Critical study of Haritakyadi Yoga in Mutrakricchra (Urinary Tract Infection) - A Review

Urinary tract infections (UTI), the second most common type of infection. It is one of the most serious health problem affecting millions of people each year. UTI have been considered a risk factor for the development of end stage renal diseases in children. It is of greatest concern as recurrent infection of UTI can threat to the normal course of growth and development of children. The term Mutrakricchra comes under the disorders of Mutravaha Strotas. ‘Dukhen mutra pravritti’ (Difficulty while micturition-disurea) is cardinal symptom of Mutrakricchra vyadhi. Due to nidana sevana, doshas gets vitiated by their own causes and they enters in basti (Urinary bladder) and produce srotorodha, sankocha and kshobha at mutra marga which further causes Basti pradesh shotha and produce pain and difficulty while passing urine. Ayurveda has significant remedy in the management of Mutrakricchra. Haritakyadi yoga is one of the Ayurvedic formulation used in treatment of Mutrakricchra by means of Shamana chikitsa. Conclusion: Effect of ‘Haritakyadi Yoga’ was seems to be significant in reducing symptoms of Mutrakricchra as well as decreases possibility of drug resistance and recurrence of UTI.

Mitochondrial Retinopathies

The retina is an exquisite target for defects of oxidative phosphorylation (OXPHOS) associated with mitochondrial impairment. Retinal involvement occurs in two ways, retinal dystrophy (retinitis pigmentosa) and subacute or chronic optic atrophy, which are the most common clinical entities. Both can present as isolated or virtually exclusive conditions, or as part of more complex, frequently multisystem syndromes. In most cases, mutations of mtDNA have been found in association with mitochondrial retinopathy. The main genetic abnormalities of mtDNA include mutations associated with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) sometimes with earlier onset and increased severity (maternally inherited Leigh syndrome, MILS), single large-scale deletions determining Kearns–Sayre syndrome (KSS, of which retinal dystrophy is a cardinal symptom), and mutations, particularly in mtDNA-encoded ND genes, associated with Leber hereditary optic neuropathy (LHON). However, mutations in nuclear genes can also cause mitochondrial retinopathy, including autosomal recessive phenocopies of LHON, and slowly progressive optic atrophy caused by dominant or, more rarely, recessive, mutations in the fusion/mitochondrial shaping protein OPA1, encoded by a nuclear gene on chromosome 3q29.

Integrated Proteomic and Metabolomic Analyses of the Mitochondrial Neurodegenerative Disease MELAS

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory Complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of Complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid β-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.

Examining the Impact of Excessive Daytime Sleepiness on Utility Scores in Patients with Obstructive Sleep Apnoea and/or Narcolepsy in Five European Countries

Background: Excessive daytime sleepiness (EDS) is a cardinal symptom of narcolepsy and affects many patients with obstructive sleep apnoea (OSA). EDS is associated with reduced quality of life, increased accident risk, and poor workplace performance. Given the impact of EDS, the ability to predict health-related utility from sleepiness is valuable for examining the cost effectiveness of novel treatments. The aim of this study was to examine the association between EDS and EQ-5D in patients with OSA and/or narcolepsy by modelling EQ-5D utility scores from Epworth Sleepiness Scale (ESS) scores.Methods: Data were obtained from the Europe 2016/2017 National Health and Wellness Survey, an online, general population survey, designed to represent the age and gender composition of each country’s adult population. Analyses included 2,348 patients self-reporting symptomatic and diagnosed OSA (n=2,277), narcolepsy (n=48), or both (n=23). Multivariable models were used to examine ESS as a predictor of EQ-5D utility while adjusting for covariates of interest. Results were validated following the National Institute for Health and Care Excellence Decision Support Unit guidelines for predictive modeling.Results: Utility decreased as EDS severity increased (no EDS: 0.711±0.251, mild: 0.685±0.261, moderate: 0.643±0.268, severe: 0.559±0.323). Whereas participants with only OSA or only narcolepsy did not differ in utility, those with both conditions had lower scores (0.685±0.266 and 0.627±0.325 vs. 0.439±0.340, respectively). Piecewise linear regression identified a single breakpoint at ESS score of 11.29. In the final model, for each point increase in ESS score, the corresponding decrease in EQ-5D utility was larger among patients with ESS scores ≥12 compared to patients with ESS scores ≤11 (model slopes: -0.0131 vs. -0.0026, respectively). Findings from the validation sample confirmed these results.Conclusions: This study demonstrates the impact of sleepiness on quality of life (QoL) and its negative impact irrespective of sleep condition (OSA or narcolepsy). The breakpoint identified is relatively consistent with the established ESS cutoff score ≥11, which demarcates pathological sleepiness. Furthermore, as EDS severity worsens (increases) on the ESS, the impact on QoL is greater.

Questioning the early events leading to the COVID-19 pandemic

Sixteen months after the January 30, 2020 declaration by the World Health Organization of a Public Health Emergency of International Concern regarding the spread of COVID-19, SARS-CoV-2 had infected ~ 170 million humans worldwide of which > 3.5 million had died. We critically examine information on the virus origin, when and where the first human cases occurred, and point to differences between Chinese and later clinical presentations. The official patient Zero was hospitalized in Wuhan, Hubei province, China, on December 8, 2019, but retrospective analyses demonstrate prior viral circulation. Coronaviruses are present in mammals and birds, but whether a wild animal (e.g. bat, pangolin) was the source of the human pandemic remains disputed. We present two contamination models, the spillover versus the circulation model; the latter brings some interesting hypotheses about previous SARS-CoV-2 virus circulation in the human population. The age distribution of hospitalized COVID-19 patients at the start of the epidemic differed between China and the USA–EU; Chinese hospitalized patients were notably younger. The first Chinese publications did not describe anosmia-dysgeusia, a cardinal symptom of COVID-19 in Europe and USA. The prominent endothelial involvement linked with thrombotic complications was discovered later. These clinical discrepancies might suggest an evolution of the virus.

Safety and Tolerability of a Wearable, Vibrotactile Stimulation Device for Parkinson’s Disease

Background: Resting tremor is a cardinal symptom of Parkinson’s disease (PD) that contributes to the physical, emotional, and economic burden of the disease.Objective: The goal of this study was to investigate the safety, tolerability, and preliminary effectiveness of a novel wearable vibrotactile stimulation device on resting tremor in individuals with PD.Methods: Using a randomized cross-over design, subjects received two different vibrotactile stimulation paradigms (high amplitude patterned and low amplitude continuous) on two separate laboratory visits. On each visit, resting tremor was video recorded for 10 min at baseline and while the vibrotactile stimulation was applied. Tremor severity was scored by a blinded clinician.Results: Both vibration paradigms were well safe and well tolerated and resulted in a reduction in resting tremor severity with a moderate effect size (n = 44, p < 0.001, r = 0.37–0.54). There was no significant difference between the two vibration paradigms (p = 0.14).Conclusion: Short durations of vibrotactile stimulation delivered via wearable devices were safe and well tolerated and may attenuate resting tremor severity in individuals with PD. The sample size as well as the potential preliminary effectiveness revealed by two arms of the study could not eliminate the potential for a placebo effect.

Symptom Frequencies and Correlations with Temperature Variations in Suspected Cases of Neuroleptic Malignant Syndrome (NMS)

Background: The incidence of NMS is rare. Relative frequencies of symptoms that are most valuable in making a diagnosis of NMS can be assessed statistically only if a large sample of suspected NMS cases is available. Similarly, the relationship of such NMS symptoms to temperature (a cardinal symptom of NMS) can be meaningfully evaluated only by studying large samples. Method: De-identified archival data on 212 suspected NMS cases were obtained from professionals across the USA and Canada or were extracted from studies published in medical journals. We recorded the symptoms frequencies. The patients’ temperature ranged from 37.20C to 43.00C, with the mean at 39.50 (SD=1.3). All cases were caused by older first-generation antipsychotics (FGAs). We evaluated the frequencies of symptoms reported in these cases. These included symptoms in the realm of mental status, rigidity, and autonomic symptoms. We calculated the frequency of abnormal blood pressure, respiration and heart rate, symptoms such as Dysarthria, Dysphagia, Rigidity, Focal Dystonia, Waxy Flexibility, Myoclonus, Masked Facies, Bradykinesia, Akinesia, Cogwheeling, Stupor, Coma, Obtundation, Mutism, Decrease in Consciousness, Disorientation, Diaphoresis, Sialorrhea, and Seizures. We also calculated their correlations with temperature elevations, the most spectacular symptom of this dangerous syndrome. Results: The highest symptom frequencies (those > 10%) were found for Rigidity (91.0% of patients), Autonomic Instability (66.5%), Diaphoresis (45.8%), Mutism (34.4%), Tremor (31.6%), Stupor (20.3%), Confusion (15.6%), Incontinence (15.6%), Sialorrhea (14.6%), Coma (13.2%), and Dysphagia (11.3%). Other symptoms were too rare within the sample of the 212 suspected NMS cases to calculate the statistical significances of their relationships to temperature. The only significant correlations found of temperature were to increased heart rate and to the severe cases of coma. Discussion and Conclusion: Besides the elevated temperature, the most frequently reported symptoms in this sample of suspected NMS caused by FGAs were Rigidity, Autonomic Instability, Diaphoresis, Mutism, and Tremor. Higher temperature was associated with tachycardia as well as profound impairment of consciousness or coma. Reviews and database studies of second generation antipsychotics (SGAs), also referred to as atypical antipsychotics, suggest a lower incidence of NMS and milder severity of symptoms such as hyperthermia and rigidity. It would be of clinical interest to generate similar de-identified files of archival data for suspected cases of NMS in patients treated with SGAs. Furthermore, a similar profile derived from archival data on milder or prodromal NMS cases could enhance our understanding of this syndrome from a spectrum perspective.

Re-Print Cell Impact: Pathophysiological Mechanism of Sars-Cov-2 in the Olfactory and Gustatory System

Smell and taste alterations are very common in patients with COVID 19, even when we are in an asymptomatic phase of the disease, it is reported that up to 80 to 90% of patients present anosmia and ageusia as a cardinal symptom of the disease. In this manuscript we will mention the alterations and the mode of action of the Sars-cov-2 virus at the level of the nasal and buccal fossae, taking into account the alterations at the cellular level as a result of this, based on current evidence, remembering that it is still unknown. A lot about this disease and the way this virus works.

Headache Characteristics in the Neurological Emergency Department: A Retrospective Study

Background: The care of patients with headache in the emergency department (ED) represents a diagnostic and clinical challenge. Data on the prevalence and characteristics of headache patients in purely neurological EDs are sparse. The aim of the present study is to examine patient profiles with the cardinal symptom of headache in an academic neurological ED, to analyze correlations between headache characteristics and search for differences compared to the interdisciplinary ED.Methods: This retrospective cross-sectional study assessed all patients who presented to the ED of the Department of Neurology at Rostock University Medical Center between November 2013 and November 2016 with the main symptom of headache. Epidemiological, clinical, diagnostic data as well as key data regarding the care structure were recorded. Correlations between headache characteristics and diagnosis at discharge were analyzed and risk profiles were identified using binary logistic regression analysis.Conclusion: This study comprehensively characterized a large collective of patients with the cardinal symptom of headache presenting to a purely neurology emergency department.

Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine – Section on Maternal Disorders

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.