Obturator Nerve Block: An Anatomical Perspective.

Background A comprehensive understanding of the anatomy of the obturator nerve after its emergence from the obturator foramen is essential when undertaking an obturator nerve block effectively. This study was conducted to provide precise anatomical guidance of the obturator nerve block with surface landmarks in the inguinal region. Materials and methods A cross-sectional observational study was carried out on 34 dissected embalmed cadaveric lower limbs to investigate anatomic variability of obturator nerve localization concerning bony/ligamentous landmarks viz. the pubic tubercle, anterior superior iliac spine, inguinal ligament, and femoral artery as well as the adductor longus. Results The pubic tubercle and inguinal ligament were found to be the "least variable indicator" and palpable landmark for localization of the main trunk of the obturator nerve exhibiting lesser standard deviation of the mean distance from the obturator nerve exit. Among the soft tissue (vessel/muscle) parameters, the shortest distance of the adductor longus muscle from the obturator nerve exit was found to have the lowest standard deviation, thus making it the most reliable parameter for obturator nerve localization. Conclusion High anatomic variability in the obturator nerve's localization does exist, and this explains the difficulty frequently encountered in the application of regional anesthetic techniques. The pubic tubercle and inguinal ligament points were found to be the least variable and most reliable landmarks for localization of the main trunk of the obturator nerve.

Diabetic post-covid mucormycosis: A dermatoglyphic prediction.

Aim: To identify the characteristic pattern/parameter among diabetic post-covid mucormycosis patients which may further help in identifying such susceptible patients in a much earlier course of the disease. Materials and Methods: The study was done with 30 diabetic patients (21 males and 9 females) admitted in RIMS Ranchi during the second wave of Covid-19 for post-covid complications. Palm and fingerprint pattern was taken by ink and pad method to measure the qualitative and quantitative parameters. Result: Diabetic post-covid mucormycosis patients were found to have predominantly whorl pattern in males, loop in females, and C-line pattern absent in 36.6%. Proximal axial triradii with ulnar deviation was 76.6%. All the ridge counts (except ab ridge count of right hand) when compared with hypothesized value were found to be significant with P value (<0.005). None of the three angles measured were found to be significant. Conclusion: All the ridge counts (except ab ridge count of right hand) were found to be a reliable parameter for the diagnosis of diabetic post-covid mucormycosis. ATD angle known to be the most reliable parameter for diagnosis of diabetes mellitus in dermatoglyphics is found to be nonreliable with respect to diabetes post-covid mucormycosis.

ATF5 is a regulator of exercise-induced mitochondrial quality control in skeletal muscle.

OBJECTIVES: The Mitochondrial Unfolded Protein Response (UPRmt) is a compartment-specific mitochondrial quality control (MQC) mechanism that uses the transcription factor ATF5 to induce the expression of protective enzymes to restore mitochondrial function. Acute exercise is a stressor that has the potential to temporarily disrupt organellar protein homeostasis, however, the roles of ATF5 and the UPRmt in maintaining basal mitochondrial content, function and exercise-induced MQC mechanisms in skeletal muscle are not known. METHODS: ATF5 KO and WT mice were examined at rest or after a bout of acute endurance exercise. We measured protein content in whole muscle, nuclear, cytosolic and mitochondrial fractions, in addition to mRNA transcript levels in whole muscle. Using isolated mitochondria, we quantified rates of oxygen consumption and ROS emission to observe the effects of the absence of ATF5 on organelle function. RESULTS: ATF5 KO mice exhibited a larger and less functional muscle mitochondrial pool, most likely a culmination of enhanced biogenesis via increased PGC-1α expression, and attenuated mitophagy. The absence of ATF5 resulted in a reduction in antioxidant proteins and increases in mitochondrial ROS emission, cytosolic cytochrome c, and the expression of mitochondrial chaperones. KO muscle also displayed enhanced exercise-induced stress kinase signaling, but a blunted mitophagic and UPRmt gene expression response, complemented by significant increases in the basal mRNA abundance and nuclear localization of ATF4. Instead of promoting its nuclear translocation, acute exercise caused the enrichment of ATF5 in mitochondrial fractions. We also identified PGC-1α as an additional regulator of the basal expression of UPRmt genes. CONCLUSION: The transcription factor ATF5 retains a critical role in the maintenance of mitochondrial homeostasis and the appropriate response of muscle to acute exercise for the optimization of mitochondrial quality control.

Design and synthesis of benzo[d]thiazol-2-yl-methyl-4-(substituted)-piperazine-1-carbothioamide as novel neuronal nitric oxide inhibitors and evaluation of their neuroprotecting effect in 6-OHDA-induced unilateral lesioned rat model of Parkinson's disease.

Neuronal nitric oxide synthase (nNOS) is an enzyme constitutively expressed in the mammalian brain and skeletal muscles. The excessive activation of nNOS in the neurons results in oxidative and nitrosative stress associated with neuronal loss in various neurological disorders. Several nNOS inhibitors have been reported to limit the excessive activation of nNOS. In the present work, we have designed and carried the synthesis of benzo[d]thiazol-2-yl-methyl-4-(substituted)-piperazine-1-carbothioamide as novel neuronal nitric oxide inhibitors (5-28, twenty-four compounds). Stably transfected HEK 293 cells expressing NOS isoforms treated with the compounds (5-28) showed that the eight compounds exhibited > 95% cell survival in the MTT assay. nNOS inhibition assay of the eight compounds illustrated that the compound 18 was most selective for nNOS (nNOS=66.73 ± 1.51; eNOS=28.70 ± 1.39; iNOS =13.26 ± 1.01) in HEK 293 cells expressing NOS isoforms. 6-OHDA-induced unilaterally lesioned rats treated with the compound 18 showed the improvement in motor and non-motor functions. Furthermore, the compound 18 showed the increased levels of dopamine and decreased levels of glutamate and nitrite ions in the isolated rat brain. In the docking analysis, the compound 18 showed the significant binding affinity with the nNOS binding site (the ∆G value = - 9.0 kcal/mol). Overall results demonstrated that the N-(benzo[d]thiazol-2-ylmethyl)-4-(4-nitrophenyl) piperazine-1-carbothioamide (the compound 18) possessed significant nNOS inhibiting activity and neuroprotecting potential in 6-OHDA-induced unilaterally lesioned rat model of PD and more work will be required to establish the role of the compound 18 in the therapy of PD and other neurodegenerative disorders.

The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle.

BACKGROUND: Aging decreases skeletal muscle mass and quality. Maintenance of healthy muscle is regulated by a balance between protein and organellar synthesis and their degradation. The autophagy-lysosome system is responsible for the selective degradation of protein aggregates and organelles, such as mitochondria (i.e., mitophagy). Little data exist on the independent and combined influence of age, biological sex, and exercise on the autophagy system and lysosome biogenesis. The purpose of this study was to characterize sex differences in autophagy and lysosome biogenesis in young and aged muscle and to determine if acute exercise influences these processes. METHODS: Young (4-6 months) and aged (22-24 months) male and female mice were assigned to a sedentary or an acute exercise group. Mitochondrial content, the autophagy-lysosome system, and mitophagy were measured via protein analysis. A TFEB-promoter-construct was utilized to examine Tfeb transcription, and nuclear-cytosolic fractions allowed us to examine TFEB localization in sedentary and exercised muscle with age and sex. RESULTS: Our results indicate that female mice, both young and old, had more mitochondrial protein than age-matched males. However, mitochondria in the muscle of females had a reduced respiratory capacity. Mitochondrial content was only reduced with age in the male cohort. Young female mice had a greater abundance of autophagy, mitophagy, and lysosome proteins than young males; however, increases were evident with age irrespective of sex. Young sedentary female mice had indices of greater autophagosomal turnover than male counterparts. Exhaustive exercise was able to stimulate autophagic clearance solely in young male mice. Similarly, nuclear TFEB protein was enhanced to a greater extent in young male, compared to young female mice following exercise, but no changes were observed in aged mice. Finally, TFEB-promoter activity was upregulated following exercise in both young and aged muscle. CONCLUSIONS: The present study demonstrates that biological sex influences mitochondrial homeostasis, the autophagy-lysosome system, and mitophagy in skeletal muscle with age. Furthermore, our data suggest that young male mice have a more profound ability to activate these processes with exercise than in the other groups. Ultimately, this may contribute to a greater remodeling of muscle in response to exercise training in males.

A reliable fluorimetric method to screen the nitric oxide synthase inhibitors in 96 well plate.

In general, 4 amino-5-methylamino-2',7'-difluorescein diacetate (DAF-FM-DA) dye is used to detect nitric oxide in biological systems through cell imaging. In this study, we have used 96 well plate format to quantify nitric oxide using DAF-FM-DA through a multimode reader (or independently using fluorospectrometer) and could be visualized in a fluorescence microscope. Similar study otherwise will require a high-end instrument. The method has been validated to screen NOS inhibitors in the HEK 293T cell lines over-expressing the NOS isoforms. We observed that the method is very simple to use, adaptive, sensitive and most importantly it saves time. REAGENTS/TOOLS: Ethanol (70% [v/v] in distilled water), Nω-Nitro-l-arginine (l-NAME), 7-Nitro-Indazole (7-NI) (Sigma, St. Louis, MO), HEK 293T cell lines (National Centre for Cell Science (NCCS), Pune, India), DMEM (Himedia laboratories Pvt), Fetal Bovine Serum (FBS) (Invitrogen, Carlsbad, CA), 100 U/mL penicillin, and 0.1 mg/mL streptomycin in a 5% CO2 atmosphere. Hank's Balanced Salt Solution (HBSS) without Phenol Red of pH 7.4 was prepared with the following composition: NaCl, 8.0g, KCl, 0.4g, CaCl2, 0.14g, MgSO4⋅7H2O, 0.1g, MgCl2·6H2O, 0.1g, Na2HPO4·2H2O, 0.06g, KH2PO4, 0.06g, glucose, 1.0g, NaHCO3, 0.35g, H2O, to 1000 ml, Sterilized and refrigerated, Calcium Ionophore A23187 (Sigma Aldrich 52665-69-7) DAF-FM Di Acetate (Molecular Probes Life Technologies), and DAF-FM Di Aceatate was prepared as a stock solution (5 mM) in DMSO, divided into aliquots and stored at -20 °C, followed by dilution to the required concentration in HBSS buffer before use. EQUIPMENT: Neubauer chamber, Microtube centrifuges (1.5 mL), Micropipettors,10,100, and 1000 mL with corresponding tips, multimode reader (Tecan, Synergy-HT), inverted fluorescence microscope (Nikon, eclipse Ti-S), black flat bottom Microplates (96-well) (Corning 3603).

Impact of health education based intervention on community's awareness of dengue and its prevention in Delhi, India.

Dengue is endemic in India. The capital, Delhi, continues to witness a higher number of cases due to urbanization-related factors. This study is intended to implement health education towards prevention of dengue, and to assess its impact on people's knowledge and practices related to causes and prevention of dengue among urban poor in Delhi. Pre- ( n = 484) and post- ( n = 496) intervention surveys from 15 sub-clusters from five slums/slum-like settlements in Delhi were carried out. Health education based intervention was carried out through partnership with the municipal bodies and non-governmental organizations. Socio-demographic characteristics of participants were similar in both surveys. Intervention resulted in significant increase in knowledge on cause, symptom perception and mosquito behaviour in terms of breeding and biting habits. Practice of personal protection measures increased significantly. The participation of people increased during intervention compared to the routine programme. Health education based interventions are instrumental in improving people's knowledge and behaviour. Hence, routine health educational activities as a supportive strategy in the health system need to be strengthened. New integrated approaches such as eco-bio-social approaches with community participation are to be developed and tested in endemic settings like Delhi.

Neuroprotective effect of IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo [4,5-d]pyrimidin-6(7H)-yl)urea) in 6-OHDA induced rodent model of hemiparkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Levodopa (l-DOPA) is the most effective therapy for PD, however, PD progression continues with significant side effects in long term, thus necessitating the search for effective therapy that impedes PD progression. PD therapy through non-dopaminergic pathways offers treatment without the risk of extrapyramidal effects. In this regard, earlier, we had reported, a novel compound IDPU with potential adenosine A2A receptor antagonist effect in haloperidol (chronic treatment) induced Parkinson model. In the present study, we extended our investigation towards i) evaluation of IDPU in well-established 6-OHDA induced Parkinson rat model to establish its role in the therapy of PD ii) its function in alleviating the neuronal loss. We carried the IDPU administration (i.p.) in rats for two weeks after establishing 6-OHDA induced unilateral lesions. The behavioral activity, neurochemical alteration, oxidative stress marker and tyrosine hydroxylase positive neurons in substantia nigra were analyzed. The results showed that IDPU significantly reduced motor and non-motor deficits induced by 6-OHDA in the behavioral tasks such as apomorphine, rota rod and force swim test. Furthermore, the results of oxidative stress biomarkers revealed that IDPU successfully modulated oxidative stress associated biomarkers such as MDA, catalase, superoxide dismutase, nitric oxide and reduced glutathione level. Additionally, IDPU significantly elevated intracellular dopamine, decreased glutamate and calcium levels in brain as compared to 6-OHDA alone treated animals which is evocative of its neuroprotective behavior. Thus, the investigations clearly validated IDPU as a potent anti-parkinsonian agent which showed immense capability to protect neurodegeneration.

Post-lesion administration of 7-NI attenuated motor and non-motor deficits in 6-OHDA induced bilaterally lesioned female rat model of Parkinson's disease.

The preoperative neuroprotective effect of the 7-nitroindazole (7-NI) in 6-hydroxydopamine (6-OHDA) induced unilateral male animal models of Parkinson's disease (PD) has been widely reported. However, the therapeutic approach to PD pathology would be closely associated with the post-lesion treatment by 7-NI in 6-OHDA-induced bilateral model. Also, there is a scarcity of data on neuroprotective effect of 7-NI in PD in females. We have studied the neuroprotective effects of 7-NI in 6-OHDA-induced bilaterally lesioned female rats after short-term post-lesion treatment. Sprague-Dawley female rats with bilateral intraventricular injection of either 6-OHDA (10.5µg) (n=8-11/group) or saline (sham; n=8/group) at substantia nigra (SN) were provided with 7-NI (30mg/kg/day) intraperitoneal, once a day during the 3 consecutive days of short term treatment. 6-OHDA lesioned animals developed the motor and non-motor deficits, which were evaluated by behavioral and neuro-biochemical tests from the substantia nigra. Post-lesion administration of 7-NI reduced the motor deficits induced by 6-OHDA in the behavioral tasks such as Rota rod, open field test and forced swim test. Simultaneously, the dopamine levels were restored by 7-NI in post lesion animals up to 76% in comparison to 6-OHDA lesioned animals (23%). Furthermore, antioxidant-like effect of 7-NI was observed in lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione tests. Conclusively, the present study showed that early postoperative administration of 7-NI attenuates the motor deficits induced by 6-OHDA in bilaterally lesioned female rat model of PD.

Migration and access to maternal healthcare: determinants of adequate antenatal care and institutional delivery among socio-economically disadvantaged migrants in Delhi, India.

OBJECTIVE: To identify the determinants of adequate antenatal care (ANC) utilisation and institutional deliveries among socio-economically disadvantaged migrants living in Delhi, India. METHODS: In a cross-sectional survey, 809 rural-urban migrant mothers with a child aged below 2 years were interviewed with a pretested questionnaire. Data on receiving antenatal, delivery and post-natal services, migration history and other social, demographic and income were collected. RESULTS: Recent migrants used the services significantly less than settled migrants. ANC was adequate only among 37% (35% of recent migrant women and 39% of settled migrants). Multinomial regression revealed that being a recent migrant, multiparous, illiterate and married to an unskilled worker were significant risk factors for receiving inadequate ANC. Around 53% of deliveries took place at home. ANC seeking has a strong influence on place of delivery: 70% of births to women who received inadequate ANC were at home. Women who are educated, had their first delivery after the age of 20 years and received adequate ANC were more likely to deliver their child in hospital. Post-natal care is grossly neglected among these groups. CONCLUSION: Migrant women, particularly recent migrants, are at the risk of not receiving adequate maternal healthcare. Because migration is a continuing phenomenon, measures to mitigate disadvantage due to migration need to be taken in the healthcare system.

Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury.

The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.

Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats.

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.

Migration and immunization: determinants of childhood immunization uptake among socioeconomically disadvantaged migrants in Delhi, India.

OBJECTIVE: To determine the coverage of childhood immunization appropriate for age among socioeconomically disadvantaged rural-urban migrants living in Delhi and to identify the determinants of full immunization uptake among these migrant children. METHODS: This is a cross-sectional survey of 746 rural-urban migrant mothers with a child aged up to 2 years, who were interviewed with a pretested questionnaire. Data pertaining to the reception of various vaccines, migration history and some other social, demographic and income details were collected. Multiple logistic regression analyses were performed to identify the determinants of full immunization status. RESULTS: Immunization coverage rates were lower among migrants than the general population of Delhi and even lower among recent migrants. The likelihood of a child receiving full immunization rose with age of the mother, her educational attainment and the frequency of her use of health care. The head of household having a secured salaried job also significantly increased the likelihood of full immunization, as did post-natal visits by a health worker. CONCLUSION: Migrant status favours low immunization uptake particularly in the vulnerability context of alienation and livelihood insecurity. Services must be delivered with a focus on recent migrants; investments are needed in education, socio-economic development and secure livelihoods to improve and sustain equitable health care services.

In silico study of naphtha [1, 2-d] thiazol-2-amine with adenosine A 2A receptor and its role in antagonism of haloperidol-induced motor impairments in mice.

Loss of dopaminergic nigrostriatal neurons in the substantia nigra leads to Parkinson's disease (PD). Adenosine A(2A) receptors (A(2A)Rs) have been anticipated as novel therapeutic target for PD. A(2A)Rs potentiate locomotor behavior and are predominantly expressed in striatum. Naphtha [1, 2-d] thiazol-2-amine (NATA), a tricyclic thiazole have been studied as new anti-Parkinsonian compound. AutoDock analysis and pharmacophore study of NATA with known A(2A)R antagonists explicit its efficacy as a possible adenosine receptor antagonist. In vivo pharmacology of NATA showed reduction of haloperidol (HAL)-induced motor impairments in Swiss albino male mice. Relatively elevated levels of dopamine in NATA pre-treated mice are suggestive of its possible role as neuromodulator in PD.