The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

BACKGROUND: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused. OBJECTIVE: The aim was to identify genetic risk factors for PD in a South Asian population. METHODS: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO. RESULTS: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease. CONCLUSIONS: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Autologous versus synthetic midurethral transobturator sling: A systematic review and meta-analysis of outcomes.

INTRODUCTION: There have been concerns around the use of synthetic mesh for stress urinary incontinence (SUI) surgery with a renewed interest in the use of autologous tissues. Recently, an autologous transobturator sling (aTOT) has been described, but the comparative data with synthetic transobturator sling (sTOT) is limited. The objective of this systematic review and meta-analysis was to assess the outcome of aTOT and compare it with sTOT. METHODS: A systematic search of PubMed, Scopus, and Web of Science databases was performed and all articles available up to December 31, 2023 were screened. Studies reporting on the outcomes of aTOT and those comparing aTOT with sTOT were included. This review was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Eleven studies evaluating 323 patients that met the criteria were included in the final analysis, of which 6 were single arm (155 patients) and 5 were comparative. In single-arm studies, the pooled success rate, defined as negative cough stress test at 12 months follow-up was 96.8%, 3.8% had postoperative urinary retention, 6.1% had graft site-related complications and 7.6% required additional intervention for persistent SUI. The overall complication rate was 20.6% and there were no Clavien III-V complications. aTOT had similar success and complication rates when compared with sTOT but had a significantly longer operative time (weighted mean difference: 22.35 min, p < 0.00001) and superior sexual function outcomes. CONCLUSIONS: aTOT, at short-term follow-up (12 months), has similar efficacy and complication rates when compared to sTOT. However, given that the data is limited and not of very good quality, and the fact that long-term follow-up is not available, further studies are required to better define the role of aTOT in the management of female patients with SUI.

Urodynamic assessment of detrusor function in the very acute phase of traumatic spinal cord injury: A prospective cohort study.

Introduction: The bladder is believed to be acontractile due to the phase of spinal shock and there is a lack of data on the detrusor function within the first few days after spinal cord injury (SCI). This study intended to assess the detrusor function with invasive urodynamics (UDS) during the first 15 days of SCI. Methods: This prospective observational study was carried out from January 2020 to June 2021 and consecutive stable patients older than 18 years of age who had a history of traumatic SCI within the past 15 days were screened for inclusion. For each patient, the International Standards for Neurological Classification of SCI Worksheet was filled. All patients underwent bedside invasive UDS within 15 days of injury. Results: There were a total of 41 patients with a mean age of 35 years. The thoracic cord was most commonly involved (46.3%) with Type A AISA grade being the most common (68.2%). The mean duration of injury at the time of UDS was 6 days. Abnormality in the filling phase could be identified in six patients. Three patients had neurogenic detrusor overactivity (NDO), with one having a high-pressure phasic NDO and one having a sustained NDO. Two patients had poor compliance and one had borderline poor compliance. None of the patients generated any detrusor pressure during voiding cystometry. Conclusions: In patients with SCI, 14.5% of the patients had abnormal findings during the filling phase on the UDS performed within 15 days of the injury. These findings are in stark contrast to the traditional understanding that the detrusor is acontractile during the early phase of the SCI and merit further evaluation.

De novogenomic analysis ofEnterobacter asburiaeEBRJ12, a plant growth-promoting rhizobacteria isolated from the rhizosphere of Phaseolus vulgarisL.

AIM: Environmental stresses such as water deficit induced stress are one of the major limiting factors in crop production. However, some plant growth-promoting rhizobacteria (PGPR) can promote plant growth in such adverse condition. Therefore, the objective was to isolate rhizospheric bacteria from Phaseolus vulgaris L. growing in a drought-affected soil and to analyze its plant growth promoting (PGP) efficacy to black gram (Vigna mungo L.) and Bhut jolokia (Capsicum chinense Jacq.). Whole-genome sequencing of the potential bacteria was targeted to analyze the genetic potential of the isolate as a plant growth-promoting agent. METHODS AND RESULTS: The isolate Enterobacter asburiae EBRJ12 was selected based on its PGP efficacy, which significantly improved plant growth and development. The genomic analysis revealed the presence of one circular chromosome of size 4.8 Mb containing 16 genes for osmotic stress regulation including osmotically inducible protein osmY, outer membrane protein A precursor ompA, aquaporin Z, and an operon for osmoprotectant ABC transporter yehZYXW. Moreover, the genome has a complete genetic cluster for biosynthesis of siderophore Enterobactin and siderophore Aerobactin.The PGP effects were verified with black gram and Bhut jolokia in pot experiments. The isolate significantly increased the shoot length by 35.0% and root length by 58.0% of black gram, while 41.0% and 57.0% of elevation in shoot and root length were observed in Bhut jolokia compared to non-inoculated plants. CONCLUSIONS: The EBRJ12 has PGP features that could improve the growth in host plants, and the genomic characterization revealed the presence of genetic potential for plant growth promotion.

Environmental sustainability in robotic and laparoscopic surgery: systematic review.

BACKGROUND: Minimally invasive surgical (MIS) techniques are considered the gold standard of surgical interventions, but they have a high environmental cost. With global temperatures rising and unmet surgical needs persisting, this review investigates the carbon and material footprint of MIS and summarizes strategies to make MIS greener. METHODS: The MEDLINE, Embase, and Web of Science databases were interrogated between 1974 and July 2021. The search strategy encompassed surgical setting, waste, carbon footprint, environmental sustainability, and MIS. Two investigators independently performed abstract/full-text reviews. An analysis of disability-adjusted life years (DALYs) averted per ton of carbon dioxide equivalents (CO2e) or waste produced was generated. RESULTS: From the 2456 abstracts identified, 16 studies were selected reporting on 5203 MIS procedures. Greenhouse gas (GHG) emissions ranged from 6 kg to 814 kg CO2e per case. Carbon footprint hotspots included production of disposables and anaesthetics. The material footprint of MIS ranged from 0.25 kg to 14.3 kg per case. Waste-reduction strategies included repackaging disposables, limiting open and unused instruments, and educational interventions. Robotic procedures result in 43.5 per cent higher GHG emissions, 24 per cent higher waste production, fewer DALYs averted per ton of CO2, and less waste than laparoscopic alternatives. CONCLUSION: The increased environmental impact of robotic surgery may not sufficiently offset the clinical benefit. Utilizing alternative surgical approaches, reusable equipment, repackaging, surgeon preference cards, and increasing staff awareness on open and unused equipment and desflurane avoidance can reduce GHG emissions and waste.

Clinical Study of 668 Indian Subjects with Juvenile, Young, and Early Onset Parkinson's Disease.

OBJECTIVE: To determine the demographic pattern of juvenile-onset parkinsonism (JP, <20 years), young-onset (YOPD, 20-40 years), and early onset (EOPD, 40-50 years) Parkinson's disease (PD) in India. MATERIALS AND METHODS: We conducted a 2-year, pan-India, multicenter collaborative study to analyze clinical patterns of JP, YOPD, and EOPD. All patients under follow-up of movement disorders specialists and meeting United Kingdom (UK) Brain Bank criteria for PD were included. RESULTS: A total of 668 subjects (M:F 455:213) were recruited with a mean age at onset of 38.7 ± 8.1 years. The mean duration of symptoms at the time of study was 8 ± 6 years. Fifteen percent had a family history of PD and 13% had consanguinity. JP had the highest consanguinity rate (53%). YOPD and JP cases had a higher prevalence of consanguinity, dystonia, and gait and balance issues compared to those with EOPD. In relation to nonmotor symptoms, panic attacks and depression were more common in YOPD and sleep-related issues more common in EOPD subjects. Overall, dyskinesias were documented in 32.8%. YOPD subjects had a higher frequency of dyskinesia than EOPD subjects (39.9% vs. 25.5%), but they were first noted later in the disease course (5.7 vs. 4.4 years). CONCLUSION: This large cohort shows differing clinical patterns in JP, YOPD, and EOPD cases. We propose that cutoffs of <20, <40, and <50 years should preferably be used to define JP, YOPD, and EOPD.

Development & validation of scales to assess stigma related to COVID-19 in India.

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

The impact of the COVID-19 pandemic on global neurosurgical education: a systematic review.

The COVID-19 pandemic has disrupted neurosurgical training worldwide, with the shutdown of academic institutions and the reduction of elective surgical procedures. This impact has disproportionately affected LMICs (lower- and/or middle-income countries), already burdened by a lack of neurosurgical resources. Thus, a systematic review was conducted to examine these challenges and innovations developed to adapt effective teaching and learning for medical students and neurosurgical trainees. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and The Cochrane Handbook of Systematic Reviews of Interventions. MEDLINE, PubMed, Embase and Cochrane databases were accessed, searching and screening literature from December 2019 to 5th December 2020 with set inclusion and exclusion criteria. Screening identified 1254 articles of which 26 were included, providing data from 96 countries. Twenty-three studies reported transition to online learning, with 8 studies also mentioned redeployment into COVID wards with 2 studies mentioning missed surgical exposure as a consequence. Of 7 studies conducted in LMICs, 3 reported residents suffering financial insecurities from reduced surgical caseload and recession. Significant global disruption in neurosurgical teaching and training has arisen from the COVID-19 pandemic. Decreased surgical exposure has negatively impacted educational provision. However, advancements in virtual technology have allowed for more affordable, accessible training especially in LMICs. Using this, initiatives to reduce physical and mental stress experienced by trainees should be paramount.

Twelve tips for successfully getting involved in research as a medical student.

Medical research is a highly competitive yet vital part of medical training, spanning all specialties. Extra-curricular, research-related activities are a key method by which students develop interest in their field of choice, and a competitive edge in medical students. The lack of research education and opportunities within medical school teaching tends to force medical students to look beyond their degree to obtain this experience, and is often the reason why students have little research involvement whilst in medical school. Self-reflecting on one's personality and suitability for different types of research is vital, as well as understanding the nature of research and preparing appropriately before undertaking projects. This paper presents twelve tips for medical students who are interested in pursuing research, offering targeted strategies to get involved.

Genetic characterization of dengue virus serotype 2 isolated from dengue fever outbreaks in eastern Uttar Pradesh and western Bihar, India.

Dengue (DEN) is the most common cause of mosquito-borne endemic viral diseases in the tropical and subtropical countries. DEN outbreaks associated with multiple dengue virus (DV) serotypes have been regularly reported in different parts of India. This study was done during DEN outbreaks in 2015 to 2016 in UP and Bihar where DEN-2 was found as the only prevalent serotype. DV-2 was the only serotype amplified in serotype-specific reverse-transcription polymerase chain reaction from sera of 210 (65.21%) out of 322 DV NS1 antigen-positive patients. Further genetic analysis based on full-length envelope (E) protein sequence derived from patient's sera as well as DV isolate showed the circulation of lineages I and III of DV-2 cosmopolitan genotype during 2015 and lineage II during 2016. Finally, the phylogenetic analysis using the E gene sequence revealed that these DV-2 strains have a close genetic relationship with the recently reported DV-2 genotypes from DEN outbreaks reported from different parts of north India. These results showed the circulation of cosmopolitan genotype of DV-2 in eastern Uttar Pradesh and western Bihar, India. The genetic database generated on circulating DV strains in this study will be useful as reference for disease surveillance and strengthening laboratory diagnosis protocols.

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study.

OBJECTIVE: To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI). METHODS: This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline. RESULTS: A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H2 O to 41 cm H2 O (p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment. CONCLUSION: Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

"Mesh free" autologous transobturator mid urethral sling placement for predominant stress urinary incontinence: A pilot study.

AIMS: To assess the efficacy and safety of autologous mid-urethral sling (MUS) in women with predominant stress urinary incontinence (SUI). MATERIALS AND METHODS: This prospective cohort study included adult women with predominant SUI seen in our urology clinic between January 2018 and March 2019. Patients with: negative cough stress test, history of prior incontinence surgery, urogenital malignancy, pelvic radiation, neurological disease, body mass index more than 40 kg/m2 , the presence of more than Stage I pelvic organ prolapse, active urinary tract infection, maximum flow rate less than 15 ml/sec, postvoid residual urine more than 100 ml, abdominal leak point pressure less than 60 cm of H2 O, and pregnant women were excluded. Eligible patients underwent a transobturator MUS procedure using rectus fascia as a sling. Before the procedure, patients filled the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptom (ICIQ-FLUTS) and the Female Sexual Function Index (FSFI) questionnaire. Urinary outcomes were assessed at 3- and 12-months while sexual outcomes were assessed at 12-months. RESULTS: Thirty patients with median age of 44.5 years were included. All patients had a negative cough stress test during follow up. A significant improvement was noted in the ICIQ-FLUTS scale, bother scale, filling and incontinence subscales at 3 and 12 month follow-up. A significant improvement was also noted in the FSFI full scale score and FSFI domains of mean sexual desire, arousal and lubrication at 12 months follow-up. Two patients developed voiding dysfunction requiring urethral dilatation. CONCLUSION: Autologous transobturator MUS surgery appears to be safe and efficacious in the short term. More research is needed to clarify its role in the surgical management of SUI in women.

Neurological safety and efficacy of darifenacin and mirabegron for the treatment of overactive bladder in patients with history of cerebrovascular accident: A prospective study.

OBJECTIVES: To evaluate the neurological safety and clinical efficacy of darifenacin and mirabegron in patients with a history of cerebrovascular accident (CVA) who had overactive bladder (OAB) symptoms. METHODS: This prospective randomized study, approved by the institute's ethics committee, was carried out at a tertiary care center from December 2018 to June 2020. Treatment naïve adult patients with a past history of CVA with stable neurological status for atleast past 3 months with symptoms of OAB for 3 or more months were included. Eligible patients received either darifenacin or mirabegron for a period of 3 months and various parameters on the 3-day International Consultation on Incontinence Questionnaire (ICIQ) bladder diary, the Montreal Cognitive Assessment-Basic score (MoCA-B), and the adverse events at 3 months posttreatment were compared to that at the baseline. RESULTS: A total of 60 patients were included, 30 in each arm. After 3 months of treatment with darifenacin or mirabegron, the majority of the ICIQ bladder diary parameters improved and there was no deterioration in the cognitive function as noted on the MoCA-B score in either of the arms. On intergroup comparison, the mean change in bladder diary parameters and the MoCA-B scores was similar between the two groups. CONCLUSION: Darifenacin and mirabegron, in the short term, do not adversely affect the cognitive function in patients with a history of CVA with OAB symptoms. Both are safe and effective treatment options in patients with OAB post-CVA.

Neurological manifestations of coronavirus disease 2019: exploring past to understand present.

SARS-CoV-2 infection, resulting in Coronavirus disease 2019 (COVID-19), has significantly affected the entire world. It was labelled a pandemic by World Health Organization. Although it commonly produces respiratory symptoms, neurological features have been described. Neurological manifestations may vary from non-specific symptoms such as headache, dizziness, myalgia and/or fatigue, olfactory or taste dysfunction to specific syndromes including meningitis, stroke, acute transverse myelitis and Guillain-Barre syndrome. This review describes potential pathogenetic mechanisms and neurological manifestations of COVID-19 along with its management. Considering structural and pathogenetic similarity of SARS-CoV-2 with SARS-CoV and MERS viruses, we compared their neurological manifestations and mentioned few features expected in COVID-19 in future. Interestingly, many COVID-19 cases may present with pure neurological manifestations at onset with non-neurological features manifesting few days later and we propose the term "Neuro-COVID syndrome" for such cases. Awareness of neurological manifestations may facilitate its management and improve outcome in such patients.

Incidence of posterior vessel wall puncture during ultrasound guided vascular access: Short axis versus long axis approach.

BACKGROUND AND AIMS: Posterior vessel wall puncture (PVWP) is a common complication of ultrasound (US) guided central venous cannulation. We evaluated and compared the frequency of PWVP of internal jugular vein using short axis (SA) and long axis (LA) approach of US-guided needle cannulation. As a secondary objective incidence of carotid puncture was assessed. MATERIAL AND METHODS: Prospective, single-blinded, cross over, observational study at Urban Level I Neuroanesthesiology and Critical Care Department. Residents receiving standard education on ultrasound-guided central venous cannulation were asked to place an US-guided catheter using either short axis or long axis approach on a human torso mannequin. During the procedure, the path of the needle was carefully observed by the investigator for any PVWP and carotid puncture without interference with the placement procedure. The confidence level of the resident for the intraluminal placement of the needle tip was measured on a 10-point Likert scale. RESULTS: Forty residents participated in the study. The incidence of PVWP in SA and LA group was 40% and 17.5% respectively and was statistically significant (p = 0.026). There was no incidence of carotid artery puncture in either of the group. The mean confidence of intraluminal placement of needle was significantly higher in the LA group (8.32) as compared to the SA group (5.95). CONCLUSION: Lower incidence of PVWP was seen in LA as compared to the SA approach during US-guided IJV cannulation in phantom in residents having previous experience of CVC (central venous cannulation) in landmark technique only. Participants were more confident about intraluminal needle placement in the LA group compared to the SA group.

Efficacy and Acceptance of a Lombard-response Device for Hypophonia in Parkinson's Disease.

OBJECTIVE: The purpose of this study was to examine the effectiveness, satisfaction, and acceptance of a low-cost Lombard-response (LR) device in a group of individuals with Parkinson's disease (IWPD) and their communication partners (CPs). METHOD: Sixteen IWPD and hypophonia and their CPs participated in the study. The IWPD wore a LR device that included a small MP3 player (Sony Walkman) and headphones playing a multi-talker noise audio file at 80 dB during lab-based speech tasks and during their daily conversational speech over a 2-week device trial period. Outcome measures included average conversational speech intensity and scores on a questionnaire related to speech impairment, communication effectiveness, and device satisfaction. RESULTS: Conversational speech intensity of the IWPD is increased by 7 to 10 dB with the LR device. Following a 2-week trial period, eight of the IWPD (50%) gave the LR device moderate-to-high satisfaction and effectiveness ratings and decided to purchase the device for long-term daily use. At the 4-month follow-up, none of the IWPDs were still using the LR device. Device rejection was related to discomfort (loudness), headaches, interference with cognition, and difficulty controlling device. CONCLUSION: Short-term acceptance and satisfaction with the LR device was moderate, but long-term acceptance, beyond 4 months, was absent. Future studies are required to determine if other types of low-cost LR devices can be developed that improve long-term efficacy and device acceptance in IWPD and hypophonia.

Efficacy and safety of mirabegron for the treatment of low compliance bladder resulting from sacral/infrasacral lesions: A prospective study.

OBJECTIVE: To assess the efficacy and safety of mirabegron in patients with sacral/infrasacral lesions who have an acontractile detrusor and develop a low compliance bladder. METHODS: This prospective study included adult patients with acontractile detrusor as a result of sacral/infrasacral lesions who develop a low compliance bladder (compliance <20 mL/cmH2 O). All patients were asked to make a 48-h clean intermittent catheterization diary and underwent invasive urodynamics evaluation at the baseline, and were started on mirabegron 50 mg once daily. Patients were re-evaluated at 6 weeks with a repeat clean intermittent catheterization diary and invasive urodynamics, and the efficacy and safety of mirabegron was assessed. RESULTS: A total of 17 patients were included. After 6 weeks of mirabegron therapy, the number of patients reporting leakage in between clean intermittent catheterization reduced from seven to two (P = 0.02), the end filling pressures reduced from 41.4 to 15.1 cmH2 O (P = 0.003), the compliance increased from 9.8 to 99.9 mL/cmH2 O (P = 0.000), and the number of patients where the end filling pressure was >40 cmH2 O reduced from eight to one (P = 0.02). The cystometric bladder capacity did not change significantly. Similar effects were noted in patients who were already on clean intermittent catheterization or were started on clean intermittent catheterization at inclusion in the study. Mirabegron was well tolerated, none of the patients discontinued therapy or reported major side-effects. CONCLUSIONS: Mirabegron reduces end filling pressure, improves compliance and is safe in patients with a low compliance bladder resulting from a sacral/infrasacral lesion.

A Study of the Serum Uric Acid Level as Prognostic Indicator in Acute Myocardial Infarction.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in present days. Recent epidemiological and clinical evidences suggest that serum uric acid can be one of the useful markers in assessing the risk of mortality in acute myocardial infarction. OBJECTIVE: To find out the association in serum uric acid level and Killip classes and ejection fraction. METHODOLOGY: It was an observational prospective study. 100 patients of acute myocardial infarction were enrolled and physical examination with special reference to Killip classification, ECG, 2D- Echocardiogram, Serum uric acid and all routine investigations were carried out on 0, 3rd and 7th day. Serum uric acid and Killip class and ejection fractions on day 0, day 3 and day 7 were compared. RESULTS: In this present study majority of the patients were in the age group of >50 years (68%). There was statistically significant increase in uric acid levels with increasing Killip class on day 0, day 3 and day 7. Mean serum uric acid level was 4.4 mg/dl in Killip class I, 7.01 mg/dl in class II, 8.29 mg/dl in class III, and 9.87 mg/ dl in class IV on day 0; 4.46 mg/dl in Killip class I, 7.09 mg/dl in class II, 8.53 mg/ dl in class III, and 9.43 mg/dl in class IV on day 3; 4.72 mg/dl in Killip class I, 6.62 mg/dl in class II, on day 7. There was statistically significant negative correlation (p-value 0.0009, 0.001, 0.0326 at day 0, 3 & 7) between serum uric acid levels and ejection fraction at all the three occasions i.e. day 0, day 3 and day 7. CONCLUSION: The present study concludes that serum uric acid level have significant association with Killip class, left ventricular failure and mortality i.e. higher the serum uric acid, higher the Killip class, more severe left ventricular dysfunction and higher the mortality.The present study concludes that serum uric acid level have significant association with Killip class, left ventricular failure and mortality i.e. higher the serum uric acid, higher the Killip class, more severe left ventricular dysfunction and higher the mortality.

A stochastic model for post-transcriptional regulation of rare events in gene expression.

Post-transcriptional regulation of gene expression is often a critical component of cellular processes involved in cell-fate decisions. Correspondingly, considerable efforts have focused on modeling post-transcriptional regulation of stochastic gene expression and on quantifying its impact on the mean and variance of protein levels. However, the impact of post-transcriptional regulation on rare events corresponding to large deviations in gene expression is less well understood. Here, we study a simple model involving post-transcriptional control of gene expression and characterize the impact of regulation on large deviations in activity fluctuations. We derive analytical results for the large deviation function for protein production rate and for the corresponding driven process which characterizes system fluctuations conditional on the rare event. Our results suggest that fluctuations in burst size rather than frequency play a dominant role in controlling rare events. The results derived also provide insight into how post-transcriptional regulation can be used to fine-tune the probability of rare fluctuations and to thereby control phenotypic variation in a population of cells.

Constraining the complexity of promoter dynamics using fluctuations in gene expression.

Gene expression is an inherently stochastic process with transcription of mRNAs often occurring in bursts: short periods of activity followed by typically longer periods of inactivity. While a simple model involving switching between two promoter states has been widely used to analyze transcription dynamics, recent experimental observations have provided evidence for more complex kinetic schemes underlying bursting. Specifically, experiments provide evidence for complexity in promoter dynamics during the switch from the transcriptionally inactive to the transcriptionally active state. An open question in the field is: what is the minimal complexity needed to model promoter dynamics and how can we determine this? Here, we show that measurements of mRNA fluctuations can be used to set fundamental bounds on the complexity of promoter dynamics. We study models wherein the switching time distribution from transcriptionally inactive to active states is described by a general waiting-time distribution. Using approaches from renewal theory and queueing theory, we derive analytical expressions which connect the Fano factor of mRNA distributions to the waiting-time distribution for promoter switching between inactive and active states. The results derived lead to bounds on the minimal number of promoter states and thus allow us to derive bounds on the minimal complexity of promoter dynamics based on single-cell measurements of mRNA levels.