A Randomized Controlled Trial of Blood Pressure Reduction Based on Disease Control Priorities 3 in Pakistan to Manage and Control Hypertension.

INTRODUCTION: According to American Heart Association standards, hypertension is classified into three stages based on blood pressure measurements: essential hypertension, stage 1 hypertension, and stage 2 hypertension. The global target is to reduce the prevalence of high blood pressure by 25% by the year 2025. Worldwide, the prevalence of high blood pressure among men and women aged 18 and above reported to be 24% and 20%, respectively. AIM: The aim of this study was to overall reduce high blood pressure of hypertensive patients to the recommended level of 140/90 mm of Hg through implementing a non-pharmacological and multi-component intervention based on Disease Control Priorities (3rd edition). METHODS: A randomized controlled trial in which a multi-component intervention for lowering high blood pressure was tested. This was pilot-tested for its acceptance, appropriateness, and relevance, explored through an earlier formative research and desk review conducted from the available evidence. A total of 240 study participants were enrolled after obtaining informed consent. Ethical approval was obtained from the Institutional Review Board of Health Services Academy and the trial was registered in clinicaltrials.gov number NCT04336631. SPSS software version 21 was used to enter and analyze the data. RESULTS: High blood pressure of hypertensive patients in a hospital setting during 03 months yielded -23.9 mm Hg of systolic blood pressure reduction (95% confidence interval, p ≤ 0.005). A significant reduction was observed in intervention group after delivering the intervention. Compared to patients in the usual care group, improved health outcomes were achieved for diet control, reducing salt intake and increased physical exercise. In the intervention group, the mean blood pressure among male hypertensive patients was 145/90 mm Hg and in female hypertensive patients, the mean blood pressure was recorded as 140/100 mm Hg. CONCLUSION: High blood pressure was significantly reduced in hypertensive patients who adhered to a low salt diet, weight loss measures, and increased physical activity.

Hormonal and Genetic Regulatory Events in Breast Cancer and Its Therapeutics: Importance of the Steroidogenic Acute Regulatory Protein.

Estrogen promotes the development and survival of the majority of breast cancers (BCs). Aromatase is the rate-limiting enzyme in estrogen biosynthesis, and it is immensely expressed in both cancerous and non-cancerous breast tissues. Endocrine therapy based on estrogen blockade, by aromatase inhibitors, has been the mainstay of BC treatment in post-menopausal women; however, resistance to hormone therapy is the leading cause of cancer death. An improved understanding of the molecular underpinnings is the key to develop therapeutic strategies for countering the most prevalent hormone receptor positive BCs. Of note, cholesterol is the precursor of all steroid hormones that are synthesized in a variety of tissues and play crucial roles in diverse processes, ranging from organogenesis to homeostasis to carcinogenesis. The rate-limiting step in steroid biosynthesis is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process that is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Advances in genomic and proteomic technologies have revealed a dynamic link between histone deacetylases (HDACs) and StAR, aromatase, and estrogen regulation. We were the first to report that StAR is abundantly expressed, along with large amounts of 17ß-estradiol (E2), in hormone-dependent, but not hormone-independent, BCs, in which StAR was also identified as a novel acetylated protein. Our in-silico analyses of The Cancer Genome Atlas (TCGA) datasets, for StAR and steroidogenic enzyme genes, revealed an inverse correlation between the amplification of the StAR gene and the poor survival of BC patients. Additionally, we reported that a number of HDAC inhibitors, by altering StAR acetylation patterns, repress E2 synthesis in hormone-sensitive BC cells. This review highlights the current understanding of molecular pathogenesis of BCs, especially for luminal subtypes, and their therapeutics, underlining that StAR could serve not only as a prognostic marker, but also as a therapeutic candidate, in the prevention and treatment of this life-threatening disease.

A Case of Valproate-Induced Hyperammonemic Encephalopathy.

A 56-year-old Caucasian male with a history of seizure disorder on long-term prophylaxis with valproate presented with altered mental status, aggressive behavior, decreased oral intake, and frequent myoclonic jerking movements. Electrolyte and other basic metabolic lab testing, liver function testing, and imaging studies were negative for acute abnormalities or infection, though ammonia levels returned markedly elevated, and he also had a macrocytic anemia despite having normal folate and B12 levels. Following discussions with neurology, his valproate was felt to be the inducing factor for his hyperammonemic encephalopathy. After discontinuation of valproate and changing to a new anti-seizure medication, he soon returned to his neurologic baseline. This case report evaluates his presentation and current literature on hyperammonemic encephalopathy induced by valproate.

Genomic Profiling of the Steroidogenic Acute Regulatory Protein in Breast Cancer: In Silico Assessments and a Mechanistic Perspective.

Cancer is a multifactorial condition with aberrant growth of cells. A substantial number of cancers, breast in particular, are hormone sensitive and evolve due to malfunction in the steroidogenic machinery. Breast cancer, one of the most prevalent form of cancers in women, is primarily stimulated by estrogens. Steroid hormones are made from cholesterol, and regulation of steroid/estrogen biosynthesis is essentially influenced by the steroidogenic acute regulatory (StAR) protein. Although the impact of StAR in breast cancer remains a mystery, we recently reported that StAR protein is abundantly expressed in hormone sensitive breast cancer, but not in its non-cancerous counterpart. Herein, we analyzed genomic profiles, hormone receptor expression, mutation, and survival for StAR and steroidogenic enzyme genes in a variety of hormone sensitive cancers. These profiles were specifically assessed in breast cancer, exploiting The Cancer Genome Atlas (TCGA) datasets. Whereas StAR and key steroidogenic enzyme genes evaluated (CYP11A1, HSD3B, CYP17A1, CYP19A1, and HSD17B) were altered to varying levels in these hormone responsive cancers, amplification of the StAR gene was correlated with poor overall survival of patients afflicted with breast cancer. Amplification of the StAR gene and its correlation to survival was also verified in a number of breast cancer studies. Additionally, TCGA breast cancer tumors associated with aberrant high expression of StAR mRNA were found to be an unfavorable risk factor for survival of patients with breast cancer. Further analyses of tumors, nodal status, and metastases of breast cancer tumors expressing StAR mRNA displayed cancer deaths in stage specific manners. The majority of these tumors were found to express estrogen and progesterone receptors, signifying a link between StAR and luminal subtype breast cancer. Collectively, analyses of genomic and molecular profiles of key steroidogenic factors provide novel insights that StAR plays an important role in the biologic behavior and/or pathogenesis of hormone sensitive breast cancer.

Overexpression of the steroidogenic acute regulatory protein in breast cancer: Regulation by histone deacetylase inhibition.

Dysregulation of steroid biosynthesis has been implicated in the pathophysiology of a variety of cancers. One such common malignancy in women is breast cancer that is frequently promoted by estrogen overproduction. All steroid hormones are made from cholesterol, and the rate-limiting step in steroid biosynthesis is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Whereas the involvement of StAR in the regulation steroid hormone biosynthesis is well established, its association to breast cancer remains obscure. Herein, we report that estrogen receptor positive breast cancer cell lines (MCF7, MDA-MB-361, and T-47D) displayed aberrant high expression of the StAR protein, concomitant with 17ß-estradiol (E2) synthesis, when compared their levels with normal mammary epithelial (MCF10A and MCF12F) and triple negative breast cancer (MDA-MB-468, MDA-MB-231, and BT-549) cells. StAR was identified as a novel acetylated protein in MCF7 cells, in which liquid chromatography-tandem mass spectrometry analysis identified seven StAR acetyl lysine residues under basal and in response to histone deacetylase (HDAC) inhibition. A number of HDAC inhibitors were capable of diminishing StAR expression and E2 synthesis in MCF7 cells. The validity of StAR protein acetylation and its correlation to HDAC inhibition mediated steroid synthesis was demonstrated in adrenocortical tumor H295R cells. These findings provide novel insights that StAR protein is abundantly expressed in the most prevalent hormone sensitive breast cancer subtype, wherein inhibition of HDACs altered StAR acetylation patterns and decreased E2 levels, which may have important therapeutic implications in the prevention and treatment of this devastating disease.

Developing counseling skills through pre-recorded videos and role play: a pre- and post-intervention study in a Pakistani medical school.

BACKGROUND: Interactive methods like role play, recorded video scenarios and objective structured clinical exam (OSCE) are being regularly used to teach and assess communication skills of medical students in the western world. In developing countries however, they are still in the preliminary phases of execution in most institutes. Our study was conducted in a naïve under resourced setup to assess the impact of such teaching methodologies on the counseling skills of medical students. METHODS: Fifty four 4th year MBBS students were identified to be evaluated for communication skills by trained facilitators in a pre-intervention OSCE. The same group of students was given a demonstration of ideal skill level by means of videos and role playing sessions in addition to real life interaction with patients during hospital and community rotations. A post-intervention evaluation was carried out six months later through OSCE and direct observation through structured checklist (DOS) in hospital and community settings. The combined and individual performance levels of these students were analyzed. RESULTS: There was a statistically significant difference in the communication skills of students when assessed in the post-intervention OSCE (p = 0.000). Individual post-intervention percentages of study participants displayed improvement as well (n = 45, p = 0.02). No difference was observed between the scores of male and female students when assessed for two specific competencies of antenatal care and breast feeding counseling (p = 0.11). The mean DOS (%) score of 12 randomly selected students was much lower as compared to the post-intervention (%) score but the difference between them was statistically non significant, a result that may have been affected by the small sample size as well as other factors that may come into play in real clinical settings and were not explored in this study (59.41 +/- 7.8 against 82.43 +/- 22.08, p = 0.88). CONCLUSIONS: Videos and role play in combination with community and clinical exposure are effective modes of teaching counseling skills to medical students. They can be successfully utilized even in a limited resource setup, as demonstrated by our trial.