Association of Adolescent Hypertension With Future End-stage Renal Disease.

Importance: Hypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned. Objective: To investigate the association between hypertension and future ESRD in otherwise healthy adolescents. Design, Setting, and Participants: This retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018. Main Outcomes and Measures: End-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014. Results: The cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24). Conclusions and Relevance: Hypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.

Self-learning of point-of-care cardiac ultrasound - Can medical students teach themselves?

BACKGROUND: Point-of-care ultrasonography (PoCUS) is a rapidly evolving discipline that aims to train non-cardiologists, non-radiologists clinicians in performing bedside ultrasound to guide clinical decision. Training of PoCUS is challenging, time-consuming and requires large amount of resources. The objective of our study was to evaluate if this training process can be simplified by allowing medical students self-train themselves with a web-based cardiac ultrasound software. METHODS: A prospective, single blinded, cohort study, comparing performance of 29 medical students in performing a six-minutes cardiac ultrasound exam. Students were divided into two groups: self-learning group, using a combination of E-learning software and self-practice using pocket ultrasound device compared to formal, frontal cardiac ultrasound course. RESULTS: All 29 students completed their designated courses and performed the six-minutes exam: 20 students participated in the frontal cardiac ultrasound course and 9 completed the self-learning course. The median (Q1,Q3) test score for the self-learning group was higher than the frontal course group score, 18 (15,19) versus 15 (12,19.5), respectively. Nevertheless, no statistically significant difference was found between the two study groups (p = 0.478). All students in the self-learning course group (9/9, 100%) and 16 (16/20, 80%) of students in the frontal ultrasound course group obtained correct alignment of the parasternal long axis view (p = 0.280). CONCLUSIONS: Self-learning students combining E-learning software with self-practice cardiac ultrasound were as good as students who received a validated, bedside, frontal cardiac ultrasound course. Our findings suggest that independent cardiac ultrasound learning, combining utilization of E-learning software and self-practice, is feasible. Self-E- learning of cardiac ultrasound may serve as an important, cost-effective adjunct to heavily resource consuming traditional teaching.

The zinc sensing receptor, ZnR/GPR39, in health and disease.

While zinc has had a well-established structural role for many years, it is only during the last two decades that its role as a signaling molecule has been recognized. Ionic zinc, Zn2+, that is endogenously released during physiological activity acts as a first messenger, triggering the activity of a distinct Zn2+-sensing-receptor, ZnR. The ZnR is a member of the Gq-coupled receptor family, and the molecular moiety mediating its activity is GPR39. In this review, we will discuss the role of the ZnR/GPR39 in mediating Zn2+-dependent signaling in epithelial tissues and in neurons, where Zn2+ homeostasis plays physiological as well as pathological roles. Importantly, ZnR/GPR39 activates signaling that regulates a remarkably wide range of cell functions, including proliferation, differentiation and survival, as well as modulation of ion transport, and thereby, regulation of Na+, H+ and Cl- homeostasis. Moreover, signaling activated by ZnR/GPR39 plays a key role in mediating effects of Zn2+ in health and disease. Thus, ZnR/GPR39 provides a unique target for therapeutically modifying the actions of zinc in a specific and selective manner.

Effective medical leadership in times of emergency: a perspective.

Leadership, and more specifically medical leadership, is an unmeasured potential that has the power to influence every aspect of a person's professional life and its challenges and is more evident in times of emergency. Medical leadership is receiving increasing recognition especially in discussing actions to be taken in times of stress and emergency. We propose a comprehensive conceptual model that examines the elements that build successful medical leadership, especially during emergency scenarios. The model is based on two sets of medical leadership capabilities and skills, while the first set is more relevant to everyday challenges, the second set represents abilities and characteristics that arise mostly during emergencies. The model gathers together the characteristics and abilities of the medical leader based on our unique personal experiences during conflicts, terror, civilian challenges and numerous humanitarian missions. This article suggests a framework for the foundations on which the medical leader's education should be built and describes our perception of how to establish medical leadership, its unique elements and the processes leading to outstanding performance in times of emergency.

Reevaluating the selection process for the Israeli Defense Force's paramedic training program.

BACKGROUND: Selecting candidates for medical training programs is a complicated process aimed at identifying specific personal competencies, in an attempt to minimize attrition and produce better medical providers. The objective of this study was to evaluate the accuracy of the selection process for the Israeli Defense Force's paramedic training program and its ability to predict success measured at different end points. METHODS: Selection process test scores were crossed and measured against three different end points: attrition, national certification test scores, and training program graduation scores. RESULTS: Data were available for 146 candidates. A positive association was detected between lower formulated selection scores and attrition rates (p<0.01). Out of the 11 tests conducted that comprise the final selection score, two had shown significant association with attrition. The calculated score of these specific two tests was found to have similar association with attrition as the formulated selection score. CONCLUSIONS: The current Israeli Defense Force's paramedic-formulated selection score has shown association with attrition; candidates performing poorly throughout the selection process were less likely to complete training. Similar results may be achieved by implementing a more efficient selection process based on fewer tests. Further studies are required to identify the optimal composition for selection processes. Ongoing learning and research form the ground for improvement, not only of trauma medicine but of all aspects of medicine.

Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures.

The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of mZnR/GPR39 enhances inhibitory drive in the hippocampus by upregulating neuronal K(+)/Cl(-) co-transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type (WT) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile mZnR/GPR39 KO hippocampal slices, a phenomenon that can be reproduced in WT tissue by extracellular Zn(2+) chelation. Importantly, kainate-induced synaptic Zn(2+) release enhances surface expression and transport activity of KCC2 in WT, but not mZnR/GPR39 KO hippocampal neurons. Kainate-dependent upregulation of KCC2 requires mZnR/GPR39 activation of the Gαq/phospholipase C/extracellular regulated kinase (ERK1/2) signaling cascade. We suggest that mZnR/GPR39-dependent upregulation of KCC2 activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, mZnR/GPR39 may provide a novel pharmacological target for dampening epileptic seizure activity.

Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis.

Although it is well established that many glutamatergic neurons sequester Zn(2+) within their synaptic vesicles, the physiological significance of synaptic Zn(2+) remains poorly understood. In experiments performed in a Zn(2+)-enriched auditory brainstem nucleus--the dorsal cochlear nucleus--we discovered that synaptic Zn(2+) and GPR39, a putative metabotropic Zn(2+)-sensing receptor (mZnR), are necessary for triggering the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). The postsynaptic production of 2-AG, in turn, inhibits presynaptic probability of neurotransmitter release, thus shaping synaptic strength and short-term synaptic plasticity. Zn(2+)-induced inhibition of transmitter release is absent in mutant mice that lack either vesicular Zn(2+) or the mZnR. Moreover, mass spectrometry measurements of 2-AG levels reveal that Zn(2+)-mediated initiation of 2-AG synthesis is absent in mice lacking the mZnR. We reveal a previously unknown action of synaptic Zn(2+): synaptic Zn(2+) inhibits glutamate release by promoting 2-AG synthesis.

Upregulation of KCC2 activity by zinc-mediated neurotransmission via the mZnR/GPR39 receptor.

Vesicular Zn(2+) regulates postsynaptic neuronal excitability upon its corelease with glutamate. We previously demonstrated that synaptic Zn(2+) acts via a distinct metabotropic zinc-sensing receptor (mZnR) in neurons to trigger Ca(2+) responses in the hippocampus. Here, we show that physiological activation of mZnR signaling induces enhanced K(+)/Cl(-) cotransporter 2 (KCC2) activity and surface expression. As KCC2 is the major Cl(-) outward transporter in neurons, Zn(2+) also triggers a pronounced hyperpolarizing shift in the GABA(A) reversal potential. Mossy fiber stimulation-dependent upregulation of KCC2 activity is eliminated in slices from Zn(2+) transporter 3-deficient animals, which lack synaptic Zn(2+). Importantly, activity-dependent ZnR signaling and subsequent enhancement of KCC2 activity are also absent in slices from mice lacking the G-protein-coupled receptor GPR39, identifying this protein as the functional neuronal mZnR. Our work elucidates a fundamentally important role for synaptically released Zn(2+) acting as a neurotransmitter signal via activation of a mZnR to increase Cl(-) transport, thereby enhancing inhibitory tone in postsynaptic cells.