior attention for a promising exploration for a revolutionary outcome in advanced theranostics. This review is included with different types of NZs, the progress of numerous NZs tailored bio-sensing techniques in detection of abundant bio analytes for the theranostic purpose. Further, discussion was highlighted with some recent challenges along with their progressive way of possible overcoming followed by commercial outbreaks.

Microalbuminuria as a Predictor of Early Neurological Deterioration and Poor Functional Outcomes in Acute Ischemic Stroke.

Background Ischemic stroke is a major health crisis with significant consequences. Microalbuminuria, a sign of endothelial dysfunction, has been linked to adverse outcomes in ischemic stroke. Early neurological deterioration (END) is a critical factor influencing the patient's prognosis. This study aimed to determine the prevalence of microalbuminuria, its predictive value in assessing END, and its prognostic implications in acute ischemic stroke (AIS). Methodology This study conducted at Pradyumna Bal Memorial Hospital, Kalinga Institute of Medical Sciences Bhubaneswar (November 2020-April 2022) included 114 AIS patients over 18 years who presented within 24 hours of stroke onset. Demographics, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) scores (admission and day three), modified Rankin scores (day 10), urinary albumin-to-creatinine ratios, and carotid artery Doppler studies were collected. Results The mean age of the patients was 61.87 years, with males constituting 72.8% of the population. Hypertension (50.9%) and diabetes mellitus (28.9%) were the most common comorbid conditions. The mean NIHSS stroke severity at presentation was 11.30. END occurred in 38.6% of patients. Overall, 43.9% of cases showed carotid stenosis, and the mean carotid intimal media thickness was 1.08 mm. Notably, the presence of microalbuminuria significantly increased the chances of both END (39.45 times higher risk) and worse functional outcomes (odds ratio = 19.147, p = 0.001). Conclusions Microalbuminuria emerges as a robust independent predictor of END and a poor prognosis in AIS. These findings highlight the importance of early microalbuminuria identification and intervention to reduce END risk and potentially improve outcomes in AIS patients.

Assessment of Pulmonary Functions in Parkinson's Disease and Unveiling the Role of Levodopa Therapy: A Cross-Sectional Study.

INTRODUCTION: This investigation aimed to thoroughly characterize the range of pulmonary function abnormalities present in individuals with Parkinson's disease (PD) and to evaluate the effects of levodopa therapy on these respiratory dysfunctions. METHODS:  Ninety-five PD patients diagnosed via the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria were recruited, excluding those with a smoking history or unable to perform pulmonary function tests (PFTs). Severity was assessed using the Hoehn and Yahr Scale. Spirometry-measured PFT parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR)) were compared against matched predicted values. The changes in PFT parameters post-levodopa challenge were assessed. RESULTS: Most of the PD patients were aged between 51-60 years, with a mean age of 55.89 ± 8.37 years. Of these, 65.3% were male. A significant proportion of the cohort exhibited restrictive pulmonary patterns (73.7%), while a smaller fraction displayed obstructive (7.4%) or normal (18.9%) pulmonary function patterns. Notably, levodopa treatment correlated with marked improvements in all measured PFT parameters, especially evident in the enhancements from the "off" medication stage to the "on" stage for FVC and FEV1 (P=0.0001). A weak positive correlation between the severity of respiratory restriction and the duration of PD (r = 0.139, P = 0.021) was found, suggesting that PD's progression exerts an increasingly adverse effect on respiratory function over time. CONCLUSION:  The findings of this study illustrate that restrictive pulmonary abnormalities are more prevalent than obstructive patterns in PD patients and that these patients respond favorably to levodopa therapy.

Pathophysiological Mechanisms and Neurological Manifestations in COVID-19.

With increasing knowledge of the coronavirus disease-2019 (COVID-19), we now understand that COVID-19 presents with various extrapulmonary manifestations with multi-organ involvement. Involvement of the central nervous system (CNS) occurs probably via transsynaptic spread or transfer across the blood-brain barrier. Hypoxia, immune-mediated injury, and vascular damage are the potential mechanisms for the CNS manifestations. Headache, dizziness, chemosensory disturbances, such as loss of smell, taste, encephalopathy, stroke, etc., are among the commonly encountered neurological presentations. Headache is identified as one of the red flag symptoms for COVID-19. Sudden onset of loss of smell and/or taste in the absence of nasal congestion can help in COVID-19 case identification and testing prioritization. Both hemorrhagic and ischemic brain injury is common in patients developing stroke. Besides these, COVID-19-associated CNS involvement demands more careful attention toward patients with existing neurological disorders especially that are managed with immunosuppressant agents. In all, neurological involvement in COVID-19 is not uncommon and may precede, occur concomitantly or after the respiratory involvement. It may also be the sole presentation in some of the patients necessitating high vigilance for COVID-19. In this review, we briefly discussed the pathogenesis of CNS involvement and some important neurological manifestations in COVID-19. How to cite this article: Zirpe KG, Dixit S, Kulkarni AP, Sapra H, Kakkar G, Gupta R, et al. Pathophysiological Mechanisms and Neurological Manifestations in COVID-19. Indian J Crit Care Med 2020;24(10):975-980.

Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants.

OBJECTIVE: Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis. MATERIALS AND METHODS: Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls. RESULTS: The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score. CONCLUSION: In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA. KEY POINTS: • Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging. • White matter was more affected than grey matter in early MSA. • Clinical variables did not correlate with early structural changes.