Strategies to increase rural maternal utilization of skilled health personnel for childbirth delivery in low- and middle-income countries: a narrative review.

BACKGROUND: Skilled attendance at birth is considered key to accomplishing Sustainable Development Goal (SDG) 3.1 aimed at reducing maternal mortality. Many maternal deaths can be prevented if a woman receives care by skilled health personnel. Maternal utilization of skilled health delivery services in rural areas in low- and middle-income countries is 70% compared to 90% in urban areas. Previous studies have found community-based interventions may increase rural maternal uptake of skilled health delivery services, but evidence is lacking on which strategies are most effective. OBJECTIVE: To review the effectiveness of community-based strategies to increase rural maternal utilization of skilled health personnel for childbirth delivery in low-and middle-income countries. METHODS: We conducted a narrative review. PubMed, CINAHL, Cochrane Library, and PsycINFO databases were searched for articles from database inception through 13 November 2019. Key search terms were pre-determined. Information was extracted on studies meeting our inclusion criteria: cluster and randomized trials, rural setting, reproductive aged women, community engagement, low- and middle-income countries. Studies were considered effective if statistically significant (p < 0.05). A narrative synthesis was conducted. RESULTS: Ten cluster randomized trials out of 5,895 candidate citations met the inclusion criteria. Strategies included home-based visits, women's groups, and combined approaches. Out of the ten articles, only three studies were found to significantly increase maternal uptake of skilled health personnel for delivery, and each used a different strategy. The results are inconclusive as to which strategies are most effective. Limitations of this review include heterogeneity and generalizability of studies. CONCLUSIONS: This research suggests that different strategies may be effective at improving maternal utilization of skilled health personnel for delivery in certain rural settings while ineffective in others. More research is warranted to better understand the context in which strategies may be effective and under what conditions.

Chronic exogenous ketone supplementation blunts the decline of cardiac function in the failing heart.

AIMS: Recent evidence has demonstrated that ketone bodies, particularly ß-hydroxybutyrate (BHB), are beneficial to the failing heart due to their potential as an alternative energy substrate as well as their anti-inflammatory and anti-oxidative properties. Exogenous supplementation of ketones also helps prevent heart failure (HF) development in rodent models, but whether ketones can be used to treat HF remains unexplored. Herein, we investigated whether chronic supplementation of ketones is beneficial for the heart in a mouse model of established HF. METHODS AND RESULTS: To elevate circulating ketone levels, we utilized (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate [ketone ester (KE)]. C57Bl/6N male mice were subjected to transverse aortic constriction (TAC) surgery. After developing HF, mice were treated with either 20% KE or vehicle via drinking water for 2 weeks. In another cohort, mice 3-4 weeks post-TAC received acute intravenous infusions of BHB or saline for 1 h and their cardiac function was measured. 20% KE significantly elevated blood BHB in mice (P < 0.01) without inducing ketoacidosis or altering other metabolic parameters. Mice with overt HF (30-45% ejection fraction) treated with 20% KE displayed significantly elevated circulating ketone levels compared with vehicle-treated mice (P < 0.05). The significant cardiac dysfunction in mice with HF continued to worsen after 2 weeks of vehicle treatment, whereas this decline was absent in KE-treated mice (mean difference 4.7% ejection fraction; P < 0.01). KE treatment also alleviated TAC-induced cardiomyocyte hypertrophy (P < 0.05) and reduced the TAC-induced elevated cardiac periostin (P < 0.05), a marker of activated fibroblasts. Cardiac fibrosis was also significantly reduced with KE treatment in TAC mice (P < 0.01). In another cohort, acute BHB infusion significantly increased the cardiac output of mice with HF (P < 0.05), providing further support that ketone therapy can be used to treat HF. CONCLUSIONS: We show that chronic treatment of exogenous ketones is of benefit to the failing heart and that chronic ketone elevation may be a therapeutic option for HF. Further investigations to elucidate the underlying mechanism(s) are warranted.

Long-term Follow Up of Ileal Ureteral Replacement for Complex Ureteral Strictures: Single Institution Study.

OBJECTIVE: To report our 16-year experience with ileal ureter interposition for complex ureteral stricture. Ureteral reconstruction continues to evolve to include less invasive techniques to successfully manage ureteral stricture. However, long, complex, obliterative and especially radiated ureteral strictures are not amenable to less invasive techniques and may require Ileal ureter interposition. MATERIALS AND METHODS: Retrospective review of a single institution's ureteral reconstruction database was performed. Demographics, operative details, success rate, complication rate, and length of follow-up were noted. Unilateral replacements utilized ileal ureteral interposition. Success rate was defined as no need for further open intervention. RESULTS: Between 2003 and 2019, 188 ureteral reconstructions were performed, of which 46 required ileal ureter interposition. Of these 46 patients, 10 required bilateral reconstruction. Average age was 53 years, 26 (57%) were female. The average stricture length was 9.1 cm (2-20 cm). Stricture etiology included iatrogenic causes (n = 24, 52%), radiation causes (n = 12; 26%), vascular disease (n = 3; 7%), and idiopathic retroperitoneal fibrosis (n = 3; 7%). Forty-three surgeries were performed by open abdominal approach; 3 were performed robotically. The average length of operation was 412 minutes, blood loss 417 mL and LOS was 10 days. At mean follow up of 4.4 years (1-16 years), overall success rate was 83%, with 17% (n = 8) patients requiring subsequent major surgery (5 successful ureteral revision, 3 nephrectomy) and 11 (24%) patients experiencing a major complication. CONCLUSION: In our long-term follow up of over 4 years, ileal ureteral interposition remains a successful option for complex ureteral strictures in properly selected patients.

Abortion in rural Ghana: Cultural norms, knowledge and attitudes.

Using qualitative methodology, semi-structured questionnaires were administered to participants in the Barakese subdistrict of Ghana in order to understand the extent to which men and women have knowledge of family planning services and in what ways cultural norms, practices, and attitudes toward abortion affect the decision to abort. Women in the community pursue abortion using unsafe methods, despite fear of shame, bleeding, infection, or death, as the perceived cost of maintaining the pregnancy is greater. Protective factors that were reported to dissuade women from pursuing unsafe abortion include fear of social disgrace, divine retribution, and death. Women reported the inability to control the timing of their pregnancies, despite harboring knowledge of family planning. Concerned about perceived side effects of modern family planning methods, respondents chose to use fertility awareness methods or to use no contraception. There remains a gap between knowledge of the benefits of and the actual use of family planning methods, leading to unwanted pregnancy and seeking unsafe abortion. Intensified health promotion and education regarding side effects to combat misconceptions related to contraception, as well as expanding alternative contraceptive options to all regions of Ghana, are critical to improve uptake.

Radiographic evaluation of patellar ligament length after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To radiographically compare patellar ligament length (PLL) in dogs undergoing tibial plateau leveling osteotomy (TPLO) for unilateral cranial cruciate ligament rupture at preoperative, postoperative, and follow-up evaluations. ANIMALS: 105 dogs that underwent TPLO for unilateral cranial cruciate ligament rupture at a referral veterinary hospital from October 1, 2008, through November 30, 2017. PROCEDURES: Medical records were reviewed to obtain information on dog signalment, surgical procedure, and radiographically measured PLL at preoperative, postoperative, and follow-up evaluations. RESULTS: Dogs undergoing TPLO had a shorter PLL at the postoperative and follow-up evaluations, compared with the PLL at the preoperative evaluation. Mean ± SD overall unadjusted PLL decreased significantly by 2.3 ± 3.4% between the preoperative and postoperative evaluation and by 2.8 ± 3.9% between the preoperative and follow-up evaluation. The PLL did not differ significantly between the postoperative and follow-up evaluation; mean PLL decreased by 0.4 ± 3.8% between the postoperative and follow-up evaluation. CONCLUSIONS AND CLINICAL RELEVANCE: The PLL was shorter after TPLO in dogs, which was similar to changes observed for humans after high tibial osteotomy procedures. Further evaluation of clinical assessments, joint mobility, ultrasonographic assessments, and kinematic results are needed to determine the relevance of the PLL and whether a decrease in ligament length results in decreased mobility and persistent lameness in dogs, as has been reported for humans.

Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase.

Despite advancements in therapies for cardiovascular disease and heart failure (HF), the incidence and prevalence of HF are increasing. Previous work has suggested that inhibiting adipose triglyceride lipase (ATGL) in adipose tissue during HF development may assist in the treatment of HF. The ability to specifically target the adipocyte as a potential treatment for HF is a novel approach that could significantly influence the management of HF in the future. Our objectives were to assess the cardiac structural and functional effects of pharmacological inhibition of ATGL in mice with HF, to assess whether ATGL inhibition works in an adipocyte-autonomous manner, and to determine the role that adiposity and glucose homeostasis play in this HF treatment approach. Using a known ATGL inhibitor, atglistatin, as well as mice with germline deletion of adipocyte-specific ATGL, we tested the effectiveness of ATGL inhibition in mice with pressure overload-induced HF. Here, we show that atglistatin can prevent the functional decline in HF and provide evidence that specifically targeting ATGL in the adipocyte is sufficient to prevent worsening of HF. We further demonstrate that the benefit resulting from atglistatin in HF is not dependent on previously suggested improvements in glucose homeostasis, nor are the benefits derived from increased adiposity. Overall, the results of this study suggest that adipocyte-specific pharmacological inhibition of ATGL may represent a novel therapeutic option for HF. NEW & NOTEWORTHY This work shows for the first time that the adipose triglyceride lipase (ATGL)-specific inhibitor atglistatin can prevent worsening heart failure. Furthermore, using mice with adipocyte-specific ATGL ablation, this study demonstrates that ATGL inhibition works in an adipocyte-autonomous manner to ameliorate a functional decline in heart failure. Overall, this work demonstrates that specifically targeting the adipocyte to inhibit ATGL is a potential treatment for heart failure.

Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice.

Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.

Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure.

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg-1·day-1) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients.NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms.

Cardiomyocyte-specific ablation of CD36 accelerates the progression from compensated cardiac hypertrophy to heart failure.

Previous studies have shown that loss of CD36 protects the heart from dysfunction induced by pressure overload in the presence of diet-induced insulin resistance and/or obesity. The beneficial effects of CD36 ablation in this context are mediated by preventing excessive cardiac fatty acid (FA) entry and reducing lipotoxic injury. However, whether or not the loss of CD36 can prevent pressure overload-induced cardiac dysfunction in the absence of chronic exposure to high circulating FAs is presently unknown. To address this, we utilized a tamoxifen-inducible cardiomyocyte-specific CD36 knockout (icCD36KO) mouse and genetically deleted CD36 in adulthood. Control mice (CD36 floxed/floxed mice) and icCD36KO mice were treated with tamoxifen and subsequently subjected to transverse aortic constriction (TAC) surgery to generate pressure overload-induced cardiac hypertrophy. Consistent with CD36 mediating a significant proportion of FA entry into the cardiomyocyte and subsequent FA utilization for ATP production, hearts from icCD36KO mice were metabolically inefficient and displayed signs of energetic stress, including activation of the energetic stress kinase, AMPK. In addition, impaired energetics in icCD36KO mice contributed to a rapid progression from compensated hypertrophy to heart failure. However, icCD36KO mice fed a medium-chain FA diet, whereby medium-chain FAs can enter into the cardiomyocyte independent from CD36, were protected from TAC-induced heart failure. Together these data suggest that limiting FA uptake and partial inhibition of FA oxidation in the heart via CD36 ablation may be detrimental for the compensated hypertrophic heart in the absence of sufficiently elevated circulating FAs to provide an adequate energy source.NEW & NOTEWORTHY Limiting CD36-mediated fatty acid uptake in the setting of obesity and/or insulin resistance protects the heart from cardiac hypertrophy and dysfunction. However, cardiomyocyte-specific CD36 ablation in the absence of elevated circulating fatty acid levels accelerates the progression of pressure overload-induced cardiac hypertrophy to systolic heart failure.

Improved Glucose Homeostasis in Obese Mice Treated With Resveratrol Is Associated With Alterations in the Gut Microbiome.

Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol.

Monitoring and malignancy concerns in patients with congenital bladder anomalies.

PURPOSE OF REVIEW: There are concerns that patients with congenital bladder anomalies (CBA) may be at higher risk for developing bladder malignancy later in life. To date there is no consensus on how to monitor these patients to prevent this devastating malignancy. We will review the current understanding of bladder malignancy in patients with CBA and the status of surveillance tests. RECENT FINDINGS: Initial reports observed that augmentation cystoplasty in CBA may be an independent risk factor for bladder malignancy. Since that time, studies have identified that the augmented bladder may not be the culprit, but the congenital bladder itself may be at risk. Further, reports determined cystoscopy and cytology are not cost-effective at detecting these malignancies. Bladder cancer in these patients at presentation is typically aggressive and presents at a younger age, high stage with high mortality. SUMMARY: Surveillance cystoscopy and cytology of the adult congenital bladder should be discontinued as the evidence shows they are not effective, given the low incidence, high cost, and inability to alter the course of disease. Symptomatic patients should prompt a detailed evaluation for bladder cancer using standard testing.

The role of CD36 in the regulation of myocardial lipid metabolism.

Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50-70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.

Is AMPK the savior of the failing heart?

Heart failure (HF) is one of the leading causes of death, affecting more than 20 million people worldwide. A vast array of pathophysiological and molecular events contributes to the development and eventual worsening of HF. Of these, defects in myocardial metabolic processes that normally result in proper ATP production necessary to maintain contractile function appear to be a major contributor to HF pathogenesis. A key player involved in regulating myocardial metabolism is AMP-activated protein kinase (AMPK), a major regulatory kinase controlling numerous metabolic pathways. Here, we review the metabolic changes that occur in HF, what role alterations in energy metabolism has in its progression, and the involvement of AMPK in this context.

Resveratrol treatment of mice with pressure-overload-induced heart failure improves diastolic function and cardiac energy metabolism.

BACKGROUND: Although resveratrol has multiple beneficial cardiovascular effects, whether resveratrol can be used for the treatment and management of heart failure (HF) remains unclear. In the current study, we determined whether resveratrol treatment of mice with established HF could lessen the detrimental phenotype associated with pressure-overload-induced HF and identified physiological and molecular mechanisms contributing to this. METHODS AND RESULTS: C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks post surgery, a cohort of mice with established HF (% ejection fraction <45) was administered resveratrol (≈320 mg/kg per day). Despite a lack of improvement in ejection fraction, resveratrol treatment significantly increased median survival of mice with HF, lessened cardiac fibrosis, reduced gene expression of several disease markers for hypertrophy and extracellular matrix remodeling that were upregulated in HF, promoted beneficial remodeling, and improved diastolic function. Resveratrol treatment of mice with established HF also restored the levels of mitochondrial oxidative phosphorylation complexes, restored cardiac AMP-activated protein kinase activation, and improved myocardial insulin sensitivity to promote glucose metabolism and significantly improved myocardial energetic status. Finally, noncardiac symptoms of HF, such as peripheral insulin sensitivity, vascular function, and physical activity, were improved with resveratrol treatment. CONCLUSIONS: Resveratrol treatment of mice with established HF lessens the severity of the HF phenotype by lessening cardiac fibrosis, improving molecular and structural remodeling of the heart, and enhancing diastolic function, vascular function, and energy metabolism.

Management of the devastated posterior urethra and bladder neck: refractory incontinence and stenosis.

Stricture of the proximal urethra following treatment for prostate cancer occurs in an estimated 1-8% of patients. Following prostatectomy, urethral reconstruction is feasible in many patients. However, in those patients with prior radiation therapy (RT), failed reconstruction, refractory incontinence or multiple comorbidities, reconstruction may not be feasible. The purpose of this article is to review the evaluation and management options for patients who are not candidates for reconstruction of the posterior urethra and require urinary diversion. Patient evaluation should result in the decision whether reconstruction is feasible. In our experience, risk factors for failed reconstruction include prior radiation and multiple failed endoscopic treatments. Pre-operative cystoscopy is an essential part of the evaluations to identify tissue necrosis, dystrophic calcification, or tumor in the urethra, prostate and/or bladder. If urethral reconstruction is not feasible it is imperative to discuss options for urine diversion with the patient. Treatment options include simple catheter diversion, urethral ligation, and both bladder preserving and non-preserving diversion. Surgical management should address both the bladder and the bladder outlet. This can be accomplished from a perineal, abdominal or abdomino-perineal approach. The devastated bladder outlet is a challenging problem to treat. Typically, patients undergo multiple procedures in an attempt to restore urethral continuity and continence. For the small subset who fails reconstruction, urinary diversion provides a definitive, "end-stage" treatment resulting in improved quality of life.

Forming a supplement intervention using a multi-theoretical behavior model.

OBJECTIVES: To identify behavior theory-based strategies to improve compliance with daily multiple micronutrient supplementation (MMS) among rural Ghanaian women. METHODS: Components of a multi-theoretical framework were investigated in focus groups of reproductive-aged women in 6 communities. RESULTS: Participants were generally unaware of MMS' purpose. Perceived benefits included better health and stimulated appetite, which some believe escalates food purchases and financial constraints. Cost, forgetfulness, and unsustainability were also perceived barriers. Facilitators for compliance incorporated initial visual reminders and daily announcements with reinforcement using the 'keeper' system. CONCLUSIONS: Application of a tailored health behavioral model can effectively guide the design, implementation and evaluation of community-based MMS interventions.

Development and validation of the Indian Adolescent Health Questionnaire.

The period of adolescence is a critical time of development. There is an urgent need to better assess adolescent health worldwide, particularly in India, a country with the world's largest adolescent population. Validated screening tools are needed to evaluate health-related risks and behaviors in this growing demographic. We developed, validated and administered a school-based health assessment, the Indian Adolescent Health Questionnaire, which can be used as a comprehensive health-screening tool among Indian adolescents in secondary school.

Evaluation and treatment of adult concealed penis.

Concealed penis is a rare congenital disorder most commonly seen in children and the condition and surgical management have been well described. In contrast, there is a paucity of information with regards to adult concealed penis. Adult concealed penis may be due to trapping from skin contraction related to lichen sclerosis, cicatricial scars following surgical procedures, or prepubic adipose tissue causing poor phallic exposure. One of the greatest risk factors for concealed penis is obesity, and as this becomes a national pandemic, the incidence of adult concealed penis may increase. Therefore, a greater number of urologists may be faced with treating this difficult condition. This article reviews the etiology of adult concealed penis and describes the patient evaluation and various surgical approaches.

Congenital penile curvature: update and management.

Congenital penile curvature results from disproportionate development of the tunica albuginea of the corporal bodies and is not associated with urethral malformation. Patients usually present after reaching puberty as the curvature becomes more apparent with erections, and severe curvature can make intercourse difficult or impossible, at which point surgical repair is recommended. Excellent outcomes can be expected with surgical intervention. The three most commonly used repair techniques are the original Nesbit procedure, modified Nesbit procedure, and plication. Nesbit and modified Nesbit techniques require that an incision is made in the tunica albuginea while plication techniques utilize plicating sutures without an incision. While Nesbit and modified Nesbit techniques are more complex operations, these generally result in less recurrences and more satisfactory outcomes as opposed to the quicker and simpler plication technique.