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Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Although regulatory authorities presently authorize extremely few drugs for dealing with multifactorial conditions and conditions of cognition such as Alzheimer's, specific plant-derived agents, consisting of, for instance, galantamine and rivastigmine (a semi-synthetic derivative of physostigmine) finding an application in contemporary medicine. However, in Ayurveda, the Indian traditional system of medicine which is more than 5000 years of ages, selected plants have long been categorized as 'Medhyarasayanas,' from the Sanskrit words 'Medhya,' indicating intellect or cognition, and 'Rasayana,' implying 'rejuvenation.' These plants are utilized both in natural and traditional medicine and offer advantages that pharmaceutical drugs do not have. The article is an attempt to examine the most critical medical plants, consisting of Vacha (Acorus calamus), Ashwagandha (Withania somnifera), Vidhara (Argyreia Nervosa), Shankhapushpi (Convolvulus prostratus), Shatavari (Asparagus racemosus), Mandukaparni (Centella Asiatica), Brahmi (Bacopa monnieri), Jyotishmati (Celastrus paniculatus) which are extensively used for their reputed effectiveness in C.N.S. conditions. This paper’s main aim is to explore C.N.S. Protective drugs or Medhya Rasayana mentioned in Ayurvedic classical textbooks concerning modern science mode of actions and to study the mechanism of the C.N.S. protective drugs. The source for this study is collected from classical Ayurvedic books and commentaries, modern medical science textbooks, and different articles from Pubmed, D.H.A.R.A., Google Scholar, etc. Various Medhya Rasayana mentioned in Ayurvedic texts have potent qualities to enhance memory and relieve medical illnesses related to C.N.S., whether it is related to mental or sensory problems. So, various safe and natural remedies are available in Ayurveda; long-term or short-term mental health can be recovered without any life-threatening complication.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that is estimated to affect 5% of children and adolescents worldwide. The core manifestations of ADHD include impulsivity, inattentiveness and hyperactivity, with there being a high proportion of individuals also experiencing other psychiatric co-morbidities. Currently available treatments for ADHD are limited by the low adherence rates related to adverse events. However, it has been suggested that cannabis-based medicinal products (CBMPs) may be effective in the treatment of ADHD, as evidence has shown how cannabis can lead to improvements in symptoms of hyperactivity and impulsivity. However, there is still limited published data supporting its use and further randomised controlled trials are required to help establish the efficacy, safety and exact role of CBMPs for the treatment of ADHD. ADHD patients can be assessed for receiving potential treatment with CBMPs by specialist clinics, such as Sapphire Medical Clinics, in instances where they have failed to respond to their treatment.

The global burden of non-communicable diseases is increasing rapidly, and adopting a healthy lifestyle is an important strategy to combat it. Ayurveda can play an essential role in this regard, as the main aim of Ayurveda is to prevent diseases by following a healthy lifestyle. However, to implement such traditional knowledge (that is based on a healthy lifestyle). Principles of Ayurveda) in actual practice, a systematic process should be followed. Ayurveda is a traditional system of medicine that applies holistic principles that primarily focus on personal health. Ayurveda originated in India and is one of the oldest healthcare traditions. Ayurveda is often known as the "science of life" because "Ayu" in Sanskrit means life, and "Veda" means science or knowledge. Vagbhatt's Ashtanga Haridyama, Charaka Samhita, Sushruta Samhita (400 BC - 200 AD) and Ashtanga Hrudayam contain detailed descriptions of over 700 herbs and 6,000 sutras. This systematic process must involve serious research (i.e., development and evaluation). Ayurvedic-based lifestyle interventions) and behavioural change. This article explains the importance of Panchakarma therapies or procedures mentioned in Ayurvedic classical textbooks and their implementations to counter Non- Communicable Diseases. As a result, there is a greater goal to accomplish. Traditional knowledge of Ayurveda is found in actual practice that is useful for society. The aim is to explore and seek solutions or treatment options available in Ayurvedic classical texts for Non-Communicable diseases. The source for this study is collected from classical Ayurvedic books and commentaries, modern medical science textbooks and different articles from Pubmed, DHARA, GoogleScholar etc. Exploration of various Panchakarma procedures or therapies described in Ayurvedic classical texts helps us better understand pathologies of Non- Communicable diseases from their root causes and allow us to understand how potent Panchakarma therapies have a healthy influence to counter Non- Communicable diseases.

Background: Breast cancer is the second leading cause of solid tumor brain metastasis. Up to 16% of patients with metastatic breast cancer (mBC), and 50% patients with HER2+ metastatic breast cancer will develop central nervous system (CNS) metastasis overtime. Prognosis in these patients is dismal with a median overall survival of 2-15 months. Despite advances in systemic therapy of mBC, treatment options for patients with breast cancer brain metastasis (BCBM) remain limited. Although newer approaches to treat BCBM are imminently needed, BCBM patients have traditionally been excluded from clinical trials. We aimed to examine the current state of BCBM-related enrollment in ongoing prospective systemic therapy clinical trials for mBC. Methods: We performed a systematic search of the clinicaltrials.gov website on May 1, 2022 to characterize current trends in clinical trial enrollment for BCBM patients in ongoing interventional trials using the key search term “Breast Cancer”. Trial search was further limited to “open” and “interventional studies”. Data was abstracted and verified by two independent researchers. Trials were excluded if they were specific for other disease types, did not include a systemic anticancer pharmaceutical, or excluded advanced/metastatic disease. Inclusion of active CNS disease [BCMB and leptomeningeal disease (LMD)] and exclusion of CNS disease were the co-primary end points. Covariates of interest were gender, location (US, international or both), disease site (breast cancer specific vs multi-disease trials), therapy category (immunotherapy (IO), targeted therapy, endocrine therapy, chemotherapy, or combination) and sponsor type. Logistic regression was used to model inclusion of active CNS disease. Results: A total of 1720 trials were identified, and 576 trials met the inclusion criteria. 179 (31.6%) were phase I, 129 (22.4%) were phase I/II, 196 (34.0%) were phase II, 60 (10.4%) were phase III and 9 (1.6%) were phase IV. 347 (60.4%) were breast cancer specific and 229 (39.6%) were multi-site trials. 66 (11.5%) trials were specific for HER-2+ cancer and 70 (12.1%) were triple negative breast cancer specific. 238 (41.3%) trials were US only and 290 (50.3%) were pharmaceutical industry sponsored. Overall, only 29 trials (5%) included patients with any form of BCBM and only 11 trials (1.9%) allowed patients with LMD. 12 (2.1%) trials allowed patients with treated BCBMs only. In univariate models, breast cancer only trials (OR 4.07, 95% CI 1.77-9.36, p= 0.0009), trials excluding men (OR 1.97, 95% CI 1.03-3.77, p=0.0412), non-IO therapy trials (non-IO vs IO OR 3.57, 95% CI 1.08-11.82, p=0.369), and non-pharmaceutical industry sponsored trials (OR 2.65, 95% CI 1.34-5.22, p =0.0049) were more likely to include patients with active CNS disease. Additionally, inclusion of LMD (OR 7.85, 95% CI 2.19-28.17, p = 0.0016) was a significant predictor of inclusion of active CNS disease. In a combined model, disease site remained significant (breast only vs multi-site OR 4.07, 95% CI 1.77-9.36, p = 0.0009). Conclusion: The vast majority of the ongoing breast cancer clinical trials continue to exclude patients with breast cancer brain metastasis. With an increasing prevalence of breast cancer brain metastasis, evaluating intracranial efficacy of novel therapies early on in drug development remains an area of urgent unmet need. Citation Format: Omar Elghawy, Walter Banfield, John Wang, Bethany Horton, Varinder Kaur. Enrollment Trends Among Patients With Breast Central Nervous System Metastasis in Active Clinical Trials [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-01.

Therapeutic phlebotomy allows for a controlled and gradual decrease in red cell mass leading to improved blood flow and symptomatic relief in polycythaemia. The present study was aimed to determine the impact of serial fixed volume and fixed interval therapeutic phlebotomy protocol on the laboratory and clinical parameters in patients of polycythaemia.This prospective longitudinal study was conducted over 18 months. The desired haematocrit for polycythemia vera and secondary polycythemia was 45% and 52% respectively. A fixed volume of 350 ml phlebotomy was performed every-three days till the achievement of desired haematocrit. Complete blood count was performed before and after each procedure and iron studies were done at the time of enrolment and after the achievement of desired haematocrit. Post-procedure symptomatic relief was assessed by a 10-point visual analogue scale (VAS).Of the 29 patients enrolled in the study, 3 patients were lost to follow up and data of 26 patients was analyzed. Mean Hb declined from 17.84 ± 1.88 gdLOur protocol yielded rapid and marked improvement in patients of primary and secondary polycythemia with minimal adverse events and significant amelioration of clinical parameters.

For many heart failure patients, a heart transplant is required. Few hospitals in Canada perform heart transplants; thus, patients and caregivers must relocate to access transplant care.This study explores Canadian patients' and caregivers' experiences of to access transplant care and how patients and caregivers define home. The study's goal is to gain insights from the patient and caregiver experience and identify opportunities to improve the experience for those who relocate to access heart transplants. The research question was: How is the concept of home connected to the heart transplant journey?We conducted 18 interviews with advanced heart failure patients and caregivers, to explore patient and caregiver experiences of relocating to access transplant care. Patients and caregivers ranged in ages from 20's to 60's and had left their home of origin to move to a new location where medical care was available. 7 patients were male, 3 were female. All caregivers were female.Patients and caregivers identified three supports during relocation: other patients and caregivers, medical team and family. Patients and caregivers defined home as friends, family, community, warmth, safety, belonging and comfort.During relocation, patients and caregivers were supported by: other patients and caregivers, their medical team and family, and how these people made them feel: safe, warm, comfortable and that they belonged is how they defined home. The supports and definitions of home are connected; thus, a sense of home is inextricably linked to the transplant journey for patients and caregivers.

Schematic illustration of the synthesis of topologically modified ZnS NPs and their in vitro effects on a fungal pathogen, mechanistic electrostatic interactions and seed treatment for the uptake of Zn in rice seedlings.

Campanula dimorphantha Schweinf. is documented first time from Doaba region of Punjab, India. This study will be useful for Botanists, taxonomists, researchers etc. for identification of species.

Background: Contact screening was conducted under ICMR (REFERENCE ID: 2019-07811) programme in villages near SGT hospital, Gurugram. Objective: To evaluate risk factors, extent of spread of tuberculosis among household contacts of tuberculosis cases and to create awareness. Methods and Material: Address of TB cases were taken from RNTCP register at DOTS clinic, SGT medical college. Then all household contacts of positive cases were screened, counselled and advised to approach ASHA Workers if such symptoms appear. Data was analysed using appropriate statistical methods. Results:21 Index cases along with 94 household contacts were screened. 61.90% families still use chullahs for cooking. 76.1% families have overcrowding. 3) 61.90% families had inadequate ventilation 4) 19.05%families were aware about the spread of this disease. 5)Only 23.80% families practised adequate sanitation methods and precautions6) 42.8% Index cases had a history of smoking. 7) 44.4% 4 continue to smoke with infection. The association of adequate sanitation with presence of awareness was found to be statistically significant. (p-value

The stereochemistry of the lipophilic side chain of (+)-rakicidin F had not been determined until recently. Using our lithiation-borylation methodology ("assembly line synthesis") we were able to efficiently prepare the all-syn isomer as well as the C-21 epimer of the side chain, and comparison with the natural product suggested that the natural product had all-syn stereochemistry. Completion of the total synthesis using a macrolactamization of the northern amide enabled us to confirm Wang and Chen's stereochemical findings for the structure of (+)-rakicidin F.

Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children.The investigators aimed to obtain safety and efficacy data for edoxaban in children.We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients 18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.The modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions).Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).

Foreign body aspiration (FBA) is a common issue in pediatric emergencies, with regional variations. Various cultures and foods, parents' and physicians' inadequate experience, and lack of bronchoscopy equipment are some attributable factors in the regional variation of FBA.To more accurately represent the demographic characteristics of aspirated foreign bodies (FBs) across various continents, this review attempted to provide organized information based on the reviewed articles.A search was conducted in PubMed/PubMed Central, EMBASE, and google scholar. From the 36 included articles, information on age, gender, bronchoscopy type, type of FB, location, history of choking, and time elapsed between aspiration and admission were extracted.A total of 14,469 cases were evaluated. According to the findings, children under two accounted for more than 75% of FBAs. Nuts and seeds were the most common FBs in most countries, whereas plastic and metal objects had higher rates in Brazil, and calcified objects were more prevalent in Thailand. The right bronchus was the most frequent location, and rigid bronchoscopy was the most often utilized type of bronchoscope. In addition, a significant percentage of patients were referred to the emergency rooms in the first 12-24 h following the aspiration incident. Moreover, Asian patients reported more choking history, and Europeans had fewer witnesses of FBA.There is a lack of standardized reporting systems and organized guidelines in pediatric FBA. To select the ideal time for endoscopies and create educational programs, a collaboration between experienced researchers, pediatric pulmonologists, radiologists, and otolaryngologists is required.

This research plans to explore the risks of the investment claims involved in the ongoing technology transfers to COVID-19 vaccine manufacturers based on the recently approved ‘Agreement on Trade-Related Aspects of Intellectual Property Rights' (TRIPS) waiver. These investment claims are based on the various intellectual property rights protected under international investment laws. The recently approved TRIPS waiver only deals with the patent rights involved in producing the COVID-19 vaccine but does not deal with the other related intellectual property rights such as trade secrets. This work sounds the alarm of investment dispute for the mass-production of vaccines based on the TRIPS waiver. The research suggests a plan by which the Indian government can address the global issue of COVID-19 technology transfer in India.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has emerged as a promising imaging tool in prostate cancer diagnosis. PSMA PET/CT radiotracers are produced in-house (gallium-68, eg,Hospitals and diagnostic facilities currently conducting PSMA PET/CT in Australia in metropolitan and regional areas completed a survey of PSMA PET/CT throughput, radiotracers involved, and the cost of assets, departmental staffing, consumables, and occupancy. Total costs were estimated using a top-down microcosting approach, involving identifying all relevant cost components and valuing each component for the average patient, and a gross costing approach, involving apportioning cost components at an aggregated level.Data were collected from 8 facilities. The most common radiotracer used wasThis study provides a detailed and accurate estimation of the cost of PSMA PET/CT in Australia. These costs can be used as a benchmark to identify potential efficiencies and help policy makers set the appropriate reimbursement rate for this procedure. The use of data from facilities using different radiotracers in metropolitan and regional areas and with different throughput increases the generalizability of the results, especially in countries with similar health systems.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.

The seed-borne mycopathogen Fusarium verticilliodes is a serious and deleterious pathogen causing substantial losses of rice seeds and grains. Rice seeds are prone to infestation at all points of the production chain and the fungal pathogen continues dormant devastation even during storage, adversely affecting the seed parameters. Its control is compromised due to the nonavailability of recommended fungicides during storage. Nanotechnological interventions can provide effective and ecofriendly alternative against mycopathogens during resting periods. Herein, the zinc sulfide-meerschaum nano bio-matrix (nZnS-MR) is presented to show this strategy, which worked well against F. verticilliodes when applied on freshly harvested rice seeds during 6 months of storage.The healthy, smooth and rounded girths of F. verticilloides mycelium were reduced with loss of turgidity, disrupting the hyphal exterior architecture, during in vitro treatment with nZnS-MR, endorsed by staining methodology, crystal violet and intracellular soluble protein leakage assays. In vivo application on rice seeds optimized 750 μg gnZnS-MR is presented as an ecofriendly, biocompatible, bio-efficient, profertilization, cost-effective green material for the control of F. verticilliodes with rice seed invigorating effect, describing it as new a nano-generation material for efficient storage application.

Background and purposeNuclear factor erythroid 2-related factor 2 (NRF2; encoded by the NFE2L2 gene) has been implicated in outcome following aneurysmal subarachnoid haemorrhage (aSAH) through its activity as a regulator of inflammation, oxidative injury and blood breakdown product clearance. The aim of this study was to identify whether genetic variation in NFE2L2 is associated with clinical outcome following aSAH.MethodsTen tagging single nucleotide polymorphisms (SNPs) in NFE2L2 were genotyped and tested for association with dichotomized clinical outcome, assessed by the modified Rankin scale, in both a discovery and a validation cohort. In silico functional analysis was performed using a range of bioinformatic tools.ResultsOne SNP, rs10183914, was significantly associated with outcome following aSAH in both the discovery (n = 1007) and validation cohorts (n = 466). The risk of poor outcome was estimated to be 1.33-fold (95% confidence interval 1.12–1.58) higher in individuals with the T allele of rs10183914 (pmeta-analysis = 0.001). In silico functional analysis identified rs10183914 as a potentially regulatory variant with effects on transcription factor binding in addition to alternative splicing with the T allele, associated with a significant reduction in the NFE2L2 intron excision ratio (psQTL = 1.3 × 10−7).ConclusionsThe NFE2L2 SNP, rs10183914, is significantly associated with outcome following aSAH. This is consistent with a clinically relevant pathophysiological role for oxidative and inflammatory brain injury due to blood and its breakdown products in aSAH. Furthermore, our findings support NRF2 as a potential therapeutic target following aSAH and other forms of intracranial haemorrhage.

A shift to lifetime management has gained more focus with the approval of low-risk transcatheter aortic valve replacement (TAVR). This paper is therefore focused on the different approaches for lifetime management. Herein we discuss the procedural safety, durability, performance, and future options for each lifetime management strategy. In younger patients that elect to undergo surgical aortic valve replacement (SAVR), options for bioprosthetic failure are TAV-in-SAV or redo SAVR. Among patients that undergo TAVR, options for valve failure include TAVR explant with SAVR or TAV-in-TAV. Additionally, there are patients who may require a third valvular intervention. The initial therapy may limit re-intervention options down the road. This review discusses how options for future therapies affect the decision of SAVR vs TAVR in younger patients.

Interferon-γ (IFN-γ) is an essential pro-inflammatory cytokine against tuberculosis (TB). To initiate immune response, IFN-γ binds to its receptor complex which consists of two subunits IFN-γ receptor 1 (IFN-γR1) and IFN-γ receptor 2 (IFN-γR2). The deficiency in either receptor subunit can alter IFN-γ signalling thus influencing host susceptibility to TB. In the present study IFN-γ receptor expression at transcriptional and translational level was analysed in pulmonary TB patients from North India. A total of 46 pulmonary TB patients (at 0 day of anti-tuberculosis therapy) and 48 healthy controls (HCs) were recruited. It was found that the mRNA expression of IFN-γR1 was decreased in male TB patients (p = 0.003). The surface expression of IFN-γR1 (p = 0.0005) and IFN-γR2 (p = 0.024) was also found to be decreased in male TB patients. In conclusion, we found sex-dependent regulation of IFN-γR1 and IFN-γR2 expression in pulmonary TB patients of studied population.

Background: Cerebrovascular complaint is the third most common cause of death in high-income countries after cancers and ischemic heart complaint and the most common cause of severe physical disability. In India, studies estimate that prevalence of stroke varies from 116 to 163 per population. According to ICMR, stroke is the 4th leading cause of death and the 5th leading cause of disability acclimated lifetime (DALY). Stroke is the most common clinical incarnation of Cerebrovascularcomplaint and results in occurrences of brain dysfunction due to focal ischemia or Haemorrhage. Subarachnoid Haemorrhage (SAH) and cerebral venous thrombosis (CVT) will be bandied independently since their pathophysiology, clinical instantiations, and operation are distinct from a stroke. Material &Methods: An 83 years old male K/ H/ O HTNwas diagnosed with an AvaranajanyaPakshaghata with a clinical point. There was a loss of function in the left lower and upper limbs. He was not able to stand without proper support. He was having weakness of the left upper and lower limbs. He was treated with Shaman Chikitsa followed by ShodhanChikitsa as SarvanagaAbhyanga, Marsha Nasya, ShashtiShaliPindaSwedana, Shirodhara, AnuvasanaBasti, and NiruhaBasti for 15 days. Result: The patient was assessed with gold standard stroke parameters, i.e., Barthel Index & National Institute of Health Stroke Scale (NIH-SS), in which scores were turned from 15 & 21 to 65 & 9, respectively. Moreover, significant changes and improvements were observed in clinical features OF Pakshaghata before and after treatment. Conclusion: In this case, there is an involvement of Aama as an Avarana on Vata, which is vitiating the VataRoga and causes Pakshaghat.This first line of Treatment was under the elimination of the Aama involvement from Chief Complaints. It was done by Deepana- Pachana medicine as Shaman Chikitsa. After that, the ShodhanChikitsa was started by gaining the Nirama condition of Doshas. A significant improvement was observed by combining the Shaman and ShodhanChikitsa strategically.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl4 treatment. Our data demonstrate that disruption to circadian rhythm primes HSCs towards an accelerated fibrotic response which worsens liver disease.

Due to the significant seismic sensitivity of the Himalayan province, any structure constructed without sufficient knowledge of its structural behaviour cannot be termed as earthquake resistant. Apart from that vernacular architecture of Himalayan states can be classified as earthquake-resistant due to the fact that some of the structures have been standing since ages withstanding several past earthquakes. Koti Banal of Uttarakhand, Kath Kuni of Himachal Pradesh and Dhajji Dewari of Kashmir are examples of centuries old culture of seismic awareness. In order to comprehend these structures completely we have identified the pocket points of these structures and an overview of the known earthquake-resistant vernacular masonry building typologies found along the Himalayan range is presented here. Along with an assessment of the seismic resilient characteristics, a critically reviewed load transfer mechanism of the typology has been presented in the study. The research presented here shows that it is feasible to design and construct earthquake-resistant structures utilising locally available materials and traditional construction techniques, provided that the identified earthquake-resilient elements are assessed and implemented properly. Furthermore to strengthen these structures some retrofitting techniques are suggested that might safeguard these structures for another hundreds of year.