Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Comparative development of limb musculature in phylogenetically and ecologically divergent lizards.

BACKGROUND: Squamate reptiles (lizards, snakes, and amphisbaenians) exhibit incredible diversity in their locomotion, behavior, morphology, and ecological breadth. Although they often are used as models of locomotor diversity, surprisingly little attention has been given to muscle development in squamate reptiles. In fact, the most detailed examination was conducted almost 80 years ago and solely focused on the proximal limb regions. Herein, we present forelimb and hindlimb muscle morphogenesis data for three lizard species with different locomotion and feeding strategies: the desert grassland whiptail lizard, the central bearded dragon, and the veiled chameleon. This study fills critical gaps in our understanding of muscle morphogenesis in squamate reptiles and presents a comparative and temporospatial analysis of muscle development. RESULTS: Our results reveal a conserved pattern of early muscle development among lizards with different adult morphologies and ecologies. The variations that exist are concentrated in distal regions, particularly the specialized autopodia of chameleons, where differentiation of muscles associated with the digits is delayed. CONCLUSIONS: The chameleon autopod provides an example of major evolutionary modifications to the skeleton with only minor disruption of the conserved order and pattern of limb muscle development. This robustness of muscle patterning facilitates the evolution of extreme yet functional phenotypes.

Survival Outcomes in Men with Unfavorable Intermediate-Risk and High-Risk Prostate Cancer Treated with Prostate-Only versus Whole Pelvic Radiation Therapy.

PURPOSE: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy. Treatment is frequently intensified by electively treating the pelvic lymph nodes (LNs) with whole pelvis radiotherapy (WPRT), but practice patterns and the benefits of WPRT are not well defined. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy. MATERIALS AND METHODS: National Cancer Database records of men diagnosed between 2008-2015 with UIR-PCa or HR-PCa and treated with prostate EBRT±androgen deprivation therapy (72-86.4 Gy) with (15,175) or without (13,549) WPRT were reviewed. Risk of LN involvement was calculated using the Memorial Sloan Kettering Cancer Center nomogram. Measured confounders were balanced with inverse probability of treatment weighting and OS hazard ratios (HRs) were generated using multivariable Cox regression. RESULTS: Of the men, 53% received WPRT. Every 1% increase in risk of LN involvement correlated with a 1% increase in risk of death (p <0.001). WPRT trended toward improved OS in all men with UIR-PCa and HR-PCa (HR: 0.95 [95% CI: 0.90-1.006], p=0.055). WPRT correlated with improved OS in men with Gleason 9 and 10 disease (HR: 0.87 [0.78-0.98], p=0.02) or risk of LN involvement ≥10% (HR: 0.93 [0.87-0.99], p=0.03). CONCLUSIONS: Men with higher LN risk scores and Gleason grade benefited from WPRT. These results complement the recent POP-RT randomized trial in mostly positron emission tomography/computerized tomography-staged patients, demonstrating that a more heterogeneous population of men staged without functional imaging benefits from WPRT.

A Coastal Vulnerability Framework to Guide Natural Infrastructure Funds Allocation in Compressed Time.

Hurricane Maria, a category 4 tropical cyclone, hit the US non-incorporated territory of Puerto Rico on September 20, 2017. Widespread physical and natural infrastructure damage was observed, especially in already vulnerable coastal communities. As public sector funding availability for natural infrastructure (ex. coastal ecosystems) increases, mechanisms for its efficient and equitable allocation are lacking. An accessible and replicable coastal vulnerability indicator framework is presented to assist state and federal policy makers in the allocation of funding for coastal natural infrastructure recovery. To assess funding priorization gaps and test the applicability of the proposed framework, spatial patterns in the estimated funding need identified in state-led post-Hurricane Maria assessments for natural infrastructure rehabilitation efforts were compared to physical and social coastal vulnerability estimations. Three main challenges that emerge during the implementation of a vulnerability indicator framework were considered for its design: (1) the compressed time frame in which decisions are made after an extreme weather event, (2) the availability of data to calculate indicators in a reduced time frame, and (3) the accessibility of results to a broad variety of stakeholders. We propose a vulnerability indicator framework that can become operational in a relatively short period of time, attempts to simplify data gathering efforts, and uses methods that aim to be more transparent and understandable to a broad group of stakeholders.

Dasatinib-induced Chylothorax in Chronic Myelogenous Leukemia in Pediatric Patient: Report of a Case and Review of Literature.

Dasatinib is a second-generation potent and efficacious oral tyrosine kinase inhibitor frequently used for imatinib-resistant or intolerant BCR-ABL-positive chronic myeloid leukemia and for Philadelphia chromosome-positive acute lymphocytic leukemia. Dasatinib is known to cause adverse pulmonary events such as chylothorax and has been described in the adult literature but not pediatric literature. The authors present a pediatric case of dasatinib-related chylothorax, subsequent management, and a review of the literature of adult cases with dasatinib-related chylothorax.

Synthesis of purines and adenines containing the hexafluoroisopropyl group.

Several new derivatives of adenine, purine, and theophylline containing the (CF3)2CH group connected to a nitrogen atom of the imidazole ring were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated products in 47-78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the formation of a new derivative of caffeine.

Quantum confinement in few layer SnS nanosheets.

Orthorhombic tin monosulfide (SnS) consists of layers of covalently bound Sn and S atoms held together by weak van der Waals forces and is a stable two-dimensional material with potentially useful properties in emerging applications such as valleytronics. Large-scale sustainable synthesis of few-layer (e.g., 1-10 layers) SnS is a challenge, which also slows progress in understanding their properties as a function of number of layers. Herein we describe solvothermal synthesis of SnS in water or ethylene glycol. The latter yields a flower-like morphology where the petals are SnS nanoplates and sonication and separation of these flowers via differential centrifugation yields 1-10 layer SnS nanoplates. The direct optical absorption edges of these SnS nanoplates blue-shift due to quantum confinement from 1.33 to 1.88 eV as the thickness (number of layers) is decreased from ∼5 nm (10 layers) to ∼2 nm (4 layers).

Modern Day Bicruciate-Retaining Total Knee Arthroplasty: A Short-Term Review of 146 Knees.

BACKGROUND: Bicruciate retaining (BCR) implants were first proposed in the 1960s with the polycentric knee. Given the technical difficulty of implanting these devices, and the mixed results at the time, the BCR concept had stalled, until recently. This study seeks to provide a short-term review of the BCR implant design, describe patient-reported outcomes, and discuss key aspects to ensure successful implantation of the modern-day BCR implant design. METHODS: Between October 2014 and December 2016, the senior author performed 146 primary total knee arthroplasties using BCR implants. Arthritic knees, with minimal soft tissue damage and an intact anterior cruciate ligament, were the general indications used for this cohort. All patients implanted with the BCR device were included in this analysis. One hundred forty-six (100%) BCR knees were available for follow-up at an average of 12 months (range, 1-33 months) postoperatively. RESULTS: Ninety-one percent of respondents reported their knee always or sometime feels normal, with only 9% of respondents reporting their knee never feels normal. Our study reports 94% of patients reported neutral satisfaction or higher, with only 6% of patients reporting dissatisfaction and 1% reported being very dissatisfied. Of all 146 BCR devices implanted, there were 2 (1.4%) revisions and 1 (0.7%) reoperation, a manipulation under anesthesia. CONCLUSION: This is the largest consecutive series of BCR total knee arthroplasties using the modern-day implant design with 1-year follow-up in the United States. The results of our study show great patient-reported satisfaction, function, and short-term outcomes for patients implanted with the new BCR design.

Inhibition of Listeria monocytogenes in Fresh Cheese Using Chitosan-Grafted Lactic Acid Packaging.

A chitosan from biologically obtained chitin was successfully grafted with d,l-lactic acid (LA) in aqueous media using p-toluenesulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy, water vapor permeability, and relative humidity (RH) losses. Additionally, the grafting in chitosan with LA produced films with improved mechanical properties. This material successfully extended the shelf life of fresh cheese and inhibited the growth of Listeria monocytogenes during 14 days at 4 °C and 22% RH, whereby inoculated samples with chitosan-g-LA packaging presented full bacterial inhibition. The results were compared to control samples and commercial low-density polyethylene packaging.

Hypothyroidism.

On the basis of strong clinical evidence, congenital hypothyroidism should be identified and treated early to avoid potentially profound cognitive deficits. On the basis of strong clinical evidence, the dose of levothyroxine is higher at early ages and progressively decreases into adulthood. On the basis of observational studies and consensus, children with congenital hypothyroidism and a eutopic thyroid gland should discontinue levothyroxine treatment at age 3 years to determine whether their hypothyroidism was transient. On the basis of observational studies, most patients with Hashimoto thyroiditis present with a goiter and without hypothyroidism. On the basis of observational studies, subclinical hypothyroidism is more common among obese children. On the basis of strong clinical evidence, children with central hypothyroidism should have other pituitary hormone deficiencies ruled out.

Ultrasound assessment of peripheral intravenous catheters by nurses in the pediatric intensive care unit.

OBJECTIVE: Establish the feasibility of pediatric intensive care unit (PICU) nurse-directed ultrasound assessment (UA) of peripheral intravenous (PIV) catheters, compare the results of UA to traditional assessment (TA), and determine PIV survival after UA. DESIGN: Prospective observational cohort study. SETTING: PICU within a children's hospital. PATIENTS: PICU patients with a PIV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight nurses performed UA on 131 PIVs in 85 patients. Median age was 3.0 years (IQR 1.0-13.8) and median weight was 15.0 kg (IQR 9.6-59.3). The most common PIV location was the arm (43%) and extravasation occurred in 15% of PIVs. Agreement between TA and UA was moderate with a Kappa of 0.47 (95% CI 0.28-0.66). Nursing confidence in the UA was significantly higher than TA (92% vs 21% very confident, p < 0.0001). In 106 PIVs with a UA that indicated the PIV was intravascular (i.e. negative UA), the median survival was 50.0 h (IQR 21.8-100.3). CONCLUSIONS: Nurses can perform UA of PIV status in PICU patients and express greater confidence in the findings of UA than TA. Further study is necessary to determine the impact of UA on the rate of PIV complications.

How do Central American Parents in the United States View the Importance of and Obtain Information About Behaviors Associated with the Risk of Early Childhood Obesity?

Background: Data suggest that Latinx preschool-age children are at increased risk of obesity. The fastest-growing Latinx population in the United States originates from El Salvador, Guatemala, and Honduras, also known as the Northern Triangle countries. Purpose: To describe how Central American parents from the Northern Triangle countries perceive the importance of energy balance-related behaviors (EBRBs), their preferred sources to obtain information about EBRBs, and to assess whether these differ by parent's gender and country of the nativity. Methods: Cross-sectional survey. Results: Seventy-four parents with at least one child between 2 and 5 years of age participated in the study. More than half were immigrants from El Salvador, Guatemala, and Honduras and were classified as having low acculturation. Mothers perceived consuming >5 fruits and vegetables daily, limiting sugar-sweetened beverages consumption, and having <2 hours daily screen time as extremely important, whereas fathers perceived these behaviors as being less important. Although a higher proportion of foreign-born than US-born parents perceived most of the assessed EBRBs (4 out of 6) as extremely important, these differences were not significant. Parents reported multiple sources to obtain EBRB-related information. Direct person-to-person interactions were the most commonly preferred sources, with pediatricians being the top source (97.3%), followed by other parents (86.5%), and WIC professionals (74.3%). Pediatricians were the preferred source to obtain information about EBRBs, irrespective of parent's gender and country of the nativity. A higher proportion of US-born than foreign-born parents reported a preference to obtain EBRB-related information from other parents. Conclusions: Findings suggest the significance of understanding how Central American parents perceive the importance of EBRBs and the sources they would prefer to obtain information for their children's EBRBs. Study findings have implications for health education and obesity prevention interventions designed to reach and deliver key evidence-based child health information to Central American parents from the Northern Triangle countries in the United States.

Improving Pediatric Intensive Care Unit Discharge Timeliness of Infants with Bronchiolitis Using Clinical Decision Support.

BACKGROUND: Identifying children ready for transfer out of the pediatric intensive care unit (PICU) is an area that may benefit from clinical decision support (CDS). We previously implemented a quality improvement (QI) initiative to accelerate the transfer evaluation of non-medically complex PICU patients with viral bronchiolitis receiving floor-appropriate respiratory support. OBJECTIVES: Design a CDS tool adaptation of this QI initiative to further accelerate transfer evaluation of appropriate patients. METHODS: The original initiative focused on identifying for transfer evaluation otherwise healthy children admitted to the PICU with bronchiolitis who had been receiving floor-appropriate levels of respiratory support for at least 6 hours. However, this initiative required that clinicians manually track the respiratory support of qualifying patients. We designed an electronic health record (EHR)-based CDS tool to automate identification of transfer-ready candidates. The tool parses EHR data to identify children meeting prior QI initiative criteria and alerts clinicians to assess transfer readiness once a child has been receiving floor-appropriate respiratory support for 6 hours. We compared time from reaching floor-appropriate support to placement of the transfer order ("time-to-transfer"), PICU length of stay (LOS), and hospital LOS between patients admitted prior to our QI initiative (December 1, 2018-October 19, 2019, "pre-QI phase"), during the initiative but before CDS tool implementation (October 20, 2019-February 7, 2022, "QI phase"), and after CDS implementation (February 8-November 11, 2022, "CDS phase"). RESULTS: CDS-phase patients (n = 131) had a shorter median time-to-transfer of 5.23 (interquartile range [IQR], 3.38-10.0) hours compared with QI-phase patients (n = 304) at 5.93 (IQR, 4.23-12.2) hours (p = 0.04). PICU and hospital LOS values decreased from the pre-QI (n = 150) to QI phase. Though LOS reductions were sustained during the CDS phase, further reductions from QI to CDS phase were not statistically significant. CONCLUSION: An EHR-based CDS adaptation of a prior QI initiative facilitated timely identification of PICU patients with bronchiolitis ready for transfer evaluation. Such tools might allow PICU clinicians to focus on other high-acuity tasks while accelerating transfer evaluation of appropriate patients.

Tumor Syndromes: Neurosurgical Evaluation and Management.

There are multiple syndromes associated with tumors of the central nervous system (CNS). The most common CNS tumor syndrome is neurofibromatosis-1, with well-defined major and minor criteria needed for diagnosis. Other syndromes with variable degree of CNS and extra-CNS involvement that the neurosurgeon should be aware of include neurofibromatosis-2; Turcot syndrome; Cowden syndrome; Gorlin syndrome; Li-Fraumeni syndrome; ataxia-telangiectasia; multiple endocrine neoplasia type 1; von Hippel-Lindau syndrome; and tuberous sclerosis complex. Although most CNS tumor syndromes follow an autosomal dominant pattern of inheritance, the genetic underpinnings of each disease are complex and increasingly better understood.

Central American Parents' Preferences for Content and Modality for a Family-Centered Intervention to Promote Healthful Energy Balance-Related Behaviors of Their Preschool-Age Children.

This formative research used a cross-sectional survey to assess interest in informational content and intervention modalities for the design of an early childhood obesity prevention intervention for Central American families from the Northern Triangle countries (El Salvador, Guatemala, and Honduras) living in the United States. A total of 74 parents (36 mothers, 38 fathers) with a mean age of 31.6 years (SD = 5.6) completed the survey; 59.5% of whom were born outside of the United States. Although most parents reported being very interested in receiving information related to the seven assessed energy balance-related behaviors, there were significant differences by parents' gender and nativity. Most parents endorsed remote modalities for content delivery via text/SMS, WhatsApp, and e-mail. However, respondents were also receptive to in-person delivery provided by community health workers. There were also significant differences in parents' preferences for intervention modalities by parents' gender and nativity. Future steps should include investigating different intervention modalities and their integration into a linguistic and culturally sensitive family-based intervention to promote healthful energy balance-related behaviors of preschool-age children in Central American families originating from the Northern Triangle countries.

The time is now: Student-driven implementation of social justice and anti-racism focused curricula in medical scientist training program education.

There exists a dearth of supplementary programs to educate physician-scientist trainees on anti-racism and topics surrounding social justice in medicine and science. Education on these topics is critical to prevent the perpetuation of systemic racism within the institutions of academia and medicine. Students in the Washington University School of Medicine Medical Scientist Training Program and the Tri-Institutional MD-PhD Program developed journal clubs with curricula focused on social justice and anti-racism for the summer of 2020. In this article, we describe the impact of the Washington University journal club on the education of first year MD-PhD students and summarize the progress to date. The role of the journal club in the midst of the "double pandemic" of COVID-19 and generational systemic racism is discussed, highlighting the need for such supplemental curricula in MD-PhD programs nation-wide.

77Se NMR Probes the Protein Environment of Selenomethionine.

Sulfur is critical for the correct structure and proper function of proteins. Yet, lacking a sensitive enough isotope, nuclear magnetic resonance (NMR) experiments are unable to deliver for sulfur in proteins the usual wealth of chemical, dynamic, and structural information. This limitation can be circumvented by substituting sulfur with selenium, which has similar physicochemical properties and minimal impact on protein structures but possesses an NMR compatible isotope (77Se). Here we exploit the sensitivity of 77Se NMR to the nucleus' chemical milieu and use selenomethionine as a probe for its proteinaceous environment. However, such selenium NMR spectra of proteins currently resist a reliable interpretation because systematic connections between variations of system variables and changes in 77Se NMR parameters are still lacking. To start narrowing this knowledge gap, we report here on a biological 77Se magnetic resonance data bank based on a systematically designed library of GB1 variants in which a single selenomethionine was introduced at different locations within the protein. We recorded the resulting isotropic 77Se chemical shifts and relaxation times for six GB1 variants by solution-state 77Se NMR. For four of the GB1 variants we were also able to determine the chemical shift anisotropy tensor of SeM by solid-state 77Se NMR. To enable interpretation of the NMR data, the structures of five of the GB1 variants were solved by X-ray crystallography to a resolution of 1.2 Å, allowing us to unambiguously determine the conformation of the selenomethionine. Finally, we combine our solution- and solid-state NMR data with the structural information to arrive at general insights regarding the execution and interpretation of 77Se NMR experiments that exploit selenomethionine to probe proteins.

Who, what, where, when, and why: demographic and ecological factors contributing to hostile school climate for lesbian, gay, bisexual, and transgender youth.

This study examines how locational (region and locale), community-level (school district poverty and adult educational attainment), and school district-level (district size and ratios of students to key school personnel) variables are related to indicators of hostile school climate for lesbian, gay, bisexual, and transgender (LGBT) youth. Indicators of hostile climate included frequency of homophobic remarks and victimization regarding sexual orientation and gender expression. We used data from a national survey of LGBT secondary school students (N = 5,420; 57.6% female; 65.5% White; mean age = 15.9). Results from regression analyses demonstrated that LGBT youth in rural communities and communities with lower adult educational attainment may face particularly hostile school climates. School district characteristics contributed little to the variation in LGBT youth's experiences. Findings highlight the importance of considering the multiple contexts that LGBT youth inhabit, particularly as they pertain to educational experiences.