The Role Of Histone Demethylase Kdm6a In Mouse Coronavirus Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of acute respiratory coronavirus disease 2019 (COVID-19), a disease that erupted into a global pandemic in March of 2020.2 Recently, a genome wide CRISPR screen was performed on SARS-lineage coronaviruses and two additional recombinant viruses; the screen revealed host genes essential to coronavirus pathogenesis and entry.7 The screen identified KDM6A, a histone demethylase, as an important pro-viral gene.7 Building upon this observation, in this thesis, I explore the role of Kdm6a in murine hepatitis virus (MHV), a type of mouse coronavirus. MHV is the prototypical model for studying SARS-CoV-2 pathogenesis due to the ease of biological safety protocols and its ability to help us characterize coronaviruses generally.41 The Kdm6a gene encodes enzyme lysine specific demethylase 6A that is found in many cells of the body.8 Kdm6a functions as a histone demethylase, which helps increase activity of certain genes, specifically developmental genes.8 Though much is not known about Kdm6a’s implication in coronavirus infection, preliminary data suggests that Kdm6a is essential to MHV-A59 and MHV-3 infection. In our first aim, we performed RT-qPCR to elucidate Kdm6a’s role in viral entry. We found Kdm6a knockout results in reduced Ceacam1 expression, the receptor for MHV. For our second aim, we designed mutated Kdm6a constructs to assess which domains of Kdm6a are important in viral infection. We proceeded to run rescue assays to observe expression of Kdm6a in Kdm6a deficient cells. Though we did not observe expression, there are likely explanations as to why these experiments did not work. To this end, the present study suggests that Kdm6a is important in viral entry, possibly through regulation of receptor expression, but which of its domains are responsible remains to be elucidated

An examination of maladaptive perfectionism, perfectionistic self-presentation, wellbeing and the disclosure of mental health difficulties

Aims. Clinical psychology training is demanding, and the multiple competing demands can negatively affect trainees’ wellbeing. This study explored trainees’ levels of wellbeing, maladaptive perfectionism and perfectionistic self-presentation, and explored the relationship between perfectionism and wellbeing. It evaluated the effectiveness of a brief CBT-based perfectionism workshop in reducing unhealthy perfectionism and perfectionistic self-presentation, and altering trainees’ likelihood of, and comfort with, disclosing mental health problems and personal difficulties to others. It also examined whether these changes persisted over time. Methods. The workshop was delivered at four UK clinical psychology doctoral programmes. At the start of the workshop, 117 trainees completed an online survey examining wellbeing, maladaptive perfectionism, perfectionistic self-presentation, and their likelihood of, and comfort with talking about mental health problems and personal difficulties with three recipients: placement supervisor, a member of course staff and a fellow trainee. The survey was repeated immediately after the workshop, and at 11-weeks follow-up (n = 35). Results. Wellbeing deteriorated over time and was negatively correlated with maladaptive perfectionism and perfectionistic self-presentation. The workshop reduced maladaptive perfectionism and perfectionistic self-presentation and, excluding comfort with disclosing mental health problems to course staff, increased trainees’ likelihood and comfort with disclosing mental health problems to all recipients. Conversely, the intervention had no effect on disclosure of personal difficulties. At follow-up, only changes in perfectionism were maintained. Conclusions. The results demonstrate the effectiveness of the workshop at reducing perfectionism and breaking down barriers to disclosure in the training environment. Future research should therefore seek to evaluate the effectiveness of this workshop with larger and more diverse trainee cohorts

Second trimester abortion- mifepristone and misoprostol or misoprostol alone?

Background: From historical times termination of pregnancy was practiced with or without legal and social sanctions. Over the last few years, induced abortions have gained more popularity because of safe techniques and medications available. Induced abortion means willful termination of pregnancy before the period of viability. Medical abortion in the second trimester with misoprostol alone has been shown to be affective, although in comparison with the combination of mifepristone and misoprostol, misoprostol-only protocols have required higher doses, side effects are more common and the time to complete the abortion is longer.Methods: Total of 50 eligible women were enrolled for this study and were divided in two groups of 25 each of the case group and control group. This study was conducted in the Dhiraj General Hospital, Piparia, Waghodia. Women in the case group were given Tablet Mifepristone (200 mg) orally followed by Tablet Misoprostol (200 mcg) vaginally after 24 hours which may be repeated every 6 hrs till 5 doses. Women in control group were given Tablet Misoprostol (200 mcg) vaginally which may be repeated every 6 hrs till 5 doses.Results: The combination of mifepristone and misoprostol is now an established and highly effective and safe method for medical method second trimester abortion. The combination of mifepristone with misoprostol significantly reduces the abortion to induction interval and also have fewer side effects and complications and also reduces the dose of misoprostol. Where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective, although a higher total dose is needed and efficacy is lower than for the combined regimen. Therefore, whenever possible, the combined regimen should be used.Conclusions: Mifepristone followed by misoprostol was more effective and has a shorter IAI and fewer side effects

EFFECT OF MUSTAKADI VATI IN THE MANAGEMENT OF GRAHANI DOSHA IN CHILDREN – A CASE STUDY

BACKGROUND: Grahani is the Adhishthana of Agni and Agni Dushti is the main reason of the disease. The disease Grahani Dosha is very commonly seen in present pediatric practice and it aggravates to form a critical condition if the proper care is not taken. MATERIAL AND METHOD: A 8-years-old male patient of Grahani Dosha with complaints of defecation just after taking meal, Bowel frequency 3-4 times/day, irregular bowel habit, loss of appetite, generalized weakness, occasional pain in abdomen, slow weight gain for 5-6 months was treated by Mustakadi Vati in three divided doses of 10 Vati per day after meal for 8 weeks with SukhoshnaJala. RESULT: Marked improvement was found after 8 weeks of treatment i.e., bowel frequency reduced to 1 time/day, no weakness, abdominal pain relieved, 2 kg body weight gained. Hematological parameters along with routine and microscopic investigations of stool and urine were done before and after the treatment, all were found normal. Mala Parikshana was done before treatment which showed sinking of stool in water and foul smell and after 8 weeks of treatment again Mala Parikshana was done where floating of stool in water and no foul smell were found. CONCLUSION: This case study has shown that Mustakadi Vati is effective in improving the symptoms of Grahani Dosha. Marked improvements were found in all the symptoms of Grahani Dosha in Children

A REVIEW ON ANCIENT CONCEPTS OF KUMARAGARA, KRIDABHOOMI AND KRIDANAKA W.S.R.TO PEDIATRIC CARE UNIT, PLAY GROUND AND TOYS

Ayurveda is one of the earliest medical systems that have got a strong scientific foundation formulated by experiments and observations of ancient wisdom. Kaumarbhritya (pediatrics) is one among eight branches of Ayurveda. Acharya Kashyapa has given prime importance to Kaumarbhritya for the very first time. As far as the branch pediatrics is concerned, in Ayurveda it accompanies a broad area. Virtually every aspect of a growing child is connected with play. Now days, many textbooks of pediatrics are focusing more on pediatric diseases and its management, but the concept of toys, play and its importance remain untouched. Years ago, Acharyas has described characteristics of Kumaragara (Neonatal care unit/pediatric ward), Kumaradhara (guardian), Kridanaka (toys) and Kridabhumi (play ground) which all are the pillars of a healthy and prosperous human being. Here, an effort is made to collect those aspects and validating that data with available evidence based references.

A study of effect of intra umbilical oxytocin in active management of third stage of labour

Background: Postpartum haemorrhage is a single major and leading cause of maternal morbidity and mortality. PPH is the loss of more than 500 ml blood following vaginal delivery or 1000 ml blood following caesarean section. India has a maternal mortality ratio of 167 per 1 lakh live births. The most common cause of maternal mortality is haemorrhage which accounts for 25-30% of maternal mortality of which PPH is a significant cause. Methods: 200 patients were included in this prospective observational study and divided into two groups, group A, underwent only active management of third stage of labour and group B received intra umbilical oxytocin administration in addition to AMTSL. The maternal and neonatal outcome was observed between the two and the difference was noted. Results: Mean duration of third stage of labour of group A patients was 3.89±0.89 minutes and Mean blood loss was 386±85.30 ml and that of group B patients was 1.96±0.68 minutes and 235±72.99 ml respectively. These were found to be statistically significant among all the other parameters. Conclusions: The duration of third stage of labour and the amount of postpartum blood loss was significantly less when intra umbilical injection of oxytocin was used in addition to AMTSL. So, to conclude intra umbilical vein oxytocin injection should be used routinely in addition to AMTSL in order to prevent PPH

TRIPHALAGUDUCHYADI VATI WITH DIET AND LIFESTYLE MODIFICATION IN THE MANAGEMENT OF CHILDHOOD OBESITY- A CASE REPORT

Childhood Obesity (Sthaulya) is one of the major non communicable diseases of the modern era, increasing in prevalence. Diet (Ahara) and life-style (Vihara) play significant role both in the development and control of obesity Sthaulya (obesity). As per Ayurveda texts, over consumption of energy dense foods along with sedentary lifestyle hampers the functioning of Medodhatvagni results in decrease fat metabolism hence causes obesity. So Triphalaguduchyadi Vati was chosen to break the etiopathogenesis of Sthaulya and to enhance the fat metabolism. A 16 year old, 11th standard, Hindu male child visited with parents to KB OPD, IPGTRA, Gujarat Ayurved University, Jamnagar, having chief complaint of progressive weight gain since 6-7 years. Triphalaguduchyadi Vati was intervened in appropriate dose for 8 weeks along with modified diet and lifestyle. Physical and laboratory assessments were done before and after the intervention. After 8 weeks of drug intervention, there was marked relief in symptoms, also there was significant decrease in physical and laboratory parameters. After reviewing, this case study it can be concluded that Triphalaguduchyadi Vati with modified diet and lifestyle is effective treatment regimen for Sthaulya in children

Virtual classroom proficiency-based progression for robotic surgery training (VROBOT): a randomised, prospective, cross-over, effectiveness study

Robotic surgery training has lacked evidence-based standardisation. We aimed to determine the effectiveness of adjunctive interactive virtual classroom training (VCT) in concordance with the self-directed Fundamentals of Robotic Surgery (FRS) curriculum. The virtual classroom is comprised of a studio with multiple audio-visual inputs to which participants can connect remotely via the BARCO weConnect platform. Eleven novice surgical trainees were randomly allocated to two training groups (A and B). In week 1, both groups completed a robotic skills induction. In week 2, Group A received training with the FRS curriculum and adjunctive VCT; Group B only received access to the FRS curriculum. In week 3, the groups received the alternate intervention. The primary outcome was measured using the validated robotic-objective structured assessment of technical skills (R-OSAT) at the end of week 2 (time-point 1) and 3 (time-point 2). All participants completed the training curriculum and were included in the final analyses. At time-point 1, Group A achieved a statistically significant greater mean proficiency score compared to Group B (44.80 vs 35.33 points, p = 0.006). At time-point 2, there was no significant difference in mean proficiency score in Group A from time-point 1. In contrast, Group B, who received further adjunctive VCT showed significant improvement in mean proficiency by 9.67 points from time-point 1 (95% CI 5.18-14.15, p = 0.003). VCT is an effective, accessible training adjunct to self-directed robotic skills training. With the steep learning curve in robotic surgery training, VCT offers interactive, expert-led learning and can increase training effectiveness and accessibility

New recommendations to reduce unnecessary blood tests after robot-assisted radical prostatectomy.

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