Outcomes of Hypospadias Repair Based on Surgical Techniques: A 4-Year Retrospective Study.

Purpose: This study aimed to report the outcomes of hypospadias repair performed at a tertiary-level hospital during 2018 to 2021. Methods: A retrospective chart review of 119 patients was performed. Results: The most frequent coronal hypospadias cases were distal. However, the most common scrotal hypospadias cases were proximal. The average age at the time of the first surgery was 2.4 years (standard deviation, ±2.3 years). The tubularised incised plate technique was performed for 57 of these 119 patients. Urethral fistula was the most common complication associated with distal and proximal cases (23.96% and 30.43%, respectively). No significant correlation was observed between any complication and the surgical technique. Based on the logistic regression model, the duration of urethral stenting was statistically significant (p=0.025), indicating that a urinary catheter duration of more than 5 days resulted in a 2.9-times increased risk of postoperative urethral fistula. Conclusion: Prolonged urethral stenting for more than 5 days may result in subsequent urethral fistula development. Neither the severity of hypospadias nor the surgical technique seems to affect postoperative complications.

Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.

Impaired cardiac structure and systolic function in athletes using supra-physiological doses of anabolic androgenic steroids.

OBJECTIVES: Athletes are increasingly using supra-physiological doses of anabolic androgenic steroids without weighing health side effects. This study aims to conjointly evaluate the effect of supraphysiological doses of anabolic androgenic steroids on global cardiovascular structure and functional capacity. DESIGN: Cross-sectional study. METHODS: 92 males enrolled in the study, including 18 sedentary subjects, 26 anabolic androgenic steroid non-user athletes, and 48 anabolic androgenic steroid-user athletes. Two-dimensional echocardiography was done to evaluate the cardiovascular structure and function. RESULTS: Anabolic androgenic steroid-users presented increased cardiac remodeling of the left ventricle and left atrium compared to control groups (p < 0.001). Anabolic androgenic steroid-users showed increased left ventricular mass/body surface area versus control groups (p < 0.001), with 28 steroid-users (58.3 %) having cardiac remodeling, which is more than control groups (p < 0.001). Anabolic androgenic steroid-users presented lower diastolic function (E and E/A) compared to non-users (p = 0.003 and <0.001, respectively). Ejection fraction was decreased among anabolic androgenic steroid-users versus the sedentary group only (p = 0.020), while anabolic androgenic steroid-users presented reduced global longitudinal strain of 15.43 % compared to both control groups (p < 0.001). Moreover, anabolic androgenic steroid-users experienced more tricuspid valve regurgitation (p = 0.001). CONCLUSIONS: Anabolic androgenic steroid consumption is associated with global cardiac remodeling with increased dimensions of the left ventricle, and atrium. Anabolic androgenic steroid-users present left ventricular hypertrophy with reduced subclinical systolic function. Moreover, anabolic androgenic steroid consumption is correlated with valve regurgitation and dilation of the sino-tubular junction.

Chronic anabolic androgenic steroid administration reduces global longitudinal strain among off-cycle bodybuilders.

BACKGROUND: Supra-physiologic doses of anabolic androgenic steroids (AAS) lead to multiple cardiovascular complications. The long-term clinical effect of AAS overuse on cardiac structure and function, which persists during off-cycle periods, remains unclear. METHODS: A total of 15 sedentary subjects and 79 bodybuilders (26 AAS non-users and 53 AAS-users), matched for age and male gender, were assessed in a cross-sectional design for echocardiography measures. AAS-users were included during an off-cycle phase, abstained from AAS for at least 1 month. 2D standard M-mode and speckle tracking echocardiography were used to measure cardiac dimensions and functions. RESULTS: Inter-ventricular septum and posterior wall thickness were significantly higher among chronic off-cycle AAS-users compared to AAS non-users and sedentary group. Off-cycle AAS-users showed lower E/A ratio of the diastolic function. Left ventricular systolic function was not affected in terms of ejection fraction, but significant subclinical systolic dysfunction, assessed by GLS, was observed for chronic off-cycle AAS-users compared to AAS non-users (GLS = -16.8% vs. -18.5%, respectively; p = 0.001). Diameter of left atrium and right ventricle were significantly enlarged among off-cycle AAS-user bodybuilders (p = 0.002 and 0.040). TAPSE and RV S', and cardiac vasculature of aorta were comparable in all groups. CONCLUSIONS: This study demonstrates that during off-cycle phase, AAS-users show long-term impaired GLS, even after considerable AAS abstain, despite normal LVEF. It highlights the importance of following GLS to predict hypertrophy and heart failure events, and not relying on LVEF alone. In addition, the hypertrophic effect of chronic AAS consumption is transitional during AAS washout periods.

Antimesenteric sleeve tapering enteroplasty with end-to-end anastomosis versus primary end-to-side anastomosis for the management of jejunal/ileal atresia.

BACKGROUND/OBJECTIVE: Small bowel atresia commonly causes neonatal intestinal obstructions. Technical problems are associated with the surgical management of atresia using primary end-to-end anastomosis. Furthermore, the significantly dilated proximal loop may be associated with the stasis of intestinal fluid, thus increasing pressure on the anastomosis and prolonging fasting time before initiation of oral intake. This study aimed to perform antimesenteric tapering of the proximal loop using a linear stapler to reduce its diameter and facilitate anastomosis with the distal loop. METHODS: This retrospective study included 57 neonates diagnosed with jejunoileal atresia. They were categorised into two groups: Group A (n = 29), which included neonates treated using antimesenteric sleeve enteroplasty tapering using a linear stapler and Group B (n = 28), which included neonates treated at the primary end of the proximal loop to the side of the distal loop anastomosis. RESULTS: The mean operative time was 122.5 min in group A vs. 118 min in group B, and the mean duration to reach full oral intake was 17 days in group A vs. 20.2 days in group B (p = 0.03). The mean length of hospital stay was 25 and 35 days in groups A and B, respectively (p = 0.042). CONCLUSION: Tapering the proximal dilated bowel loop to achieve anastomosis with the distal loop improved the transient time, reduced stasis and its associated translocation and colonisation, and allowed for early initiation and maintenance of oral intake. All these parameters shortened the overall length of hospital stay.

Peri-Kasai portoenterostomy sutures anchoring the jejunal loop to Glisson capsule: A novel modification to reduce the incidence of cholangitis.

BACKGROUND: Kasai portoenterostomy (KPE) is the standard surgical management for biliary atresia (BA). To improve the outcome these infants were operated on within the first two months of life. The success of the procedure is reflected by clearance of jaundice and either absence or occurrence of fewer attacks of cholangitis. The failure of the procedure indicates liver transplantation (LT). OBJECTIVE: to reduce the incidence of the recurrent attacks of cholangitis by peri-KPE sutures anchoring the jejunal loop to the Glisson capsule. METHODS: It is a retrospective study that included 45 infants diagnosed with BA and who were operated on at an age younger than 60 days. They were categorized into two groups, Group A (n = 23) included infants treated with the classic KPE, and Group B (n = 22) included infants treated in the same way plus peri KPE sutures anchoring the jejunal loop to the Glisson capsule. RESULTS: The mean operative time in Group A was 149.3 min versus 164.8 min in Group B (p-value 0.039). The mean level of bilirubin was 2.2 versus 2.1 in Group A and Group B respectively at two years follow up. The total attacks of cholangitis per patient were significantly lower in Group B than in Group A (cutoff value = 3), which was reflected by the significant reduction of the incidence of LT in Group B. CONCLUSION: peri KPE sutures anchoring the jejunal loop to the Glisson capsule significantly reduced the incidence of recurrent attacks of cholangitis and subsequently decreased the requirement of LT on the short-term follow-up.

Non-adherence to antihypertensive medications in Lebanese adults hospitalized for hypertensive urgency and its cost.

BACKGROUND: Drug non-adherence is assumed to play an important role in development of hypertensive urgency, which is a common health problem resulting in frequent emergency department admissions and thus increased healthcare spending wastage. The objective of this study is to assess the rate of non-adherence to antihypertensives and to evaluate influencing factors predicting this behavior in Lebanese hypertensive adults. In addition, this study aim to estimate the cost of hospitalization for hypertensive urgency covered by the Ministry of Public Health in patients' non-adherent to their antihypertensives. METHODS: A multi-methods approach is used comprising a cross-sectional study, additionally to an observational, retrospective, cost of illness study. A cross-sectional questionnaire based study is conducted from May to Dec, 2019 to address the study objective. Using the Ministry of Public Health hospitalization data during 2019, the cost of hospitalization for hypertensive urgency is assessed. Multivariable analysis is performed to calculate the adjusted odd ratios by fitting a logistic regression model. RESULTS: The cross-sectional study includes 494 participants and shows that 43.0% of patients hospitalized and covered by the Ministry of Public Health are non-adherent. The univariate regression model shows that adherence to antihypertensive medications is significantly associated with age (p-value = 0.005) and follow-up visits (p-value = 0.046). The odds of adherence for participants earning more than USD 2000 was 3.27 times that for those who earn less than USD 1000 (p = 0.026). The estimated cost of hospitalization for non-adherent patients is USD 452,353 in 2019. CONCLUSION: Non-adherence associated hospitalization costs represents a financial burden to Lebanese health system.

LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response.

Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. Given the capacity of UM171a to trigger APC-like function in MSCs, and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1), we explored whether the direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. The treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements, including pattern recognition receptors (PRRs), Type-I interferon (IFN), and IFN-stimulated genes (ISGs). The net outcome culminates in the enhanced expression of H2-Kb, and an increased stability of the cell surface peptide: MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently, and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines.

Hybrid Mathieu Urethroplasty vs. Tubularized Incised Plate Urethroplasty for the Management of Distal Penile Hypospadias With a Small Glans.

Introduction: Distal hypospadias is a common anomaly. Different surgical techniques have evolved through the years to manage this anomaly. Several factors may affect the prognosis. One of them is glans size. We compared the hybrid Mathieu urethroplasty (HMU) and the tubularized incised plate urethroplasty (TIPU) for the management of distal hypospadias with a small glans. Methods: Sixty-eight patients with distal hypospadias were included and categorized into two groups. Group A (n = 33) and group B (n = 35) patients were treated by HMU and TIPU, respectively. All patients had a small glans. In group A, the patients underwent Mathieu urethroplasty plus a deep incision of the urethral plate. In group B, the patients underwent TIPU. Urethral stents were used in all cases. Hypospadias objective score evaluation (HOSE) was used to assess the results. Results: Urethrocutaneous fistulae developed in two cases in group A and six cases in group B. Meatal stenosis was significantly lower (one case in group A vs. eight cases in group B). Glanular dehiscence occurred in two cases in group A and five cases in group B. The small glans strongly correlated with the development of both urethrocutaneous fistulae and meatal stenosis where the odd ratios were 3.500 (1.383-7.879) and 9.481 (1.114-12.669), respectively. Conclusion: Both techniques showed efficacy during management of patients with a small glans. HMU had better outcomes, shorter duration of stent and lesser incidence of complications than TIPU. Small glans was significantly related to urethrocutaneous fistulae and meatal stenosis in group B.

What Role do Mitochondria Have in Diastolic Dysfunction? Implications for Diabetic Cardiomyopathy and Heart Failure With Preserved Ejection Function.

ABSTRACT: Diastolic dysfunction is common to both diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). Although commonly attributed to increased fibrosis, alterations in mitochondrial function and associated Ca2+ handling may contribute to impaired cardiac function. With mitochondrial dysfunction, increased reactive oxygen species (ROS), inflammation, and decreased adenosine triphosphate/adenosine diphosphate ratio may lead to increased extracellular matrix and diminished contractile relaxation. In this article, we discuss recent research implicating deficient mitochondria-associated endoplasmic reticulum membranes (MAMs) as it relates to impaired metabolic function and what role that may have in diastolic dysfunction in diabetic cardiomyopathy. The contribution of mitochondrial dysfunction to diastolic dysfunction in HFpEF is less established, but equally credible based on preclinical studies. However, there are notable differences between diabetic cardiomyopathy and HFpEF. Recent evidence implicates impaired endoplasmic reticulum signaling, in particular the unfolded protein response (UPR), in the pathogenesis of HFpEF. With HFpEF, enhanced pressure on the mitochondrial "gas pedal" because of increased cytosolic Ca2+ may perturb mitochondrial homeostasis. For diabetic cardiomyopathy and HFpEF, a better understanding of how altered cellular ion and redox status affect mitochondrial function is needed. Finally, we discuss the implications that mitochondrial dysfunction may have in devising novel therapeutic strategies for diabetic cardiomyopathy and HFpEF.

UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been extensively used in the clinic due to their exquisite tissue repair capacity. However, they also hold promise in the field of cellular vaccination as they can behave as conditional antigen presenting cells in response to interferon (IFN)-gamma treatment under a specific treatment regimen. This suggests that the immune function of MSCs can be pharmacologically modulated. Given the capacity of the agonist pyrimido-indole derivative UM171a to trigger the expression of various antigen presentation-related genes in human hematopoietic progenitor cells, we explored the potential use of UM171a as a means to pharmacologically instill and/or promote antigen presentation by MSCs. METHODS: Besides completing a series of flow-cytometry-based phenotypic analyses, several functional antigen presentation assays were conducted using the SIINFEKL-specific T-cell clone B3Z. Anti-oxidants and electron transport chain inhibitors were also used to decipher UM171a's mode of action in MSCs. Finally, the potency of UM171a-treated MSCs was evaluated in the context of therapeutic vaccination using immunocompetent C57BL/6 mice with pre-established syngeneic EG.7T-cell lymphoma. RESULTS: Treatment of MSCs with UM171a triggered potent increase in H2-Kb cell surface levels along with the acquisition of antigen cross-presentation abilities. Mechanistically, such effects occurred in response to UM171a-mediated production of mitochondrial-derived reactive oxygen species as their neutralization using anti-oxidants or Antimycin-A mitigated MSCs' ability to cross-present antigens. Processing and presentation of the immunogenic ovalbumin-derived SIINFEKL peptide was caused by de novo expression of the Psmb8 gene in response to UM171a-triggered oxidative stress. When evaluated for their anti-tumoral properties in the context of therapeutic vaccination, UM171a-treated MSC administration to immunocompetent mice with pre-established T-cell lymphoma controlled tumor growth resulting in 40% survival without the need of additional supportive therapy and/or standard-of-care. CONCLUSIONS: Altogether, our findings reveal a new immune-related function for UM171a and clearly allude to a direct link between UM171a-mediated ROS induction and antigen cross-presentation by MSCs. The fact that UM171a treatment modulates MSCs to become antigen-presenting cells without the use of IFN-gamma opens-up a new line of investigation to search for additional agents capable of converting immune-suppressive MSCs to a cellular tool easily adaptable to vaccination.

Delayed vs. early enteral feeding after repair of congenital recto-vestibular fistula: The effect on perineal wound healing.

Introduction: congenital Recto vestibular fistula represents the commonest type of anorectal malformation in females. The treatment of this anomaly is mainly approached either through anterior or posterior sagittal ano-rectoplasty approach. Several perioperative factors may affect the outcome. One of major postoperative complications is the occurrence of wound infection. We aimed to study the effect of delayed vs. early enteral feeding on the occurrence of perineal wound infection (PWI) after repair of congenital recto vestibular fistula. Patients and methods: Fifty-five infants with recto-vestibular fistula were included. They were managed by single stage anterior sagittal anorectoplasty (ASARP) at an age ≥3 months. Groups A and B included infants who started oral intake on the 6th and 2nd postoperative days respectively. Group A infants were kept on peripheral parenteral nutrition (PPN) during the fasting period. Results: Superficial wound infection occurred in three cases in group A while it developed in seven cases in group B. Deep perineal infection occurred in two and five cases in group A and group B respectively. The mean hospital stay was 8 days in group A vs. 13 days in group B when PWI developed. Conclusion: Delayed enteral feeding with PPN keeps the perineal wound less contaminated with stool. This promoted proper and fast healing with lower incidence of PWI. Also, PPN compensates the catabolic effects of both surgical trauma and fasting during the postoperative period and ensures maintenance of normal levels of essential nutrients that allow for proper healing.

Impact of Fasting on Cardiovascular Outcomes in Patients With Hypertension.

ABSTRACT: Fasting has been frequently practiced for religious or medical purposes worldwide. However, limited literature assesses the impact of different fasting patterns on the physiologic and cardiac-related parameters in patients with hypertension. This review aims to examine the effect of fasting on cardiovascular outcomes in hypertensive patients. Medline, Embase, and Cochrane library were systematically screened until March 2021 for observational prospective cohorts investigating the effect of fasting on cardiovascular outcomes. Articles were assessed by searching for hypertension and fasting, both as Medical Subject Headings (MeSH) terms and text words. The review included studies assessing Ramadan, intermittent, and water-only fasting. Water-only fasting reduces body weight, blood pressure, and lipolytic activity of fasting hypertensive patients without affecting average heart rate. Ramadan fasting enhances lipid profile, although it shows conflicting results for body weight, blood pressure, and heart rate variability. Considering the limited studies in this field, further research should be conducted to support the clinical impact of fasting on the cardiovascular health of patients with hypertension.

Survey investigating the knowledge and awareness of payers and patient advocacy groups about the health technology assessment process in Lebanon.

The survey aims to assess the knowledge and awareness of Reimbursement Bodies (RBs) and Patient Advocacy Groups (PAGs) in Lebanon and the possible involvement of patients in the health technology assessment (HTA) process in the absence of a well-established HTA structure and to identify the actions to be taken at this level. Structured questionnaires were administered to eleven key participants from both RBs and PAGs. The survey utilized two different questionnaires, each composed of two open-ended questions and ten close-ended questions. RBs recognized the need for clinical and technical guidelines to optimize the HTA process, whereas PAGs stated that they are familiar with the current assessment and reimbursement process. A lack of interaction between the payers and the PAGs was reported mainly due to the absence of laws that involve patients in the assessment process. All the payers and three out of five of PAGs encouraged the involvement of PAGs in the assessment process. They reported that patients require support, education, and training to be efficiently involved. A short-term plan for involving patients in the assessment process can be implemented in light of RBs' and PAGs' openness for such involvement. In the long run, the collaboration between both parties needs to be more formalized and structured. Education and training programs are to be suggested for other PAGs. The institutionalization of an HTA body that unifies all the fragmented RBs, including a patient's representation to optimize the reimbursement process and to engage patients, is recommended.

Impact of Ramadan Intermittent Fasting on the Heart Rate Variability and Cardiovascular Parameters of Patients with Controlled Hypertension.

BACKGROUND: Conflicting results are reported on the effect of Ramadan fasting on the cardiovascular health of patients with hypertension, a highly prevalent cardiovascular disease risk factor. This research aimed to evaluate the impact of fasting on cardiac health and heart rate variability (as a measure of cardiac stress) of hypertensive patients. METHODS: Patients with controlled hypertension were followed in a prospective cohort during and after Ramadan. Lipid panel and blood glucose were measured at the end of each phase. Blood pressure and heart rate variability were monitored in the morning, afternoon, and evening of each follow-up day. RESULTS: The study included 58 subjects (mean age: 54 ± 11.5 years, 52% male). Fasting did not affect body composition, lipid panel parameters, and blood pressure of hypertensive subjects; males only presented lower body weight and hip circumference during Ramadan. Blood glucose was significantly higher during Ramadan. Fasting significantly increased HRV during the afternoon period. CONCLUSIONS: Ramadan intermittent fasting reduces cardiac stress among hypertensive patients controlled by and adherent to hypertensive medication, without affecting their hypertensive state.

Patients' knowledge and awareness about patient support programs: a cross-sectional study on Lebanese adults with chronic diseases.

OBJECTIVE: Patient Support Programs (PSPs) have become a trend among pharmaceutical companies and a standard service offering to patients. The objective of the present study is to describe the status of PSPs in Lebanon and to assess the extent of knowledge and awareness among Lebanese patients about the PSPs. METHODS: A cross-sectional study was conducted between April and July 2017. A convenient sample of patients was randomly selected from outpatient clinics at four hospitals within the Greater Beirut Area. A questionnaire was used to address the study objective. Bivariate analysis was performed using the Chi-square test. Data were analyzed by using SPSS version 23. RESULTS: Out of 385 patients who participated in the study, 45.45 percent were aged between 46 and 66 years. None of them indicated that they were enrolled in a PSP, and only 13 percent of the respondents were aware of the existence of such a program. In terms of adherence habits, 55.6 percent of the patients self-reported that they do not skip any dose of their medication and consume their medication as prescribed by their healthcare providers. The main reason for nonadherence reported by the majority of nonadherent participants 144 (84.2%) was simple forgetfulness. CONCLUSIONS: There is a severe lack of awareness of PSPs in Lebanon. Given the important role that PSPs play in creating value for patients-in terms of healthcare follow-up practices, improved adherence habits, and cost savings-there should be a more substantial effort by pharmaceutical companies to expand and promote their PSPs in the Lebanese market.

Reduced reticulum-mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy.

Type 2 diabetic cardiomyopathy features Ca2+ signaling abnormalities, notably an altered mitochondrial Ca2+ handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca2+ homeostasis, the reticulum-mitochondrial Ca2+ coupling, and/or the mitochondrial Ca2+ entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum-mitochondria interface revealed tighter interactions not compatible with Ca2+ transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca2+ sensors were performed to measure Ca2+ fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R-VDAC interaction and a reduced IP3-stimulated Ca2+ transfer to mitochondria, with no changes in reticular Ca2+ level, cytosolic Ca2+ transients, and mitochondrial Ca2+ uniporter function. Disruption of organelle Ca2+ exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca2+ transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum-mitochondria Ca2+ miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca2+ dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy.

Factors Associated with Antihypertensive Medication Non-Adherence: A Cross-Sectional Study Among Lebanese Hypertensive Adults.

BACKGROUND: Poor adherence to antihypertensives is associated with negative outcome of the disease as well as loss of health-care resources. Addressing the epidemic of poor adherence requires identifying factors associated with this behaviour. The aim of this study is to describe adherence to antihypertensive medication among Lebanese hypertensive patients and to evaluate the association between socio-economic, patient- and conditions-related factors and non-adherence. METHODS: A cross-sectional study was carried out on adherence to antihypertensive medications covering all governorates of Lebanon. This study was conducted between February 2018 and January 2019 on a random sample of 1497 hypertensive patients. A face-to-face questionnaire was used to assess adherence to antihypertensive medication and its determinants according to the five World Health Organization (WHO) main categories. Logistic regression analysis was performed to test the adjusted association between the multiple exposure factors, and drug adherence data were collected by trained interviewers. RESULTS: Adherence to antihypertensive medications was reported by 1253 (83.7%) of the patients. After multivariate analysis, patients who tried to control their stress level (OR = 0.77, 95% CI [0.38-0.95]), those who had normal BP readings (OR =0.49, 95% CI [0.18-0.97]), and those who believed in the effectiveness of their treatment (OR = 0.31, 95% CI [0.14-0.76]) had a significantly lower chance to exhibit non-adherence to their treatment. However, older patients (OR= 1.87, 95% CI [1.23-2.21]), divorced/separated patients (OR= 2.14, 95% CI [1.31-5.48]), married (OR=1.96, 95% CI [1.27-3.90]), widowed (OR=2.11, 95% CI [1.62-6.50]), obese patients (OR = 1.76, 95% CI [1.21-1.94]), and patients who smoked hookah and cigarettes (OR = 2.62, 95% CI [1.17-6.76]) were more likely to exhibit non-adherence. CONCLUSION: Our study highlights the influence of factors such as old age, marital status, BMI and high level of emotional stress on non-adherence to medication in hypertensive patients. These determinants should be incorporated into adherence improving strategies.