Patients' knowledge, attitudes, behaviour and health care experiences on the prevention, detection, management and control of hypertension in Colombia: a qualitative study.

Hypertension is a leading cause of premature death worldwide and the most important modifiable risk factor for cardiovascular disease. Effective screening programs, communication with patients, regular monitoring, and adherence to treatment are essential to successful management but may be challenging in health systems facing resource constraints. This qualitative study explored patients' knowledge, attitudes, behaviour and health care seeking experiences in relation to detection, treatment and control of hypertension in Colombia. We conducted in-depth interviews and focus group discussions with 26 individuals with hypertension and 4 family members in two regions. Few participants were aware of ways to prevent high blood pressure. Once diagnosed, most reported taking medication but had little information about their condition and had a poor understanding of their treatment regime. The desire for good communication and a trusting relationship with the doctor emerged as key themes in promoting adherence to medication and regular attendance at medical appointments. Barriers to accessing treatment included co-payments for medication; costs of transport to health care facilities; unavailability of drugs; and poor access to specialist care. Some patients overcame these barriers with support from social networks, family members and neighbours. However, those who lacked such support, experienced loneliness and struggled to access health care services. The health insurance scheme was frequently described as administratively confusing and those accessing the state subsidized system believed that the treatment was inferior to that provided under the compulsory contributory system. Measures that should be addressed to improve hypertension management in Colombia include better communication between health care professionals and patients, measures to improve understanding of the importance of adherence to treatment, reduction of co-payments and transport costs, and easier access to care, especially in rural areas

Fitness Changes in Adolescent Girls Following In-School Combined Aerobic and Resistance Exercise: Interaction With Birthweight.

Purpose: To assess the efficacy of a supervised in-school combined resistance and aerobic training program in adolescent girls and investigate whether responses differ according to birthweight. Methods: Participants (girls aged 13–17 y) were randomized either to an intervention replacing physical education (PE) classes with 2 × 60-minute training sessions per week (n = 58) or to a control group that continued to attend 2 × 60 minutes per week of curriculum PE (n = 41). We measured muscular fitness (handgrip, standing long jump, and sit-ups), cardiorespiratory fitness (20-m shuttle run), skinfolds, and lean body mass preintervention and postintervention and determined effect size (Hedge’s g) differences between changes in these measures. We also compared changes within lower (<3000 g) and normal birthweight intervention and PE control subgroups. Results: The intervention group showed greater improvements in all the fitness measures and lean body mass (g = 0.22–0.48) and lower skinfold increases (g = 0.41) than PE controls. Within the intervention group, improvements in all fitness measures were larger in lower birthweight (g = 0.53–0.94) than in normal birthweight girls (g = 0.02–0.39). Conclusion: Replacing curriculum PE with supervised training improved muscular and cardiorespiratory fitness and body composition outcomes in adolescent females. Our findings suggest an enhanced adaptive response to training in participants with lower birthweight which warrants further investigation

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study.

BACKGROUND: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated. OBJECTIVE: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels. METHODS/DESIGN: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated. SIGNIFICANCE: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension

The SIMAC study: A randomized controlled trial to compare the effects of resistance training and aerobic training on the fitness and body composition of Colombian adolescents.

The aim of this study was to evaluate the impact on muscle strength, aerobic fitness and body composition, of replacing the physical education (PE) class of Colombian adolescents with resistance or aerobic training. 120 tanner stage 3 adolescents attending a state school were randomized to resistance training, aerobic training, or a control group who continued to attend a weekly 2- hour PE class for 16 weeks. The resistance training and aerobic training groups participated in twice weekly supervised after-school exercise sessions of < 1 hour instead of their PE class. Sum of skinfolds, lean body mass (bioelectrical impedance analysis), muscular strength (6 repetition maximum (RM)) bench press, lateral pulldown and leg press) and estimated cardiorespiratory fitness (multistage 20 meter shuttle run) were assessed at pre and post intervention. Complete data were available for n = 40 of the resistance training group, n = 40 of the aerobic training group and n = 30 PE (controls). Resistance training attenuated increases in sum of skinfolds compared with controls (d = 0.27, [0.09-0.36]). We found no significant effect on lean body mass. Resistance training produced a positive effect on muscle strength compared with both controls (d = 0.66 [.49-.86]) and aerobic training (d = 0.55[0.28-0.67]). There was a positive effect of resistance training on cardiorespiratory fitness compared with controls (d = 0.04 [-0.10-0.12]) but not compared with aerobic training (d = 0.24 [0.10-0.36]). Replacing a 2-hour PE class with two 1 hour resistance training sessions attenuated gains in subcutaneous adiposity, and enhanced muscle strength and aerobic fitness development in Colombian youth, based on a median attendance of approximately 1 session a week. Further research to assess whether adequate stimuli for the development of muscular fitness exists within current physical education provision is warranted

Two specific populations of GABAergic neurons originating from the medial and the caudal ganglionic eminences aid in proper navigation of callosal axons.

The corpus callosum (CC) plays a crucial role in interhemispheric communication. It has been shown that CC formation relies on the guidepost cells located in the midline region that include glutamatergic and GABAergic neurons as well as glial cells. However, the origin of these guidepost GABAergic neurons and their precise function in callosal axon pathfinding remain to be investigated. Here, we show that two distinct GABAergic neuronal subpopulations converge toward the midline prior to the arrival of callosal axons. Using in vivo and ex vivo fate mapping we show that CC GABAergic neurons originate in the caudal and medial ganglionic eminences (CGE and MGE) but not in the lateral ganglionic eminence (LGE). Time lapse imaging on organotypic slices and in vivo analyses further revealed that CC GABAergic neurons contribute to the normal navigation of callosal axons. The use of Nkx2.1 knockout (KO) mice confirmed a role of these neurons in the maintenance of proper behavior of callosal axons while growing through the CC. Indeed, using in vitro transplantation assays, we demonstrated that both MGE- and CGE-derived GABAergic neurons exert an attractive activity on callosal axons. Furthermore, by combining a sensitive RT-PCR technique with in situ hybridization, we demonstrate that CC neurons express multiple short and long range guidance cues. This study strongly suggests that MGE- and CGE-derived interneurons may guide CC axons by multiple guidance mechanisms and signaling pathways. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 647-672, 2013

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Rapid changes in gene expression: DNA determinants of promoter regulation by the concentration of the transcription initiating NTP in Bacillus subtilis

In bacteria, rapid changes in gene expression can be achieved by affecting the activity of RNA polymerase with small molecule effectors during transcription initiation. An important small molecule effector is the initiating nucleoside triphosphate (iNTP). At some promoters, an increasing iNTP concentration stimulates promoter activity, while a decreasing concentration has the opposite effect. Ribosomal RNA (rRNA) promoters from Gram-positive Bacillus subtilis are regulated by the concentration of their iNTP. Yet, the sequences of these promoters do not emulate the sequence characteristics of [iNTP]-regulated rRNA promoters of Gram-negative Escherichia coli. Here, we identified the 3′-promoter region, corresponding to the transcription bubble, as key for B. subtilis rRNA promoter regulation via the concentration of the iNTP. Within this region, the conserved −5T (3 bp downstream from the −10 hexamer) is required for this regulation. Moreover, we identified a second class of [iNTP]-regulated promoters in B. subtilis where the sequence determinants are not limited to the transcription bubble region. Overall, it seems that various sequence combinations can result in promoter regulation by [iNTP] in B. subtilis. Finally, this study demonstrates how the same type of regulation can be achieved with strikingly different promoter sequences in phylogenetically distant species