Effectiveness of clinical training on improving essential newborn care practices in Bossaso, Somalia: a pre and postintervention study.

BACKGROUND: Increasingly, neonatal mortality is concentrated in settings of conflict and political instability. To promote evidence-based practices, an interagency collaboration developed the Newborn Health in Humanitarian Settings: Field Guide. The essential newborn care component of the Field Guide was operationalized with the use of an intervention package encompassing the training of health workers, newborn kit provisions and the installation of a newborn register. METHODS: We conducted a quasi-experimental prepost study to test the effectiveness of the intervention package on the composite outcome of essential newborn care from August 2016 to December 2018 in Bossaso, Somalia. Data from the observation of essential newborn care practices, evaluation of providers' knowledge and skills, postnatal interviews, and qualitative information were analyzed. Differences in two-proportion z-tests were used to estimate change in essential newborn care practices. A generalized estimating equation was applied to account for clustering of practice at the health facility level. RESULTS: Among the 690 pregnant women in labor who sought care at the health facilities, 89.9% (n = 620) were eligible for inclusion, 84.7% (n = 525) were enrolled, and newborn outcomes were ascertained in 79.8% (n = 419). Providers' knowledge improved from pre to posttraining, with a mean difference in score of + 11.9% (95% CI: 7.2, 16.6, p-value < 0.001) and from posttraining to 18-months after training with a mean difference of + 10.9% (95% CI: 4.7, 17.0, p-value < 0.001). The proportion of newborns who received two or more essential newborn care practices (skin-to-skin contact, early breastfeeding, and dry cord care) improved from 19.9% (95% CI: 4.9, 39.7) to 94.7% (95% CI: 87.7, 100.0). In the adjusted model that accounted for clustering at health facilities, the odds of receiving two or more essential newborn practices was 64.5 (95% CI: 15.8, 262.6, p-value < 0.001) postintervention compared to preintervention. Predischarge education offered to mothers on breastfeeding 16.5% (95% CI: 11.8, 21.1) vs 44.2% (95% CI: 38.2, 50.3) and newborn illness danger signs 9.1% (95% CI: 5.4, 12.7) vs 5.0% (95% CI: 2.4, 7.7) remained suboptimal. CONCLUSIONS: The intervention package was feasible and effective in improving essential newborn care. Knowledge and skills gained after training were mostly retained at the 18-month follow-up.

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling.

The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular-vascular uncoupling and adverse ventricular-ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force-specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.

KLF2-mediated disruption of PPAR-γ signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow.

Lymphatic abnormalities associated with congenital heart disease are well described, yet the underlying mechanisms remain poorly understood. Using a clinically relevant ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated that lymphatic endothelial cells (LECs) exposed in vivo to chronically increased pulmonary lymph flow accumulate ROS and have decreased bioavailable nitric oxide (NO). Peroxisome proliferator-activated receptor-γ (PPAR-γ), which abrogates production of cellular ROS by NADPH oxidase, is inhibited by Krüppel-like factor 2 (KLF2), a flow-induced transcription factor. We hypothesized that chronically increased pulmonary lymph flow induces a KLF2-mediated decrease in PPAR-γ and an accumulation of cellular ROS, contributing to decreased bioavailable NO in LECs. To better understand the mechanisms that transduce the abnormal mechanical forces associated with chronically increased pulmonary lymph flow, LECs were isolated from the efferent vessel of the caudal mediastinal lymph node of control ( n = 5) and shunt ( n = 5) lambs. KLF2 mRNA and protein were significantly increased in shunt compared with control LECs, and PPAR-γ mRNA and protein were significantly decreased. In control LECs exposed to shear forces in vitro, we found similar alterations to KLF2 and PPAR-γ expression. In shunt LECs, NADPH oxidase subunit expression was increased, and bioavailable NO was significantly lower. Transfection of shunt LECs with KLF2 siRNA normalized PPAR-γ, ROS, and bioavailable NO. Conversely, pharmacological inhibition of PPAR-γ in control LECs increased ROS equivalent to levels in shunt LECs at baseline. Taken together, these data suggest that one mechanism by which NO-mediated lymphatic function is disrupted after chronic exposure to increased pulmonary lymph flow is through altered KLF2-dependent PPAR-γ signaling, resulting in increased NADPH oxidase activity, accumulation of ROS, and decreased bioavailable NO. NEW & NOTEWORTHY Lymphatic endothelial cells, when exposed in vivo to chronically elevated pulmonary lymph flow in a model of congenital heart disease with increased pulmonary blood flow, demonstrate Krüppel-like factor 2-dependent disrupted peroxisome proliferator-activated receptor-γ signaling that results in the accumulation of reactive oxygen species and decreased bioavailable nitric oxide.

Cytotoxic Swelling of Sick Excitable Cells - Impaired Ion Homeostasis and Membrane Tension Homeostasis in Muscle and Neuron.

When they become simultaneously leaky to both Na+ and Cl-, excitable cells are vulnerable to potentially lethal cytotoxic swelling. Swelling ensues in spite of an isosmotic milieu because the entering ions add osmolytes to the cytoplasm's high concentration of impermeant anionic osmolytes. An influx of osmotically-obliged water is unavoidable. A cell that cannot stanch at least one the leaks will succumb to death by Donnan effect. "Sick excitable cells" are those injured through ischemia, trauma, inflammation, hyperactivity, genetically-impaired membrane skeletons and other insults, all of which foster bleb-damage to regions of the plasma membrane. Nav channels resident in damaged membrane exhibit left-shifted kinetics; the corresponding Nav window conductance constitutes a Na+-leak. In cortical neurons, sustained depolarization to ∼-20mV elicits a sustained lethal gCl. Underlying Vrest in skeletal muscle is a constitutively active gCl; not surprisingly therefore, dystrophic muscle fibers, which are prone to bleb damage and which exhibit Nav-leak and Na+-overload, are prone to cytotoxic swelling. To restore viability in cytotoxically swelling neurons and muscle, the imperative of fully functional ion homeostasis is well-recognized. However, as emphasized here, in a healthy excitable cell, fully functional membrane tension homeostasis is also imperative. ATPase-pumps keep plasma membrane batteries charged, and ATPase-motor proteins maintain membrane tone. In sick excitable cells, neither condition prevails.

Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick Excitable Cells.

Two features common to diverse sick excitable cells are "leaky" Nav channels and bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel kinetics based "leakiness." Recombinant (node of Ranvier type) Nav1.6 channels voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage intensity dependent kinetic change. Specifically, they experience a coupled hyperpolarizing (left) shift of the activation and inactivation processes. The biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left Shift (Nav-CLS) theory. Node of Ranvier excitability can be modeled with Nav-CLS imposed at varying LS intensities and with varying fractions of total nodal membrane affected. Mild damage from which sick excitable cells might recover is of most interest pathologically. Accordingly, Na+/K+ ATPase (pump) activity was included in the modeling. As we described more fully in our other recent reviews, Nav-CLS in nodes with pumps proves sufficient to predict many of the pathological excitability phenomena reported for sick excitable cells. This review explains how the model came about and outlines how we have used it. Briefly, we direct the reader to studies in which Nav-CLS is being implemented in larger scale models of damaged excitable tissue. For those who might find it useful for teaching or research purposes, we coded the Nav-CLS/node of Ranvier model (with pumps) in NEURON. We include, here, the resulting "Regimes" plot of classes of excitability dysfunction.

Circles of care for people with intellectual and developmental disabilities: Communication, collaboration, and coordination.

OBJECTIVE: To review health information exchange (HIE) processes that affect the health of people with intellectual and developmental disabilities (IDD) and to suggest practical tips and strategies for communicating, collaborating, and coordinating in the primary care setting. SOURCES OF INFORMATION: The "Primary care of adults with intellectual and developmental disabilities. 2018 Canadian consensus guidelines" literature review and interdisciplinary input. MAIN MESSAGE: Disparities exist between the provision of health care for the general population and that for people with IDD. These disparities are due in part to gaps in HIE. Health information exchange involves documenting, collecting, and disseminating a patient's health information. In exploring ways to improve HIE for people with IDD, the communication skills of the family physician are considered in the context of the triad that includes the patient, his or her caregivers, and the family physician. The framework of the Patient's Medical Home is used in exploring these processes, and various strategies are offered for communicating, collaborating, and coordinating health care that can be implemented by family physicians in order to narrow the gaps in care that exist for people with IDD. CONCLUSION: Improvements in HIE by communicating, collaborating, and coordinating health care better will improve health outcomes for people with IDD.

Dissemination of a Child Passenger Safety Program Through Trauma Center-Community Partnerships.

Improper child passenger restraint use contributes to higher pediatric motor vehicle collision morbidity and mortality among cultural minority populations. Child passenger safety education improves caregiver knowledge of restraint use, but effective interventions require culturally specific programming. The purpose of this study was to evaluate the effectiveness of a child passenger safety education program culturally adapted through a pediatric trauma center's community partnerships. A nonexperimental observational cohort study using program evaluation data for the child passenger safety education programs during a 24-month period. Paired pretest/posttest self-reported survey responses measured changes in caregiver knowledge and self-efficacy of restraint use. Data were analyzed by class location and by caregiver language using a paired t test and Wilcoxon's signed ranks test. A total of 1,795 paired survey responses were collected in English, Spanish, or Russian. An increase in mean knowledge scores occurred overall, with a difference in mean of 0.565 (SE = 0.022, 95% CI [0.521, 0.607]). Stratification by class site and by language reflected significant increases in median scores, but findings were variable by study group. Pretest median scores for self-efficacy of restraint use were high for all groups, but the increases in posttest medians were also significant across groups (p ≤ .001). Caregiver knowledge and self-efficacy for child passenger restraint use increased after participation in the community classes. The pediatric trauma center's community partnerships facilitated uptake and adaption of the child passenger safety education programs and increased the injury prevention outreach to minority communities.

Membrane order parameters for interdigitated lipid bilayers measured via polarized total-internal-reflection fluorescence microscopy.

Incorporating ethanol in lipid membranes leads to changes in bilayer structure, including the formation of an interdigitated phase. We have used polarized total-internal-reflection fluorescence microscopy (pTIRFM) to measure the order parameter for Texas Red DHPE incorporated in the ethanol-induced interdigitated phase (LßI) formed from ternary lipid mixtures comprising dioleoylphosphatidylcholine, cholesterol and egg sphingomyelin or dipalmitoylphosphatidylcholine. These lipid mixtures have 3 co-existing phases in the presence of ethanol: liquid-ordered, liquid-disordered and LßI. pTIRFM using Texas Red DHPE shows a reversal in fluorescence contrast between the LßI phase and the surrounding disordered phase with changes in the polarization angle. The contrast reversal is due to changes in the orientation of the dye, and provides a rapid method to identify the LßI phase. The measured order parameters for the LßI phase are consistent with a highly ordered membrane environment, similar to a gel phase. An acyl-chain labeled BODIPY-FL-PC was also tested for pTIRFM studies of ethanol-treated bilayers; however, this probe is less useful since the order parameters of the interdigitated phase are consistent with orientations that are close to random, either due to local membrane disorder or to a mixture of extended and looping conformations in which the fluorophore is localized in the polar headgroup region of the bilayer. In summary, we demonstrate that order parameter measurements via pTIRFM using Texas Red-DHPE can rapidly identify the interdigitated phase in supported bilayers. We anticipate that this technique will aid further research in the effects of alcohols and other additives on membranes.

Right ventricular nitric oxide signaling in an ovine model of congenital heart disease: a preserved fetal phenotype.

We recently reported superior right ventricle (RV) performance in response to acute afterload challenge in lambs with a model of congenital heart disease with chronic left-to-right cardiac shunts. Compared with control animals, shunt lambs demonstrated increased contractility because of an enhanced Anrep effect (the slow increase in contractility following myocyte stretch). This advantageous physiological response may reflect preservation of a fetal phenotype, since the RV of shunt lambs remains exposed to increased pressure postnatally. Nitric oxide (NO) production by NO synthase (NOS) is activated by myocyte stretch and is a necessary intermediary of the Anrep response. The purpose of this study was to test the hypothesis that NO signaling is increased in the RV of fetal lambs compared with controls and shunt lambs have persistence of this fetal pattern. An 8-mm graft was placed between the pulmonary artery and aorta in fetal lambs (shunt). NOS isoform expression, activity, and association with activating cofactors were determined in fetal tissue obtained during late-gestation and in 4-wk-old juvenile shunt and control lambs. We demonstrated increased RNA and protein expression of NOS isoforms and increased total NOS activity in the RV of both shunt and fetal lambs compared with control. We also found increased NOS activation and association with cofactors in shunt and fetal RV compared with control. These data demonstrate preserved fetal NOS phenotype and NO signaling in shunt RV, which may partially explain the mechanism underlying the adaptive response to increased afterload seen in the RV of shunt lambs.

Stimulation-induced ectopicity and propagation windows in model damaged axons.

Neural tissue injuries render voltage-gated Na+ channels (Nav) leaky, thereby altering excitability, disrupting propagation and causing neuropathic pain related ectopic activity. In both recombinant systems and native excitable membranes, membrane damage causes the kinetically-coupled activation and inactivation processes of Nav channels to undergo hyperpolarizing shifts. This damage-intensity dependent change, called coupled left-shift (CLS), yields a persistent or "subthreshold" Nav window conductance. Nodes of Ranvier simulations involving various degrees of mild CLS showed that, as the system's channel/pump fluxes attempt to re-establish ion homeostasis, the CLS elicits hyperexcitability, subthreshold oscillations and neuropathic type action potential (AP) bursts. CLS-induced intermittent propagation failure was studied in simulations of stimulated axons, but pump contributions were ignored, leaving open an important question: does mild-injury (small CLS values, pumps functioning well) render propagation-competent but still quiescent axons vulnerable to further impairments as the system attempts to cope with its normal excitatory inputs? We probe this incipient diffuse axonal injury scenario using a 10-node myelinated axon model. Fully restabilized nodes with mild damage can, we show, become ectopic signal generators ("ectopic nodes") because incoming APs stress Na+ / K+ gradients, thereby altering spike thresholds. Comparable changes could contribute to acquired sodium channelopathies as diverse as epileptic phenomena and to the neuropathic amplification of normally benign sensory inputs. Input spike patterns, we found, propagate with good fidelity through an ectopically firing site only when their frequencies exceed the ectopic frequency. This "propagation window" is a robust phenomenon, occurring despite Gaussian noise, large jitter and the presence of several consecutive ectopic nodes.

Artificial intelligence for human gunshot wound classification.

Certain features are helpful in the identification of gunshot entrance and exit wounds, such as the presence of muzzle imprints, peripheral tears, stippling, bone beveling, and wound border irregularity. Some cases are less straightforward and wounds can thus pose challenges to an emergency room doctor or forensic pathologist. In recent years, deep learning has shown promise in various automated medical image classification tasks. This study explores the feasibility of using a deep learning model to classify entry and exit gunshot wounds in digital color images. A collection of 2418 images of entrance and exit gunshot wounds were procured. Of these, 2028 entrance and 1314 exit wounds were cropped, focusing on the area around each gunshot wound. A ConvNext Tiny deep learning model was trained using the Fastai deep learning library, with a train/validation split ratio of 70/30, until a maximum validation accuracy of 92.6% was achieved. An additional 415 entrance and 293 exit wound images were collected for the test (holdout) set. The model achieved an accuracy of 87.99%, precision of 83.99%, recall of 87.71%, and F1-score 85.81% on the holdout set. Correctly classified were 88.19% of entrance wounds and 87.71% of exit wounds. The results are comparable to what a forensic pathologist can achieve without other morphologic cues. This study represents one of the first applications of artificial intelligence to the field of forensic pathology. This work demonstrates that deep learning models can discern entrance and exit gunshot wounds in digital images with high accuracy.

Spontaneous excitation patterns computed for axons with injury-like impairments of sodium channels and Na/K pumps.

In injured neurons, "leaky" voltage-gated sodium channels (Nav) underlie dysfunctional excitability that ranges from spontaneous subthreshold oscillations (STO), to ectopic (sometimes paroxysmal) excitation, to depolarizing block. In recombinant systems, mechanical injury to Nav1.6-rich membranes causes cytoplasmic Na(+)-loading and "Nav-CLS", i.e., coupled left-(hyperpolarizing)-shift of Nav activation and availability. Metabolic injury of hippocampal neurons (epileptic discharge) results in comparable impairment: left-shifted activation and availability and hence left-shifted I(Na-window). A recent computation study revealed that CLS-based I(Na-window) left-shift dissipates ion gradients and impairs excitability. Here, via dynamical analyses, we focus on sustained excitability patterns in mildly damaged nodes, in particular with more realistic Gaussian-distributed Nav-CLS to mimic "smeared" injury intensity. Since our interest is axons that might survive injury, pumps (sine qua non for live axons) are included. In some simulations, pump efficacy and system volumes are varied. Impacts of current noise inputs are also characterized. The diverse modes of spontaneous rhythmic activity evident in these scenarios are studied using bifurcation analysis. For "mild CLS injury", a prominent feature is slow pump/leak-mediated E(Ion) oscillations. These slow oscillations yield dynamic firing thresholds that underlie complex voltage STO and bursting behaviors. Thus, Nav-CLS, a biophysically justified mode of injury, in parallel with functioning pumps, robustly engenders an emergent slow process that triggers a plethora of pathological excitability patterns. This minimalist "device" could have physiological analogs. At first nodes of Ranvier and at nociceptors, e.g., localized lipid-tuning that modulated Nav midpoints could produce Nav-CLS, as could co-expression of appropriately differing Nav isoforms.

Mothers and infants exposed to intimate partner violence compensate.

Reasons for the developmental variability in children exposed to intimate partner violence (IPV) are unclear and under studied. This article presents exploratory findings on (a) the potential impact of IPV on mother-child relationships and child development and (b) the association between these maternal-child relationship impacts and child development. The fit of findings with compensatory, spillover, and compartmentalization hypotheses was explored. Participants were 49 mothers and 51 children younger than 3 years of age affected by IPV. Data were collected on maternal-child interactions, child development, social support, difficult life circumstances, family functioning, child temperament, and parental depression. The findings suggested developmental impacts on children in the sample, along with children's high sensitivity and responsiveness to their caregivers. Although some spillover effects were observed, the predominant observation was of mothers and infants compensating for exposure to IPV in their interactions.

Factors that influence compliance for referral from primary care to hospital for maternal and neonatal complications in Bosaso, Somalia: a qualitative study.

OBJECTIVES: To estimate referral compliance and examine factors that influence decisions to comply with referral for newborn and maternal complications in Bosaso, Somalia. SETTING: Bosaso, Somalia, is a large port city that hosts a large proportion of internally displaced persons. The study was conducted at the only four primary health centres offering 24/7 delivery services and the only public referral hospital in Bosaso. PARTICIPANTS: All pregnant women who sought care at four primary centres and were referred to the hospital for maternal complications or mothers whose newborns were referred for neonatal complications were approached for enrolment from September to December 2019. In-depth interviews (IDIs) of 54 women and 14 healthcare workers (HCWs) were conducted. OUTCOME MEASURES: This study examined timely referral compliance from the primary centre to the hospital. IDIs were analysed for a priori themes investigating the decision-making process and experience of care for maternal and newborn referrals. RESULTS: Overall, 94% (n=51/54) of those who were referred, 39 maternal and 12 newborns, complied with the referral and arrived at the hospital within 24 hours. Of the three that did not comply, two delivered on the way, and one cited lack of money as the reason for noncompliance. Four themes emerged: trust in medical authority, cost of transportation and care, quality of care, and communications. The factors that facilitated compliance were the availability of transportation, family support, concern for health, and trust in medical authority. HCWs raised the importance of considering the maternal-newborn dyad throughout the referral process, and the need for official standard operating procedures for referrals including communications between the primary care and the hospital. CONCLUSIONS: High compliance for referral from primary to hospital care for maternal and newborn complications was observed in Bosaso, Somalia. Costs associated with transportation and care at the hospital need attention to motivate compliance.

Coupled left-shift of Nav channels: modeling the Na⁺-loading and dysfunctional excitability of damaged axons.

Injury to neural tissue renders voltage-gated Na⁺ (Nav) channels leaky. Even mild axonal trauma initiates Na⁺-loading, leading to secondary Ca²âº-loading and white matter degeneration. The nodal isoform is Nav1.6 and for Nav1.6-expressing HEK-cells, traumatic whole cell stretch causes an immediate tetrodotoxin-sensitive Na⁺-leak. In stretch-damaged oocyte patches, Nav1.6 current undergoes damage-intensity dependent hyperpolarizing- (left-) shifts, but whether left-shift underlies injured-axon Nav-leak is uncertain. Nav1.6 inactivation (availability) is kinetically limited by (coupled to) Nav activation, yielding coupled left-shift (CLS) of the two processes: CLS should move the steady-state Nav1.6 "window conductance" closer to typical firing thresholds. Here we simulated excitability and ion homeostasis in free-running nodes of Ranvier to assess if hallmark injured-axon behaviors--Na⁺-loading, ectopic excitation, propagation block--would occur with Nav-CLS. Intact/traumatized axolemma ratios were varied, and for some simulations Na/K pumps were included, with varied in/outside volumes. We simulated saltatory propagation with one mid-axon node variously traumatized. While dissipating the [Na⁺] gradient and hyperactivating the Na/K pump, Nav-CLS generated neuropathic pain-like ectopic bursts. Depending on CLS magnitude, fraction of Nav channels affected, and pump intensity, tonic or burst firing or nodal inexcitability occurred, with [Na⁺] and [K⁺] fluctuating. Severe CLS-induced inexcitability did not preclude Na⁺-loading; in fact, the steady-state Na⁺-leaks elicited large pump currents. At a mid-axon node, mild CLS perturbed normal anterograde propagation, and severe CLS blocked saltatory propagation. These results suggest that in damaged excitable cells, Nav-CLS could initiate cellular deterioration with attendant hyper- or hypo-excitability. Healthy-cell versions of Nav-CLS, however, could contribute to physiological rhythmic firing.

The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.

Duchenne muscular dystrophy (DMD) is an X-linked dystrophin-minus muscle-wasting disease. Ion homeostasis in skeletal muscle fibers underperforms as DMD progresses. But though DMD renders these excitable cells intolerant of exertion, sodium overloaded, depolarized, and spontaneously contractile, they can survive for several decades. We show computationally that underpinning this longevity is a strikingly frugal, robust Pump-Leak/Donnan (P-L/D) ion homeostatic process. Unlike neurons, which operate with a costly "Pump-Leak-dominated" ion homeostatic steady state, skeletal muscle fibers operate with a low-cost "Donnan-dominated" ion homeostatic steady state that combines a large chloride permeability with an exceptionally small sodium permeability. Simultaneously, this combination keeps fiber excitability low and minimizes pump expenditures. As mechanically active, long-lived multinucleate cells, skeletal muscle fibers have evolved to handle overexertion, sarcolemmal tears, ischemic bouts, etc.; the frugality of their Donnan dominated steady state lets them maintain the outsized pump reserves that make them resilient during these inevitable transient emergencies. Here, P-L/D model variants challenged with DMD-type insult/injury (low pump-strength, overstimulation, leaky Nav and cation channels) show how chronic "nonosmotic" sodium overload (observed in DMD patients) develops. Profoundly severe DMD ion homeostatic insult/injury causes spontaneous firing (and, consequently, unwanted excitation-contraction coupling) that elicits cytotoxic swelling. Therefore, boosting operational pump-strength and/or diminishing sodium and cation channel leaks should help extend DMD fiber longevity.

Anomalous papillary muscles-Implications in the surgical treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: To categorize and assess the functional significance of anomalous papillary muscles in patients undergoing surgical management of obstructive hypertrophic cardiomyopathy. METHODS: We reviewed the records of operations for obstructive hypertrophic cardiomyopathy and identified 73 patients with an anomalous papillary muscle. Anomalous papillary muscles inserting directly into the body of the anterior mitral valve leaflet were classified as type I, those with both direct insertion into the body of the leaflet and attachment to the free edge of the anterior leaflet were categorized as type II, and anomalous papillary muscles inserting into the free edge of the anterior leaflet were grouped as type III. Additionally, we investigated detection rates by preoperative transthoracic echocardiography, intraoperative transesophageal echocardiography, and cardiac magnetic resonance imaging. RESULTS: The mean age of patients was 51.9 ± 12.3 years, and 49.3% were male. The anomalous papillary muscle was classified as type I in 31.5% of patients, type II in 35.6%, and type III in 32.9%. Only type I and type II anomalous papillary muscles contributed to left ventricular outflow tract obstruction. The anomalous papillary muscle was detected on preoperative transthoracic echocardiography in 11% of patients and by intraoperative transesophageal echocardiography in 27.4% of patients. No anomalous papillary muscles were identified on cardiac magnetic resonance imaging. All patients underwent septal myectomy with or without (n = 34) associated excision of the anomalous papillary muscle. Excision of the papillary muscles was more common in patients with type I and II (76.4% and 80.8%, respectively) when compared with type III (4.2%). Ten patients underwent mitral valve repair, and 1 patient had mitral valve replacement. CONCLUSIONS: Papillary muscle abnormalities are important findings in patients with obstructive hypertrophic cardiomyopathy but are not identified preoperatively in the majority of patients. Recognition of anomalous papillary muscles intraoperatively and understanding of the morphologic subtypes are critical to adequate gradient relief and preservation of mitral valve function. The optimum approach involves a transaortic extended septal myectomy associated with the resection of the anomalous papillary muscles in patients with type I and II anatomy.

Immediate Postpartum Long-Acting Reversible Contraception: A Comparison Across Six Humanitarian Country Contexts.

Postpartum family planning (FP) could prevent more than 30% of maternal deaths by effectively spacing births; this is particularly relevant in humanitarian contexts given that disproportionate maternal death occurs in countries affected by crises. In humanitarian settings, where accessing functional facilities is challenging with security risks that constrain movement, many women are unable to return for their 6-week postpartum visits and thus unable to receive FP counseling and adopt a method that suits their fertility intentions. Thus, immediate postpartum family planning (IPPFP) interventions, focused on long-acting reversible contraception (LARC) and tailored toward humanitarian contexts, could contribute to healthy timing and spacing of pregnancy, particularly among postpartum women, and improve maternal and newborn health. In 2014, Save the Children integrated postpartum intrauterine device (IUD) services into its FP package in emergency settings. In 2017, this expanded to include postpartum implant uptake as well, given updated World Health Organization guidelines. Three countries (Democratic Republic of Congo, Somalia, and Pakistan) opted for higher-intensity programming for IPPFP with a specific focus on LARC. This involved training delivery-room providers on counseling and provision of IPPFP, as well as training antenatal care nurses in counseling pregnant women on IPPFP options. Three countries (Rwanda, Syria, and Yemen) did not implement notable IPPFP interventions, although they provided the standard of care and monitored provision via monthly service delivery data. Using data from 2016 to 2019, we examined trends in immediate postpartum LARC (IPP LARC) uptake and compared countries with higher-intensity IPP LARC interventions to countries providing standard care. Tests of association were performed to assess the significance of these differences. In the country programs with higher-intensity IPPFP interventions, IPP LARC as a percentage of all deliveries was much higher overall during the July 2016-December 2019 period. The IPP LARC intervention had a significant impact on the overall proportion of women and girls who adopted an IUD or implant within the first 48 h of delivery, F (1, 250) = 523.16, p < 0.001. The mean percentage of IPP LARC among all deliveries in intervention country programs was 10.01% as compared to 0.77% in countries providing standard care. Results suggest that there is demand for IPP LARC in humanitarian contexts and that uptake increases when multipronged solutions focusing on provider training, community outreach, and service integration are applied.

HIF-1α promotes cellular growth in lymphatic endothelial cells exposed to chronically elevated pulmonary lymph flow.

Normal growth and development of lymphatic structures depends on mechanical forces created by accumulating interstitial fluid. However, prolonged exposure to pathologic mechanical stimuli generated by chronically elevated lymph flow results in lymphatic dysfunction. The mechanisms that transduce these mechanical forces are not fully understood. Our objective was to investigate molecular mechanisms that alter the growth and metabolism of isolated lymphatic endothelial cells (LECs) exposed to prolonged pathologically elevated lymph flow in vivo within the anatomic and physiologic context of a large animal model of congenital heart disease with increased pulmonary blood flow using in vitro approaches. To this end, late gestation fetal lambs underwent in utero placement of an aortopulmonary graft (shunt). Four weeks after birth, LECs were isolated and cultured from control and shunt lambs. Redox status and proliferation were quantified, and transcriptional profiling and metabolomic analyses were performed. Shunt LECs exhibited hyperproliferative growth driven by increased levels of Hypoxia Inducible Factor 1α (HIF-1α), along with upregulated expression of known HIF-1α target genes in response to mechanical stimuli and shear stress. Compared to control LECs, shunt LECs exhibited abnormal metabolism including abnormalities of glycolysis, the TCA cycle and aerobic respiration. In conclusion, LECs from lambs exposed in vivo to chronically increased pulmonary lymph flow are hyperproliferative, have enhanced expression of HIF-1α and its target genes, and demonstrate altered central carbon metabolism in vitro. Importantly, these findings suggest provocative therapeutic targets for patients with lymphatic abnormalities.

Strengthening Health Systems in Humanitarian Settings: Multi-Stakeholder Insights on Contraception and Postabortion Care Programs in the Democratic Republic of Congo and Somalia.

Background: In humanitarian settings, strengthening health systems while responding to the health needs of crisis-affected populations is challenging and marked with evidence gaps. Drawing from a decade of family planning and postabortion care programming in humanitarian settings, this paper aims to identify strategic components that contribute to health system strengthening in such contexts. Materials and Methods: A diverse range of key informants from North Kivu (Democratic Republic of Congo, DRC) and Puntland (Somalia), including female and male community members, adolescents and adults, healthcare providers, government and community leaders, participated in qualitative interviews, which applied the World Health Organization health system building blocks framework. Data were thematically analyzed according to this framework. Results: Findings from the focus group discussions (11 in DRC, 7 in Somalia) and key informant interviews (seven in DRC, four in Somalia) involving in total 54 female and 72 male participants across both countries indicate that health programs in humanitarian settings, such as Save the Children's initiative on family planning and postabortion care, could contribute to strengthening health systems by positively influencing national policies and guidance, strengthening local coordination mechanisms, capacitating the healthcare workforce with competency-based training and supportive supervision (benefiting facilities supported by the project and beyond), developing the capacity of Ministry of Health staff in the effective management of the supply chain, actively and creatively mobilizing the community to raise awareness and create demand, and providing quality and affordable services. Financial sustainability is challenged by the chronically limited healthcare expenditure experienced in both humanitarian contexts. Conclusions: In humanitarian settings, carefully designed healthcare interventions, such as those that address the family planning and postabortion care needs of crisis-affected populations, have the potential not only to increase access to essential services but also contribute to strengthening several components of the health system while increasing the government capacity, ownership, and accountability.