Understanding barriers to men's support for family planning in rural Ethiopia-findings from the USAID Transform: Primary Health Care Project Gender Analysis.

BACKGROUND: Evidence suggests that supportive male engagement in health care services, including family planning, remains low in many countries, despite known benefits for female partners. In 2017-2018, the United States Agency for International Development Transform: Primary Health Care Project conducted a participatory gender analysis, collecting relevant data to better understand Ethiopian men's lack of support for the uptake of family planning services. METHODS: Qualitative data were collected through 96 unique participatory group discussions with community members via a semistructured discussion guide and participatory activity; data were disaggregated by sex, age, and marital status. In-depth interviews (91) conducted with service providers, health system managers, and health extension workers used semistructured guides. Discussants and interviewees were selected purposefully, drawn from 16 rural woredas in four project regions: Amhara; Oromia; Tigray; and Southern Nations, Nationalities, and Peoples' Region. Data collectors took notes and transcribed audio recordings. The research team deductively and inductively coded transcripts to develop preliminary findings later validated by key technical project staff and stakeholders. RESULTS: Findings reinforce existing knowledge on the dominant role of men in health care-related decision making in rural Ethiopia, although such decision making is not always unilateral in practice. Barriers at the societal level impede men's support for family planning; these include norms, values, and beliefs around childbearing; religious beliefs rooted in scriptural narratives; and perceived adverse health impacts of family planning. Lack of efforts to engage men in health care facilities, as well as the perception that health care facilities do not meet men's needs, highlight systems-level barriers to men's use of family planning services. CONCLUSIONS: Findings indicate several opportunities for stakeholders to increase men's support for family planning in rural Ethiopia, including systems-wide approaches to shape decision making, social and behavior change communication efforts, and additional research and assessment of men's experiences in accessing health care services.

Evidence suggests that in instances where men participate when their partners access health care services, their partners experience positive health benefits. Regardless, men tend not to participate. During 2017­2018, the United States Agency for International Development Transform: Primary Health Care Project conducted research to identify gender-related issues that hinder the delivery of primary health care services in Ethiopia. The research team conducted 96 group discussions with male and female community members, as well as 91 in-depth interviews with health care service providers, health system managers, and health extension workers. Participants were specifically selected from 16 rural districts, or woredas, in four regions where the project is active. The researchers then categorized information in the resulting transcripts by common themes, and the data analysis team met to draw out the main findings. Later, a meeting was held with key project staff and stakeholders in Addis Ababa to verify the findings. Findings reinforce existing knowledge on the dominant role of men in health care­related decision making for households in rural Ethiopia, although women often play an important role as well. The research also identified widespread male opposition to family planning due to norms, desires, and societal perceptions around childbearing; religious beliefs; and concerns about the perceived health risks of family planning methods. Further, findings showed that the promotion of family planning methods and services do not explicitly target men, and men believe that current services do not respond to their needs. Respondents suggested opportunities for stakeholders to mitigate these barriers.

The Spiritual Assessment.

The spiritual assessment offers the opportunity to enhance the patient-physician relationship and incorporate patient views that may have a significant impact on clinical decision-making. Multiple studies have demonstrated that patients' expectations of spiritual discussions in the health care setting are not being met. Perceived barriers reported by physicians include lack of time, training, and experience. There is a variety of physician approaches to assess and incorporate spirituality in the health care setting. A spiritual assessment is recommended when a patient is admitted to the hospital, has a significant clinical decline while in the hospital, is receiving psychosocial services for the treatment of substance use disorder, or when addressing palliative care. Tools for spiritual assessment include the Open Invite mnemonic, which initiates the topic and relies on a conversational approach, and the HOPE questions, which offer a structured approach to determine the relevance of spirituality to the patient's overall health and assist with the development of an individualized care plan. Although physicians should respect the right of patients who do not want to discuss this topic, multiple studies demonstrate significant relationships between spiritual interventions and improved mental and physical health outcomes.

Development of a Real-Time Pectic Oligosaccharide-Detecting Biosensor Using the Rapid and Flexible Computational Identification of Non-Disruptive Conjugation Sites (CINC) Biosensor Design Platform.

Fluorescently labeled, solute-binding proteins that change their fluorescent output in response to ligand binding are frequently used as biosensors for a wide range of applications. We have previously developed a "Computational Identification of Non-disruptive Conjugation sites" (CINC) approach, an in silico pipeline utilizing molecular dynamics simulations for the rapid design and construction of novel protein-fluorophore conjugate-type biosensors. Here, we report an improved in silico scoring algorithm for use in CINC and its use in the construction of an oligogalacturonide-detecting biosensor set. Using both 4,5-unsaturated and saturated oligogalacturonides, we demonstrate that signal transmission from the ligand-binding pocket of the starting protein scaffold to the CINC-selected reporter positions is effective for multiple different ligands. The utility of an oligogalacturonide-detecting biosensor is shown in Carbohydrate Active Enzyme (CAZyme) activity assays, where the biosensor is used to follow product release upon polygalacturonic acid (PGA) depolymerization in real time. The oligogalacturonide-detecting biosensor set represents a novel enabling tool integral to our rapidly expanding platform for biosensor-based carbohydrate detection, and moving forward, the CINC pipeline will continue to enable the rational design of biomolecular tools to detect additional chemically distinct oligosaccharides and other solutes.

Comparative nutrient analysis of four species of cockroaches used as food for insectivores by life stage, species, and sex.

A variety of insects are fed to insectivorous animals; however, nutritional analyses are often limited to adult life stages. Four species of nymph and adult female and male cockroaches (Blaberus giganteus, Blaptica dubia, Blatta lateralis, and Gromphadorhina portentosa) were analyzed for moisture, crude protein (CP), acid detergent fiber (ADF), fat, ash, and mineral content. The small sample size of this study precluded statistical analyses, however comparatively, CP in adult B. lateralis and B. dubia was greater than the CP in nymphs of the same species. Adult and nymph B. dubia had the greatest CP (96.6% and 65.3%, respectively) compared to the other three species. Inversely, fat content in adult B. lateralis and B. dubia was lower than that of nymphs of the same species. All adults contained similar levels of ADF, yet adult B. giganteus had greater ADF than nymphs; conversely, B. lateralis and B. dubia adults had less ADF than nymphs. There were differences noted in mineral parameters among the four species and life stages. Adult B. giganteus had less Ca than G. portentosa, and the lowest Ca content of the four species of nymphs and adults analyzed. This study underscores the differences in nutrient content with respect to life stage and species in previously understudied cockroaches to improve nutrient intake in captive insectivores.

Cane toad (Rhinella marina) vitamin A, vitamin E, and carotenoid kinetics.

Many amphibian species are threatened with extinction. Understanding their vitamin A (retinol), E (alpha-tocopherol), and carotenoid requirements is vital, as normal levels of these nutrients have a known connection to breeding success with abnormal levels leading to disease. This research examined vitamins A, E, and carotenoids (apocarotenoid, beta-carotene; beta-cryptoxanthin, lutein, zeaxanthin, and esters) concentration kinetics in the liver and plasma of 65 (57.8) cane toads (Rhinella marina) over 4 months supplemented with commercially available invertebrates in human care. Cane toads were opportunistically collected as part of a population control program for use as an amphibian model species. Toads were randomly assigned to one of two diets: treatment 1 was brown house crickets (Acheta domesticus) consuming Mazuri® Hi Calcium Gut Loading Diet without vitamin A or E supplement, plus fresh raw vegetables (carrot/sweet potato); Treatment 2 was the same diet except no vegetables. Ten toads were euthanized on Day 0 to analyze baseline free-ranging liver and plasma metabolites. Six toads consuming each treatment were euthanized on Days 22, 50, and 81, and n = 7 on Day 119 for analysis. Regardless of dietary treatment, most liver and blood metabolites were substantially higher at time 0 than all time points thereafter (p < .05); Ex: liver vitamin A at time 0 was 87.7 ± 16.12 µg/g while Day 119 for treatments 1 and 2 were 11.6 ± 1.19 and 8.2 ± 0.74, respectively. Few statistically significant differences between diets at the same time point were noted (p < .05). The results from this study indicate that additional or alternative diet supplementation may be needed for cane toads (and potentially other amphibians) to mimic their free-ranging diets.

Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1).

Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer (NSCLC) most likely to respond to single-agent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC. PD-L1 expression on IC was more prevalent and likely reflected IFN-γ-induced adaptive regulation accompanied by increased tumor-infiltrating lymphocytes and effector T cells. High PD-L1 expression on TC, however, reflected an epigenetic dysregulation of the PD-L1 gene and was associated with a distinct histology described by poor immune infiltration, sclerotic/desmoplastic stroma, and mesenchymal molecular features. Importantly, durable clinical responses to atezolizumab (anti-PD-L1) were observed in patients with tumors expressing high PD-L1 levels on either TC alone [40% objective response rate (ORR)] or IC alone (22% ORR). Thus, PD-L1 expression on TC or IC can independently attenuate anticancer immunity and emphasizes the functional importance of IC in regulating the antitumor T cell response.

Community-Acquired Pneumonia in Children: Rapid Evidence Review.

In the United States, pneumonia is the most common cause of hospitalization in children. Even in hospitalized children, community-acquired pneumonia is most likely of viral etiology, with respiratory syncytial virus being the most common pathogen, especially in children younger than two years. Typical presenting signs and symptoms include tachypnea, cough, fever, and anorexia. Findings most strongly associated with an infiltrate on chest radiography in children with clinically suspected pneumonia are grunting, history of fever, retractions, crackles, tachypnea, and the overall clinical impression. Chest radiography should be ordered if the diagnosis is uncertain, if patients have hypoxemia or significant respiratory distress, or if patients fail to show clinical improvement within 48 to 72 hours after initiation of antibiotic therapy. Outpatient management of community-acquired pneumonia is appropriate in patients without respiratory distress who can tolerate oral antibiotics. Amoxicillin is the first-line antibiotic with coverage for Streptococcus pneumoniae for school-aged children, and treatment should not exceed seven days. Patients requiring hospitalization and empiric parenteral therapy should be transitioned to oral antibiotics once they are clinically improving and able to tolerate oral intake. Childhood and maternal immunizations against S. pneumoniae, Haemophilus influenzae type b, Bordetella pertussis, and influenza virus are the key to prevention.

URINARY CORTICOSTERONE CONCENTRATIONS IN FREE-RANGING AND MANAGED CANE TOADS (RHINELLA MARINA).

Approximately 40% of amphibian species are threatened with extinction. The welfare of amphibians maintained under managed care as assurance populations is of vital importance to guard against extinction and provide a viable source population for future reintroduction. To manage amphibian species properly ex situ, it is important to understand how stress levels change over time when animals are removed from the wild and placed into managed environments. Corticosterone was analyzed in urine samples from free-ranging cane toads (Rhinella marina, n = 55) in Miami, FL, and under managed care for 22 (n = 48), 50 (n = 11), 81 (n = 25), or 119 (n = 10) days. Concentrations of corticosterone in free-ranging toad urine averaged 1.74 ± 0.195 ng/ml urine specific gravity (sp. gr.), which was greater (P < 0.05) than other time points (day 22: 0.77 ± 0.114 L; day 81: 0.85 ± 0.191 ng/ml sp. gr.; day 119: 0.58 ± 0.093 ng/ml sp. gr.), except day 50 (0.91 ± 0.274 ng/ml sp. gr.), which was not different from free-ranging or managed care values. Thus, corticosterone was lower in cane toads under managed care compared with those sampled in the wild, suggesting that managed care is not a stressor for this species.

Managing Hypertension Using Combination Therapy.

More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control. Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker. Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB (or an angiotensin receptor-neprilysin inhibitor), followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status. Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker. Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB.

Identification of novel azaindazole CCR1 antagonist clinical candidates.

Exploring various cyclization strategies, using a submicromolar pyrazole HTS screening hit 6 as a starting point, a novel indazole based CCR1 antagonist core was discovered. This report presents the design and SAR of CCR1 indazole and azaindazole antagonists leading to the identification of three development compounds, including 19e that was advanced to early clinical trials.

Febrile Seizures: Risks, Evaluation, and Prognosis.

A febrile seizure is a seizure occurring in a child six months to five years of age that is accompanied by a fever (100.4°F or greater) without central nervous system infection. Febrile seizures are classified as simple or complex. A complex seizure lasts 15 minutes or more, is associated with focal neurologic findings, or recurs within 24 hours. The cause of febrile seizures is likely multifactorial. Viral illnesses, certain vaccinations, and genetic predisposition are common risk factors that may affect a vulnerable, developing nervous system under the stress of a fever. Children who have a simple febrile seizure and are well-appearing do not require routine diagnostic testing (laboratory tests, neuroimaging, or electroencephalography), except as indicated to discern the cause of the fever. For children with complex seizures, the neurologic examination should guide further evaluation. For seizures lasting more than five minutes, a benzodiazepine should be administered. Febrile seizures are not associated with increased long-term mortality or negative effects on future academic progress, intellect, or behavior. Children with febrile seizures are more likely to have recurrent febrile seizures. However, given the benign nature of febrile seizures, the routine use of antiepileptics is not indicated because of adverse effects of these medications. The use of antipyretics does not decrease the risk of febrile seizures, although rectal acetaminophen reduced the risk of short-term recurrence following a febrile seizure. Parents should be educated on the excellent prognosis of children with febrile seizures and provided with practical guidance on home management of seizures.

Acute Kidney Injury: Diagnosis and Management.

Acute kidney injury is a clinical syndrome characterized by a rapid decline in glomerular filtration rate and resultant accumulation of metabolic waste products. Acute kidney injury is associated with an increased risk of mortality, cardiovascular events, and progression to chronic kidney disease. Severity of acute kidney injury is classified according to urine output and elevations in creatinine level. Etiologies of acute kidney injury are categorized as prerenal, intrinsic renal, and postrenal. Accurate diagnosis of the underlying cause is key to successful management and includes a focused history and physical examination, serum and urine electrolyte measurements, and renal ultrasonography when risk factors for a postrenal cause are present (e.g., older male with prostatic hypertrophy). General management principles for acute kidney injury include determination of volume status, fluid resuscitation with isotonic crystalloid, treatment of volume overload with diuretics, discontinuation of nephrotoxic medications, and adjustment of prescribed drugs according to renal function. Additional supportive care measures may include optimizing nutritional status and glycemic control. Pharmacist-led quality-improvement programs reduce nephrotoxic exposures and rates of acute kidney injury in the hospital setting. Acute kidney injury care bundles are associated with improved in-hospital mortality rates and reduced risk of progression. Nephrology consultation should be considered when there is inadequate response to supportive treatment and for acute kidney injury without a clear cause, stage 3 or higher acute kidney injury, preexisting stage 4 or higher chronic kidney disease, renal replacement therapy, and other situations requiring subspecialist expertise.

Emergency Department Thoracotomy: A Cost-Effective Model for Simulation Training.

BACKGROUND: Simulation provides a safe learning environment where high-stakes, low-frequency procedures can be practiced without the fear of being unsuccessful or causing harm. Emergency department thoracotomy (EDT) is one such procedure. Realistic thoracotomy models are expensive and not readily available. OBJECTIVE: Our objective is to describe a cost-effective, realistic, reproducible, and reusable thoracotomy model for simulation training. METHODS: We modified a commercially available clothes mannequin torso to expose the chest and abdominal cavity. A plastic skeleton composed of a spinal cord and ribs was placed inside the torso. Tubing was used to simulate the aorta and esophagus; both tubes were secured to the distal spine with zip ties. Commercially available lungs and heart were placed inside the chest cavity. A small rubber ball simulated the left lung to be able to maneuver the lung. The heart was covered with plastic wrap to simulate the pericardium. Thick tape was used to simulate the pleural cavity. Yoga mats were used to simulate the intercostal muscles, subcutaneous tissue, and skin. RESULTS: This model was tested with Emergency Medicine (EM) residents during a simulation session. A voluntary survey was available for residents to provide feedback. Survey results confirmed that the model provided valuable education, with overall positive feedback. CONCLUSION: This EDT model provides a valuable teaching opportunity to EM residents who otherwise might not have the opportunity to perform this procedure. Residents agreed that the model improved their confidence and is an effective method in providing the opportunity to practice this low-frequency, high-stakes procedure.

Identification and Characterization of a Selective Human Carbonyl Reductase 1 Substrate.

During drug discovery efforts targeting inhibition of cytochrome P450 11B2 (CYP11B2)-mediated production of aldosterone as a therapeutic approach for the treatment of chronic kidney disease and hypertension, (S)-6-(5-fluoro-4-(1-hydroxyethyl)pyridin-3-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (1) was identified as a potent and selective inhibitor of CYP11B2. Preclinical studies characterized 1 as low clearance in both in vitro test systems and in vivo in preclinical species. Despite low metabolic conversion, an active ketone metabolite (2) was identified from in vitro metabolite-identification studies. Due to the inhibitory activity of 2 against CYP11B2 as well as the potential for it to undergo reductive metabolism back to 1, the formation and elimination of 2 were characterized and are the focus of this manuscript. A series of in vitro investigations determined that 1 was slowly oxidized to 2 by cytochrome P450s 2D6, 3A4, and 3A5, followed by stereoselective reduction back to 1 and not its enantiomer (3). Importantly, reduction of 2 was mediated by an NADPH-dependent cytosolic enzyme. Studies with human cytosolic fractions from multiple tissues, selective inhibitors, and recombinantly expressed enzymes indicated that carbonyl reductase 1 (CBR1) is responsible for this transformation in humans. Carbonyl reduction is emerging as an important pathway for endogenous and xenobiotic metabolism. With a lack of selective substrates and inhibitors to enable characterization of the involvement of CBR1, 2 could be a useful probe to assess CBR1 activity in vitro in both subcellular fractions and in cell-based systems.

Croup: Diagnosis and Management.

Croup is a common respiratory illness affecting 3% of children six months to three years of age. It accounts for 7% of hospitalizations annually for fever and/or acute respiratory illness in children younger than five years. Croup is a manifestation of upper airway obstruction resulting from swelling of the larynx, trachea, and bronchi, leading to inspiratory stridor and a barking cough. Many patients experience low-grade fevers, but fever is not necessary for diagnosis. Less commonly, stridor can be associated with acute epiglottitis, bacterial tracheitis, and foreign body airway obstruction. Laboratory studies are seldom needed for diagnosis of croup. Viral cultures and rapid antigen testing have minimal impact on management and are not routinely recommended. Radiography and laryngoscopy should be reserved for patients in whom alternative diagnoses are suspected. Randomized controlled trials have demonstrated that a single dose of oral, intramuscular, or intravenous dexamethasone improves symptoms and reduces return visits and length of hospitalization in children with croup of any severity. In patients with moderate to severe croup, the addition of nebulized epinephrine improves symptoms and reduces length of hospitalization.

Streamlined purification of fluorescently labeled Escherichia coli phosphate-binding protein (PhoS) suitable for rapid-kinetics applications.

Fluorescently labeled phosphate-binding proteins can be used as biomolecular tools to measure the release of inorganic phosphate (Pi) from enzymes in real time, enabling the detailed kinetic analysis of dephosphorylating enzymes using rapid-kinetics approaches. Previously reported methods to purify fluorescently labeled phosphate-binding proteins (PhoS) from Escherichia coli are laborious, and a simplified approach is needed. Here, we report the characterization of a cytosol-localized variant (A197C) of PhoS that allows a streamlined purification for subsequent covalent conjugation with a fluorescent dye. We show that export of PhoS into the periplasmic space is not required for the fluorescence-based detection of Pi binding. Furthermore, we report the addition of a C-terminal His-tag, simplifying the purification of PhoS from the cytosol via Ni2+-affinity chromatography, yielding a fully functional fusion protein (HC PhoS A197C). We demonstrate the utility of fluorescently labeled HC PhoS A197C for rapid-kinetics applications by measuring, using stopped-flow, the Pi release kinetics from LepA/EF4 following 70S ribosome-stimulated GTP hydrolysis. Altogether, the approach developed here allows for the high-yield and simplified in-house production of a Pi detection system suitable for rapid-kinetics approaches with comparable sensitivity to the commercially available Phosphate Sensor.

Respiratory Syncytial Virus Bronchiolitis in Children.

Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause of this infection. RSV is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. Patients with RSV bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower respiratory tract symptoms such as increasing cough, wheezing, and increased respiratory effort. In 2014, the American Academy of Pediatrics updated its clinical practice guideline for diagnosis and management of RSV bronchiolitis to minimize unnecessary diagnostic testing and interventions. Bronchiolitis remains a clinical diagnosis, and diagnostic testing is not routinely recommended. Treatment of RSV infection is mainly supportive, and modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and antibiotics are generally not useful. Evidence supports using supplemental oxygen to maintain adequate oxygen saturation; however, continuous pulse oximetry is no longer required. The other mainstay of therapy is intravenous or nasogastric administration of fluids for infants who cannot maintain their hydration status with oral fluid intake. Educating parents on reducing the risk of infection is one of the most important things a physician can do to help prevent RSV infection, especially early in life. Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.