Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

Is it atopic asthma, chronic eosinophilic pneumonia, or eosinophilic granulomatosis with polyangiitis?

A 45-year-old man, used to work in a cement factory, presented to us with a history of adult-onset sub-optimally controlled asthma and was initially managed as a case of acute exacerbation of allergic asthma. However, his repeated evaluation revealed raised eosinophil count, raised serum total IgE and persistent chest infiltrates on imaging. He was provisionally managed empirically with a short course of oral steroids and advised follow-up on an out-patient basis to rule out the possibility of idiopathic eosinophilic pulmonary syndromes. The patient was then lost to follow-up, and after four years, he presented with a vasculitic presentation and was diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA). He improved with corticosteroids and cyclophosphamide pulse therapy. This case depicts the importance of evolving nature of EGPA wherein the eosinophilic phase of the disease can mimic other pulmonary eosinophilic diseases and vasculitic symptoms can be delayed as much as by four years.

Utility of ambulatory blood pressure monitoring in detection of masked hypertension and risk of hypertension mediated organ damage in normotensive patients with type 2 diabetes mellitus.

PURPOSE: In patients with diabetes, unrecognised hypertension is a serious problem risk factor for the development and progression of chronic complications. The study aimed to determine the prevalence of masked hypertension in normotensive diabetic patients, the factors affecting it, and its association with diabetes complications using ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: A cross-sectional observational study was conducted on 150 normotensive diabetic patients. Patients were subjected to an interview and clinical examination to record demographic data, epidemiological data, and significant past history. ABPM was performed for each patient. Urine samples, echocardiogram, and ophthalmologic fundoscopy were done to check for diabetes-related complications. RESULTS: The mean age of all participants was 56.7 ± 7.8 years. A total of 93 patients (62%) were males. 99 (66%) patients had masked hypertension. A total of 85 (56.7%) were non-dippers, 49 (32.7%) were dippers, 1 (0.7%) was extreme dipper and 15 (10%) were reverse dippers. Non-dipping and reverse dipping were associated with concentric left ventricular hypertrophy LVH (p < .001). Masked hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.008) whereas, nocturnal hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.003). CONCLUSIONS: A single office blood pressure (BP) reading cannot rule out hypertension in patients with diabetes. Regardless of hypertension, clinicians should have all patients, especially patients with diabetes, undergo ABPM at least once. Masked hypertension, changes in nocturnal dipping and other phenomena that raise the risk of diabetes complications but cannot be measured by office BP can be measured by ABPM, and thus ABPM can provide a good prognostic benefit.

Quantum dynamics of H + LiH reaction and its isotopic variants.

Time-dependent quantum wave packet dynamics study is carried out to investigate the initial state selected channel specific reactivity of H + LiH collisional system on a new and more accurate ab initio potential energy surface developed by Wernli et al. [J. Phys. Chem. A 113, 1121 (2009)]. The H + LiH reaction proceeds through LiH depletion and H-exchange paths. While the former path is highly exoergic (by ∼2.258 eV), the latter path is thermoneutral. State selected and energy resolved integral reaction cross sections and thermal rate constants are reported and compared with the literature data. The reactivity of the LiH depletion channel is found to be greater than the H-exchange channel. Rotational excitation of the reagent LiH molecule causes a decrease of reactivity of both the channels. On the other hand, the vibrational excitation of the reagent LiH decreases the reactivity of the LiH depletion channel and increases the reactivity of the H-exchange channel. The effect of isotopic substitution (H by D) on the reaction dynamics is also examined.

Dynamic vs static external fixation of distal radial fractures: A randomized study.

OBJECTIVES: The present randomized study is conducted to compare the functional and anatomical outcomes of dynamic multiplanar external fixation against that of static external fixation in the management of displaced unstable comminuted fractures of the distal radius. MATERIALS AND METHODS: Sixty adult patients with displaced unstable comminuted fractures of the distal radius were randomly allocated either to the dynamic (n=30) or static (n=30) fixator groups. Patients in the dynamic fixator group were managed with closed reduction and application of Penning-type articulated fixator (Orthofix, Srl, Italy); the injured wrist was partially dynamized at 3 weeks. Patients in the static group were managed with monoplanar static external fixator of Joshi's external stabilizing system (JESS) type fixator. In both groups, the fixator was maintained for 6-8 weeks. The patients were followed-up over 2 years. The primary outcome measures were the functional outcome as measured using the Gartland and Werley and DASH scores and anatomical outcome as measured using the Lindstrom score. The secondary objective was to correlate anatomical and functional outcomes and to look at overall local complications. RESULTS: Palmar tilt was better restored in the Penning fixator group (P<0.0001). There was reduced loss of ulnar tilt (P=0.05) and radial height (P=0.04) in the Penning fixator group. Gartland and Werley score was better in the Penning fixator group at each time point of the follow-up. The DASH score was similar in the two groups at 2 years (P=0.14). There was poor correlation (0.19) between functional outcome and anatomical restoration at 2 years. CONCLUSIONS: In the management of displaced unstable comminuted fracture of the distal radius, use of an articulated multiplanar external fixator, allowing partial dynamization of the injured wrist at 3 weeks, resulted in improved early functional and anatomical outcome as compared to static external fixation. However, there was no significant difference in functional outcome at 2 years.

Operative versus nonoperative management of displaced midshaft clavicle fractures: a prospective cohort study.

OBJECTIVES: To compare results of primary internal fixation of acute displaced midshaft clavicle fractures with those managed nonoperatively in terms of fracture union and functional outcome. DESIGN: Prospective cohort study. SETTING: Level II military trauma center. PATIENTS/PARTICIPANTS: Seventy-three patients (civilian and military) between 20 and 50 years of age with displaced midshaft clavicle fractures were allocated either to the operative (n = 45) or nonoperative (n = 28) group. INTERVENTION: Patients in the nonoperative group were managed by simple sling immobilization, whereas in the operative group, fractures were reduced and fixed with a contoured reconstruction plate. MAIN OUTCOME MEASUREMENTS: The patients were actively followed up during an 18-month period. Primary outcome measures were the rates of nonunion and symptomatic malunion; secondary outcomes included the assessment of the Constant score and the overall local complication rate. RESULTS: The 18-month follow-up rate was 90%. All fractures in the operative group united compared with eight nonunions (29%) in the nonoperative group (P = 0.002). Ten symptomatic malunions (36%) occurred in the nonoperative group, whereas only two (4%) were reported for the operative group (P = 0.0008). Constant shoulder scores were significantly better for the operative group at all follow-ups (P < 0.0001). All six operative complications were implant-related. CONCLUSIONS: In this prospective cohort study, primary open reduction and internal plate fixation of acute displaced midshaft clavicular fractures resulted in improved outcomes and a decreased rate of nonunion and symptomatic malunion compared with nonoperative treatment.