The effects of biphasic waveform design on post-resuscitation myocardial function

OBJECTIVES: This study examined the effects of biphasic truncated exponential waveform design on survival and post-resuscitation myocardial function after prolonged ventricular fibrillation (VF). BACKGROUND: Biphasic waveforms are more effective than monophasic waveforms for successful defibrillation, but optimization of energy and current levels to minimize post-resuscitation myocardial dysfunction has been largely unexplored. We examined a low-capacitance waveform typical of low-energy application (low-energy biphasic truncated exponential [BTEL]; 100 microF, < or =200 J) and a high-capacitance waveform typical of high-energy application (high-energy biphasic truncated exponential [BTEH]; 200 microF, > or =200 J). METHODS: Four groups of anesthetized 40- to 45-kg pigs were investigated. After 7 min of electrically induced VF, a 15-min resuscitation attempt was made using sequences of up to three defibrillation shocks followed by 1 min of cardiopulmonary resuscitation. Animals were randomized to BTEL at 150 J or 200 J or to BTEH at 200 J or 360 J. RESULTS: Resuscitation was unsuccessful in three of the five animals treated with BTEH at 200 J. All other attempts were successful. Significant therapy effects were observed for survival (p = 0.035), left ventricular ejection fraction (p < 0.001), stroke volume (p < 0.001), fractional area change (p < 0.001), cardiac output (p = 0.044), and mean aortic pressure (p < 0.001). Hemodynamic outcomes were negatively associated with energy and average current but positively associated with peak current. Peak current was the only significant predictor of survival (p < 0.001). CONCLUSIONS: Maximum survival and minimum myocardial dysfunction were observed with the low-capacitance 150-J waveform, which delivered higher peak current while minimizing energy and average current.     

Evidence for the contribution of non-covalent steroid interactions between DNA and topoisomerase in the genotoxicity of steroids

Fifty two steroids and 9 Vitamin D analogs were docked into ten crystallographically-defined DNA dinucleotide sites and two human topoisomerase II ATP binding sites using two computational programs, Autodock and Surflex. It is shown that both steroids and Vitamin D analogs exhibit a propensity for non-covalent intercalative binding to DNA. A higher predicted binding affinity was found, however, for steroids and the ATP binding site of topoisomerase; in fact these drugs exhibited among the highest topo II binding observed in over 1370 docked drugs. These findings along with genotoxicity data from 26 additional steroids not subjected to docking analysis, support a mechanism wherein the long known, but poorly understood, clastogenicity of steroids may be attributable to inhibition of topoisomerase. A “proof of principle” experiment with dexamethasone demonstrated this to be the likely mechanism of clastogenicity of, at least, this steroid. The generality of this proposed mechanism of genotoxicity across the steroids and vitamin-D analogs is discussed.     

G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.     

Perceptions of Barriers and Benefits to Physical Activity Among Outpatients in Psychiatric Rehabilitation

PURPOSE: To explore perceived barriers and benefits to physical activity in people with serious and persistent mental illness (SPMI) who were enrolled in community-based psychiatric rehabilitation. DESIGN AND METHODS: Four focus groups, two for men and two for women, were held with a total of 34 outpatients from two program sites. The investigators used a semistructured interview guide to facilitate the discussions. Audiotapes of the discussions were transcribed and analyzed for concepts and themes. FINDINGS: Significant barriers to physical activity were: mental illness symptoms, medications, weight gain from medications, fear of discrimination, and safety concerns. Being in a psychiatric rehabilitation program offered comfort and belonging, but it also had the effect of leaving activity initiation up to the program staff, which some participants perceived was part of required program compliance. However, participants viewed physical activity positively, and they linked being active to improved mental health. CONCLUSIONS: Outpatients in psychiatric rehabilitation valued physical activity, but mental illness symptoms, medication sedation, weight gain, fear of unsafe conditions, fear of discrimination, and interpretations of program compliance were barriers. Confronting how attitudes and barriers specific to this population can affect activity and reframing program compliance to include the independent initiation of activity as part of improving health might help clients of mental health services to become more active.     

Traumatic coronary artery fistula

We report certain diagnostic and therapeutic problems presented by patients with traumatic coronary arteriovenous or arteriocameral fistulas, based on our experience with one case and our review of cases which have previously been reported in detail.     

Digitalization of routine health information systems: Bangladesh,Indonesia, Pakistan

ObjectiveTo describe a systematic process of transforming paper registers into a digital system optimized to enhance service provision and fulfil reporting requirements.MethodsWe designed a formative study around primary health workers providing reproductive, maternal, newborn and child health services in three countries in Bangladesh, Indonesia and Pakistan. The study ran from November 2014 to June 2018. We developed a prototype digital application after conducting a needs assessment of health workers’ responsibilities, workflows, routine data requirements and service delivery needs. Methods included desk reviews, focus group discussions, in-depth interviews; data mapping of paper registers; observations of health workers; co-design workshops with health workers; and usability testing. Finally, we conducted an observational feasibility assessment to monitor uptake of the application.FindingsResearchers reviewed a total of 17 paper registers across the sites, which we transformed into seven modules within a digital application running on mobile devices. Modules corresponded to the services provided, including household enumeration, antenatal care, family planning, immunization, nutrition and child health. A total of 65 health workers used the modules during the feasibility assessment, and average weekly form submissions ranged from 8 to 234, depending on the health worker and their responsibilities. We also observed variability in the use of modules, requiring consistent monitoring support for health workers.ConclusionLessons learnt from this study shaped key global initiatives and resulted in a software global good. The deployment of digital systems requires well-designed applications, change management and strengthening human resources to realize and sustain health system gains.