Study of effect of propranolol, atenolol and celiprolol on exercise induced changes in heart rate, blood pressure and peak expiratory flow rate in healthy human volunteers

Background: Beta blockers are known to cause attenuation of sympathetic stimulation mediated increase in cardiovascular parameters. Very few studies are available in Indian set-up comparing these changes between different beta blockers available in market. The objective of the study was to compare efficacy and safety of propranolol, atenolol and celiprolol on heart rare, blood pressure and airway resistance, both at rest and during exercise.Methods: A prospective interventional study was carried out involving 72 healthy volunteers in the clinical pharmacology laboratory. Participants were divided in three groups of 24 each and given single oral doses of propranolol 40 mg, Atenolol 50 mg and celiprolol 40 mg was given to the participants. Exercise given in the form of step ladder test and hand grip dynamometer and effect on the different parameters like HR, SBP, DBP and PEFR were recorded before and immediately after exercise and compared.Results: All the three drugs were effective in attenuating the exercise induced cardiovascular parameters (p 0.05). No adverse effects were reported in the study participants.Conclusions: All the three drugs are effective in attenuating cardiovascular changes after sympathetic stimulation like exercise and there was no significant difference among them

Pharmacoepidemiological profile and appropriateness of drug use in paediatric diarrhoea patients: a cross sectional study in western India

Background: The background of the study was to analyze the prescribing pattern and appropriateness of drug treatment of diarrhoea.Methods: Total 194 pediatric patients with diarrhoea (140 admitted at tertiary care centre and 54 patients attended primary health care centre) were included and their demographic details; disease related parameters, drug treatment and adverse drug reactions were recorded. Appropriateness of drug treatment was analyzed using the WHO and Indian Academy of Pediatrics (IAP) guidelines for management of diarrhoea.Results: Most patients (27.32%) were less than 1 year of age and majority 54.64% were males. Most common presenting symptoms was diarrhoea with dehydration (100%) followed by vomiting (60%), fever (54.29%). Stool cultures were carried out only in 22.86% patients at tertiary health care centre while no investigations were carried out at PHC. Average number of drugs prescribed per patient was 8.25 ± 1.3. All the patients were given fluid replacement therapy. 94.29% and 85.19% patients were prescribed antimicrobials at tertiary centre (THC) and PHC respectively. Most common antibiotic used was cephalosporins (82%) followed by aminoglycosides (48.57%) of patients at THC while ofloxacin (82.60%) and metronidazole (17.40%) were commonly used at PHC.  Analgesic/antipyretic was required in 70.71% and 85.19% of patients at THC and PHC respectively. Comparing with the WHO diarrhoea management guidelines and IAP guidelines, only 8 (14.81%) prescriptions were considered as rational. 2.85% patients developed mucocutaneous rash as ADR.Conclusions: Inappropriate prescribing for diarrhoea is highly prevalent in society. Emphasis on proper diagnosis and treatment, education and availability of locally effective guidelines may help in a better and judicious use of drugs in children

The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution

BACKGROUND:Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP) genes may contribute to this prolonged infection. Only one is expressed at a time, and switching expression from one gene to another occurs by an epigenetic mechanism.RESULTS:The WB Giardia isolate has been sequenced at 10x coverage and assembled into 306 contigs as large as 870 kb in size. We have used this assembly to evaluate the genomic organization and evolution of the vsp repertoire. We have identified 228 complete and 75 partial vsp gene sequences for an estimated repertoire of 270 to 303, making up about 4% of the genome. The vsp gene diversity includes 30 genes containing tandem repeats, and 14 vsp pairs of identical genes present in either head to head or tail to tail configurations (designated as inverted pairs), where the two genes are separated by 2 to 4 kb of non-coding DNA. Interestingly, over half the total vsp repertoire is present in the form of linear gene arrays that can contain up to 10 vsp gene members. Lastly, evidence for recombination within and across minor clades of vsp genes is provided.CONCLUSIONS:The data we present here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

The Profile of Non-Communicable Disease (NCD) research in the Middle East and North Africa (MENA) region: Analyzing the NCD burden, research outputs and international research collaboration.

OBJECTIVES: Despite the rising risk factor exposure and non-communicable disease (NCD) mortality across the Middle East and the North African (MENA) region, public health policy responses have been slow and appear discordant with the social, economic and political circumstances in each country. Good health policy and outcomes are intimately linked to a research-active culture, particularly in NCD. In this study we present the results of a comprehensive analysis of NCD research with particular a focus on cancer, diabetes and cardiovascular disease in 10 key countries that represent a spectrum across MENA between 1991 and 2018. METHODS: The study uses a well validated bibliometric approach to undertake a quantitative analysis of research output in the ten leading countries in biomedical research in the MENA region on the basis of articles and reviews in the Web of Science database. We used filters for each of the three NCDs and biomedical research to identify relevant papers in the WoS. The countries selected for the analyses were based on the volume of research outputs during the period of analysis and stability, included Egypt, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Turkey and the United Arab Emirates. RESULTS: A total of 495,108 biomedical papers were found in 12,341 journals for the ten MENA countries (here we consider Turkey in the context of MENA). For all three NCDs, Turkey's output is consistently the highest. Iran has had considerable growth in research output to occupy second place across all three NCDs. It appears that, relative to their wealth (measured by GDP), some MENA countries, particularly Oman, Qatar, Kuwait and the United Arab Emirates, are substantially under-investing in biomedical research. In terms of investment on particular NCDs, we note the relatively greater commitment on cancer research compared with diabetes or cardiovascular disease in most MENA countries, despite cardiovascular disease causing the greatest health-related burden. When considering the citation impact of research outputs, there have been marked rises in citation scores in Qatar, Lebanon, United Arab Emirates and Oman. However, Turkey, which has the largest biomedical research output in the Middle East has the lowest citation scores overall. The level of intra-regional collaboration in NCD research is highly variable. Saudi Arabia and Egypt are the dominant research collaborators across the MENA region. However, Turkey and Iran, which are amongst the leading research-active countries in the area, show little evidence of collaboration. With respect to international collaboration, the United States and United Kingdom are the dominant research partners across the region followed by Germany and France. CONCLUSION: The increase in research activity in NCDs across the MENA region countries during the time period of analysis may signal both an increasing focus on NCDs which reflects general global trends, and greater investment in research in some countries. However, there are several risks to the sustainability of these improvements that have been identified in particular countries within the region. For example, a lack of suitably trained researchers, low political commitment and poor financial support, and minimal international collaboration which is essential for wider global impact

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report from the Pediatric Nephrology Research Consortium

Introduction Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose. Methods We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients \u3c 21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (\u3e 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. Results Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). Conclusion A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Genetic and Physiologic Dissection of the Vertebrate Cardiac Conduction System

Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS) to coordinate chamber contraction and drive blood efficiently and unidirectionally throughout the organism. Defects in this specialized wiring system can lead to syncope and sudden cardiac death. Thus, a greater understanding of cardiac conduction development may help to prevent these devastating clinical outcomes. Utilizing a cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP)s878, that allows for in vivo optical mapping analysis in intact animals, we identified and analyzed four distinct stages of cardiac conduction development that correspond to cellular and anatomical changes of the developing heart. Additionally, we observed that epigenetic factors, such as hemodynamic flow and contraction, regulate the fast conduction network of this specialized electrical system. To identify novel regulators of the CCS, we designed and performed a new, physiology-based, forward genetic screen and identified for the first time, to our knowledge, 17 conduction-specific mutations. Positional cloning of hobgoblins634 revealed that tcf2, a homeobox transcription factor gene involved in mature onset diabetes of the young and familial glomerulocystic kidney disease, also regulates conduction between the atrium and the ventricle. The combination of the Tg(cmlc2:gCaMP)s878 line/in vivo optical mapping technique and characterization of cardiac conduction mutants provides a novel multidisciplinary approach to further understand the molecular determinants of the vertebrate CCS

Our future: a Lancet commission on adolescent health and wellbeing.

Unprecedented global forces are shaping the health and wellbeing of the largest generation of 10 to 24 year olds in human history. Population mobility, global communications, economic development, and the sustainability of ecosystems are setting the future course for this generation and, in turn, humankind. At the same time, we have come to new understandings of adolescence as a critical phase in life for achieving human potential. Adolescence is characterised by dynamic brain development in which the interaction with the social environment shapes the capabilities an individual takes forward into adult life.3 During adolescence, an individual acquires the physical, cognitive, emotional, social, and economic resources that are the foundation for later life health and wellbeing. These same resources define trajectories into the next generation. Investments in adolescent health and wellbeing bring benefits today, for decades to come, and for the next generation. Better childhood health and nutrition, extensions to education, delays in family formation, and new technologies offer the possibility of this being the healthiest generation of adolescents ever. But these are also the ages when new and different health problems related to the onset of sexual activity, emotional control, and behaviour typically emerge. Global trends include those promoting unhealthy lifestyles and commodities, the crisis of youth unemployment, less family stability, environmental degradation, armed conflict, and mass migration, all of which pose major threats to adolescent health and wellbeing. Adolescents and young adults have until recently been overlooked in global health and social policy, one reason why they have had fewer health gains with economic development than other age groups. The UN Secretary-General's Global Strategy for Women's, Children's and Adolescents' Health initiated, in September, 2015, presents an outstanding opportunity for investment in adolescent health and wellbeing. However, because of limits to resources and technical capacities at both the national and the global level, effective response has many challenges. The question of where to make the most effective investments is now pressing for the international development community. This Commission outlines the opportunities and challenges for investment at both country and global levels (panel 1)