Predictors of under-five healthcare utilization in Rongo sub-county of Migori County, Kenya: results of a population-based cross-sectional survey.

Introduction: to achieve the sustainable development goal for child survival, we must better understand the socioeconomic characteristics, household behaviors and access to community health services which predict care utilization for children. This study assessed predictors of health care utilization for children under five in Migori County, Kenya. Methods: we used multivariable logistic regression in the context of an integrated health intervention which employed paid, trained, and supervised community health workers (CHWs), inclusive of traditional birth attendants (TBAs). The intervention was delivered with Ministry of Health in one of five geographies included in the study. Results: community health workers (CHW) home visits were associated with a two-fold increase in care seeking for children with respiratory symptoms. Following implementation of a CHW-led malaria intervention, the use of malaria rapid diagnostic tests increased, while fever prevalence decreased. Households in the intervention area were three times more likely to seek care for their child´s fever. Increased care utilization for children with fever was positively associated with male partner attendance at antenatal care visits and negatively associated with skilled delivery and recognition of warning signs. Care utilization for respiratory symptoms was positively associated with caregiver education and negatively associated with household size. Care utilization for diarrhea was positively associated with having a recent under-five death in the household. Conclusion: the study suggests that trained and motivated CHWs may be an effective tool for improving care utilization for children. Further, the study builds on evidence of male partner involvement and caregiver education as predictors of child care utilization.

Preoperative Radioactive Seed Localization for Nonpalpable Breast Lesions: Technique, Pitfalls, and Solutions.

Iodine 125 ((125)I) radioactive seed localization has emerged as a reliable and safe alternative to wire localization for guidance during the surgical resection of nonpalpable breast lesions. The breast imager has a responsibility to be familiar with the general principles of this evolving technique, including its advantages and disadvantages as well as the technical differences involved in placement of seeds versus traditional wire localization. Although placement of (125)I seeds is conceptually similar to wire placement, there are additional technical considerations and safety measures that need to be addressed and implemented when radioactive seeds are used. We draw from our experience with more than 1000 cases of radioactive seed localization since inception of our program in 2009 to provide illustrative examples of not only the proper technique of radioactive seed localization, but also mishaps that may occur during this procedure, along with practical suggestions to prevent these problems. We examine some of the difficulties that we have encountered during radioactive seed localization at our institution, including bone wax mimicking the seed, the inadvertent deployment of seeds, the need for multiple seeds or supplemental wires, problematic seed locations, and difficulty in surgical retrieval of the seed. Recognizing the potential pitfalls of radioactive seed localization and understanding the appropriate guidelines and precautions for the safe, secure handling and placement of radioactive seeds is essential for a successful radioactive seed localization program.

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function.

Effect of N-acetyl-l-cysteine on insulin resistance caused by prolonged free fatty acid elevation.

Circulating free fatty acids (FFAs) are elevated in obesity and cause insulin resistance. The objective of the current study was to determine whether the antioxidant N-acetyl-l-cysteine (NAC) prevented hepatic and peripheral insulin resistance caused by prolonged elevation of plasma FFAs. Chronically cannulated Wistar rats received saline (SAL), Intralipid plus heparin (IH), IH plus NAC, or NAC i.v. infusion for 48 h. Insulin sensitivity was determined using the hyperinsulinemic-euglycemic clamp with tritiated glucose tracer. IH induced hepatic and peripheral insulin resistance (P<0.05). NAC co-infusion did not prevent insulin resistance in the liver, although it was able to prevent peripheral insulin resistance. Prolonged IH infusion did not appear to induce oxidative stress in the liver because hepatic content of protein carbonyl, malondialdehyde, and reduced to oxidized glutathione ratio did not differ across treatment groups. In alignment with our insulin sensitivity results, IH augmented skeletal muscle protein carbonyl content and this was prevented by NAC co-infusion. Taken together, our results indicate that oxidative stress mediates peripheral, but not hepatic, insulin resistance resulting from prolonged plasma FFA elevation. Thus, in states of chronic plasma FFA elevation, such as obesity, antioxidants may protect against peripheral but not hepatic insulin resistance.

stathmin, a gene enriched in the amygdala, controls both learned and innate fear.

Little is known about the molecular mechanisms of learned and innate fear. We have identified stathmin, an inhibitor of microtubule formation, as highly expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical structures that send information to the LA about the conditioned (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP). The knockout mice also exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments. By contrast, these mice do not show deficits in the water maze, a spatial task dependent on the hippocampus, where stathmin is not normally expressed. We therefore conclude that stathmin is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear.