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Background: HIV clinical guidelines recommend hypertension detection and management to lower cardiovascular disease risk, but these have not been effectively implemented for people living with HIV (PWH). Addressing this implementation gap requires community-engaged implementation studies focused on addressing implementation barriers specific to the HIV care context., Methods: This protocol describes a type 2 effectiveness-implementation hybrid study conducted in nine primary care clinics in Johannesburg. The study will evaluate the effect of implementation strategies on guideline-recommended blood pressure assessment and management in HIV clinics and the effects of assessment/management on patient blood pressure. A stepped-wedge, cluster randomized study design was used to randomize clinics to the time at which they receive the implementation strategies and patient intervention. The implementation strategies tested include identifying and preparing care champions, changing record systems, conducting ongoing training, providing audit and feedback, and changing the physical structure/equipment. The patient intervention tested includes detection of elevated blood pressure, educational materials, lifestyle modification advice, and medication where needed. Implementation outcomes include adoption, fidelity (co-primary outcome), cost, and maintenance of the blood pressure assessment protocol in participating clinics, while patient outcomes include reach, effectiveness (co-primary outcome), and long-term effects of the intervention on patient blood pressure. These will be assessed via direct observation, study records, staff logs, medical chart reviews, and patient and healthcare worker surveys. To examine effects on the implementation (intervention fidelity) and effectiveness (patient blood pressure changes) co-primary outcomes, we will use the standard Hussey and Hughes model for analysis of stepped-wedge designs which includes fixed effects for both interventions and time periods, and a random effect for sites. Finally, we will examine the costs for the implementation strategies, healthcare worker time, and patient-facing intervention materials, as well as the cost-effectiveness and cost-utility of the intervention using study records, patient surveys, and a time and motion assessment., Discussion: This study will address knowledge gaps around implementation of cardiovascular disease preventive practices in HIV care in South Africa. In doing so, it will provide a dual opportunity to promote evidence-based care in the South African HIV care context and help refine implementation research methods to better serve HIV populations globally., Trial Registration: ClinicalTrials.gov: NCT05846503. Registered on May 6, 2023. https://classic., Clinicaltrials: gov/ct2/show/NCT05846503 ., (© 2024. The Author(s).)

Introduction: Older trauma patients are at risk for worse outcomes compared to younger patients. We hypothesized that early initiation of palliative care (EPC) evaluations, within 72 h of trauma intensive care unit (ICU) admission, would be associated with reduced invasive procedures without a change in hospital mortality., Methods: A retrospective cohort review was performed of all trauma patients aged ≥65 y admitted to the trauma (ICU) from January 1, 2016, to December 31, 2021. Patients who received formal palliative care assessments were included. Patient demographics and injury characteristics were evaluated. The primary outcome was ICU length of stay (LOS). Secondary outcomes included code status change, tracheostomy or percutaneous endoscopic gastrostomy placement, use and length of mechanical ventilation, in-hospital mortality, and withdrawal of life-sustaining care., Results: Two hundred twenty-five patients met inclusion. One hundred and six had EPC while 119 had late palliative care. EPC was associated with decreased ICU LOS (3 versus 9 d, P < 0.001), hospital LOS (3 versus 11 d, P < 0.001), and days on mechanical ventilation (P < 0.001), and fewer tracheostomy (P = 0.007) and percutaneous endoscopic gastrostomy tubes (P = 0.049). There was no difference in withdrawal of life-sustaining care (P = 0.581) or in-hospital mortality (P = 0.172). Pre-existing code status or code status clarification early in admission was associated with EPC (P = 0.003) and decreased interventions., Conclusions: EPC is associated with decreased LOS and fewer invasive procedures without a change in hospital mortality. Early discussions regarding code status are helpful in decreasing hospital costs and futile interventions. Further investigation is required to standardize palliative care in this population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

With the rising use of Computed Tomography (CT) in diagnostic radiology, there are concerns regarding radiation exposure to sensitive groups, including pregnant patients. Accurately determining the radiation dose to the fetus during CT scans is essential to balance diagnostic efficacy with patient safety. This study assessed the accuracy of using the female uterus as a surrogate for fetal radiation dose during CT imaging. The study used common CT protocols to encompass various scenarios, including primary beam, scatter, and partial exposure. The computational program NCICT was used to calculate radiation doses for an adult female and a fetus phantom. The study highlighted that using the uterus for dose estimation can result in consistent underestimations of the effective dose, particularly when the fetus lies within the primary radiation beam. These discrepancies may influence clinical decisions, affecting care strategies and perceptions of associated risks. In conclusion, while the female uterus can indicate fetal radiation dose if the fetus is outside the primary beam, it is unreliable when the fetus is within the primary beam. More reliable abdomen/pelvic organs were recommended., (© 2024. The Author(s).)

Binaries containing a compact object orbiting a supermassive black hole are thought to be precursors of gravitational wave events, but their identification has been extremely challenging. Here, we report quasi-periodic variability in x-ray absorption, which we interpret as quasi-periodic outflows (QPOuts) from a previously low-luminosity active galactic nucleus after an outburst, likely caused by a stellar tidal disruption. We rule out several models based on observed properties and instead show using general relativistic magnetohydrodynamic simulations that QPOuts, separated by roughly 8.3 days, can be explained with an intermediate-mass black hole secondary on a mildly eccentric orbit at a mean distance of about 100 gravitational radii from the primary. Our work suggests that QPOuts could be a new way to identify intermediate/extreme-mass ratio binary candidates.

The monthly search volumes for drought were extracted from Google® for South Africa using the Keywordsevery-where.com plugin from January 2004 until June 2022. To identify the potential qualitative drivers for such public interest the following data extracted by the plugin were investigated and analysed: the drought-related keywords, the long-tail keywords similar to drought, and the "people also searched for category" from the South African users. The Google Trends monthly score was extracted for South Africa and the Eastern Cape Province, and specific local municipalities/towns/cities in the province. The aim was to assess the relative significance of the drought interest in comparison to public interest in other search terms. The results of the Kruskal-Wallis analyses of variance by ranks showed that there was a statistically significant difference between individual values of the monthly search volumes for drought in South Africa, as a function of time of data extraction (5 percent level of significance; p-value ≤ 4.7 × 10 -14 ). The monthly search volumes increased with time, which is based on the results of the Mann-Kendall test at a 5 percent level of significance (p-value ≤ 0.0092). Analyses of the Google Trends scores indicate that the relative interest in drought in South Africa and the Eastern Cape Province increased with time between January 2004 and June 2022 (the Mann-Kendall test at a 5 percent level of significance; p-value = 0.0011). The population's searches for drought were relatively low when compared to other search terms on Google. Drought adaptation of the South African community could be considered a driver of the Google searches for drought, but it is a marginal topic compared to other topics in Google searches. It might be necessary to increase this significance by investigating the "Google-search patterns for droughts" in the areas of Tshikaro, Mafusini, Cofimvaba, and Nxotsheni in the Eastern Cape Province of South Africa.

Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A Streptococcus (GAS) infections pharyngitis and impetigo. GAS is the only known inciting agent in the pathophysiology of the disease. However, sufficient evidence indicates that the uptake and delivery of primary prevention approaches in RHD-endemic regions are significantly suboptimal. This report presents expert deliberations on priority research and implementation opportunities for primary prevention of ARF/RHD that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. The opportunities identified by the Primary Prevention Working Group encompass epidemiological, laboratory, clinical, implementation and dissemination research domains and are anchored on five pillars including: (A) to gain a better understanding of superficial GAS infection epidemiology to guide programmes and policies; (B) to improve diagnosis of superficial GAS infections in RHD endemic settings; (C) to develop scalable and sustainable models for delivery of primary prevention; (D) to understand potential downstream effects of the scale-up of primary prevention and (E) to develop and conduct economic evaluations of primary prevention strategies in RHD endemic settings. In view of the multisectoral stakeholders in primary prevention strategies, we emphasise the need for community co-design and government engagement, especially in the implementation and dissemination research arena. We present these opportunities as a reference point for research organisations and sponsors who aim to contribute to the increasing momentum towards the global control and prevention of RHD., Competing Interests: Competing interests: ABeaton, AS, CSY and NS received funding support from the National Institutes of Health. ABeaton, AS and MEE received funding support from American Heart Association. ABeaton received funding support from Leducq Foundation, Edwards Lifesciences—Every Heartbeat Matters, The Philips Foundation and Thrasher Pediatric Research Fund. CSY received consultation fees from the WHO. JD received consulting fees from Variation Biotechnology. MEE received funding support from South African Research Council. ABowen receives funding support from the National Health and Medical Research Council of Australia., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) involves continuous antimicrobial prophylaxis among affected individuals and is recognised as a cornerstone of public health programmes that address these conditions. However, several important scientific issues around the secondary prevention paradigm remain unresolved. This report details research priorities for secondary prevention that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. These span basic, translational, clinical and population science research disciplines and are built on four pillars. First, we need a better understanding of RHD epidemiology to guide programmes, policies, and clinical and public health practice. Second, we need better strategies to find and diagnose people affected by ARF and RHD. Third, we urgently need better tools to manage acute RF and slow the progression of RHD. Fourth, new and existing technologies for these conditions need to be better integrated into healthcare systems. We intend for this document to be a reference point for research organisations and research sponsors interested in contributing to the growing scientific community focused on RHD prevention and control., Competing Interests: Competing interests: AB, DW and NS received funding support from the National Institutes of Health. AB received funding support from American Heart Association, Leducq Foundation, Edwards Lifesciences—Every Heartbeat Matters, The Philips Foundation and Thrasher Pediatric Research Fund. MWC received fees as a consultant for Vaxform Incorporated, Serum India Institute and Pfizer Incorporated. MWC is the chief scientific officer and cofounder, with financial interest, in Moleculera Labs, a commercial laboratory for diagnostic testing of autoantibodies against the heart and brain. AR received funding support from the National Health and Medical Research Council. TM received funding support from the Population Health Research Institute (PHRI) & McMaster University, University of Cape Town and University of Witwatersrand., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although entirely preventable, rheumatic heart disease (RHD), a disease of poverty and social disadvantage resulting in high morbidity and mortality, remains an ever-present burden in low-income and middle-income countries (LMICs) and rural, remote, marginalised and disenfranchised populations within high-income countries. In late 2021, the National Heart, Lung, and Blood Institute convened a workshop to explore the current state of science, to identify basic science and clinical research priorities to support RHD eradication efforts worldwide. This was done through the inclusion of multidisciplinary global experts, including cardiovascular and non-cardiovascular specialists as well as health policy and health economics experts, many of whom also represented or closely worked with patient-family organisations and local governments. This report summarises findings from one of the four working groups, the Tertiary Prevention Working Group, that was charged with assessing the management of late complications of RHD, including surgical interventions for patients with RHD. Due to the high prevalence of RHD in LMICs, particular emphasis was made on gaining a better understanding of needs in the field from the perspectives of the patient, community, provider, health system and policy-maker. We outline priorities to support the development, and implementation of accessible, affordable and sustainable interventions in low-resource settings to manage RHD and related complications. These priorities and other interventions need to be adapted to and driven by local contexts and integrated into health systems to best meet the needs of local communities., Competing Interests: Competing interests: JK, SM, MWC and CSY have received funding support from the National Institutes of Health. SM and LJZ received funding support from the South African Medical Research Council. SM received funding support from UNICEF, NIHR and Operation Smile. LJZ also receives support from the National Research Foundation of South Africa (NRFSA), as well as the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, via the African Research Leader Award (MR/S005242/1). CSY received consulting fees from the WHO. MWC received fees as a consultant for Vaxform Incorporated, Serum India Institute and Pfizer Incorporated. MWC is the Chief Scientific Officer and co-founder, with financial interest, in Moleculera Labs, a commercial laboratory for diagnostic testing of autoantibodies against the heart and brain. DV is supported by the Canadian Institutes of Health Research (CIHR) Vanier Canada Graduate Scholarship., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lipopolysaccharide (LPS) produced by the gut during systemic infections and inflammation is thought to contribute to Alzheimer's disease (AD) progression. Since thymosin beta 4 (Tβ4) effectively reduces LPS-induced inflammation in sepsis, we tested its potential to alleviate the impact of LPS in the brain of the APPswePS1dE9 mouse model of AD (APP/PS1) and wildtype (WT) mice. 12.5-month-old male APP/PS1 mice (n = 30) and their WT littermates (n = 29) were tested for baseline food burrowing performance, spatial working memory and exploratory drive in the spontaneous alternation and open-field tests, prior to being challenged with LPS (100ug/kg, i.v.) or its vehicle phosphate buffered saline (PBS). Tβ4 (5 mg/kg, i.v.) or PBS, was administered immediately following and at 2 and 4 h after the PBS or LPS challenge, and then once daily for 6 days (n = 7-8). LPS-induced sickness was assessed though monitoring of changes in body weight and behaviour over a 7-day period. Brains were collected for the determination of amyloid plaque load and reactive gliosis in the hippocampus and cortex. Treatment with Tβ4 alleviated sickness symptoms to a greater extent in APP/PS1 than in WT mice by limiting LPS-induced weight loss and inhibition of food burrowing behaviour. It prevented LPS-induced amyloid burden in APP/PS1 mice but increased astrocytic and microglial proliferation in the hippocampus of LPS-treated WT mice. These data show that Tβ4 can alleviate the adverse effects of systemic LPS in the brain by preventing exacerbation of amyloid deposition in AD mice and by inducing reactive microgliosis in aging WT mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Childhood cancer survivors (CCS) are at increased risk of developing skin cancer. Engaging in sun-protective behaviors may ameliorate that risk, but prior work shows that survivors engage in suboptimal levels of sun-protective behaviors. Guided by the Health Belief Model (HBM), this study evaluated factors associated with sun-protective behavior among CCS., Methods: This is a secondary analysis of a survey study of 94 adult survivors of childhood cancer recruited from a long-term follow-up clinic. Participants reported their sun protection habits, skin type/sensitivity, barriers to sun protection, and perceived severity and susceptibility of getting skin cancer. Descriptive statistics were used to describe the prevalence of sun protection behaviors and hierarchical linear regression was used to evaluate predictors of sun protection behavior following the HBM., Results: On average, CCS engaged in moderate levels of sun-protective behaviors ( M =2.53; SD=0.59). Hierarchical linear regression indicated that fair skin type ( P =0.02) and higher perceived susceptibility relative to noncancer survivors ( P =0.02) were associated with increased sun protection behaviors. Perceived barriers to sun protection were marginally significant ( P =0.09), whereas other constructs from the HBM did not contribute significantly to the model., Conclusions: Although CCS are at increased risk of developing skin cancer, they engage in suboptimal levels of sun protection behaviors. Findings suggest that interventions to educate survivors about their unique risk of skin cancer and effective prevention behaviors are needed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Childhood cancer survivors require lifelong risk-based follow-up care. It should be noted that less than one-third of adult survivors of childhood cancer report any survivor-focused care, and fewer than 1 in 5 obtain risk-based follow-up care. It is thought that this may be due to inadequate transition readiness, including low levels of knowledge, skills, motivation, and resources to make the transition to independent self-management of follow-up care. Interventions that focus specifically on improving the transition from parent-managed to self-managed care are needed. Theory and prior research suggest that targeting self-management skills and using peer mentoring may be innovative strategies to improve transition readiness., Objective: This study aims to identify the content of a self-management intervention to improve transition readiness among adolescent and young adult (AYA) survivors., Methods: Intervention development occurred in 3 stages: formative research with AYA survivors to identify barriers and facilitators to obtaining risk-based survivorship care, content development using feedback from multiple stakeholders (AYA survivors, parents, and providers), and content refinement (usability testing) of the initial proposed educational modules for the program. Content analysis, guided by the social-ecological model of AYA readiness for transition, was used to identify themes and develop and refine the content for the intervention., Results: A total of 19 AYA survivors participated in the formative research stage, and 10 AYA survivors, parents, and health care providers participated in the content development and refinement stages. The major barrier and facilitator themes identified included knowledge of cancer history and risks; relationships with health care providers; relationships with family members involved in care; emotions about health, follow-up care, and transfer of care; and lifestyle behaviors and life transitions. These themes were translated into 5 self-management modules: understanding treatment history and the survivorship care plan, managing health care logistics and insurance, communicating with health care providers and family members involved in care, dealing with emotions, and staying healthy in the context of life transitions. Feedback from the key stakeholders indicated that the content was relevant but should include participative elements (videos and tailored feedback) to make the intervention more engaging. The AYA survivors were receptive to the idea of working with a peer mentor and expressed a preference for using SMS text messaging, telephone calls, or videoconference to communicate with their mentor., Conclusions: Incorporating AYA survivors, parents, and providers in the design was essential to developing the content of a self-management and peer-mentoring intervention. AYA survivors confirmed the important targets for the intervention and facilitated design decisions in line with our target users' preferences. The next step will be to conduct a single-arm trial to determine the feasibility and acceptability of the proposed intervention among AYA survivors of childhood cancer., (©Adrienne S Viola, Kristine Levonyan-Radloff, Margaret Masterson, Sharon L Manne, Shawna V Hudson, Katie A Devine. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.08.2022.)

The judicious use of antimicrobials on farms is necessary to mitigate the development of antimicrobial-resistant pathogens that compromise human and animal health. On livestock farms, veterinarians prescribe and dispense antimicrobials, but producers use rapid judgements of disease severity to make routine decisions on the initiation of empirical antimicrobial therapy. Therefore, the knowledge and skills required to accurately diagnose treatable bacterial infections is necessary for optimal antimicrobial stewardship. Veal calves often undergo stressors and environmental exposures that increase calves' risk of bacterial infections, and antimicrobials are sometimes necessary to ensure their health. The objective of this trial was to measure the impact of antimicrobial stewardship training on calf producers' knowledge of antimicrobial stewardship, accuracy of identifying calves for treatment, and quantified antimicrobial use. Eight farms were evenly allocated into either intervention or control groups. Training resulted in both higher scores on assessments and higher sensitivity for detecting cases that required antimicrobial therapy relative to a veterinarian. Importantly, there was a 50% reduction in the antimicrobial dosing rate among intervention farms relative to control farms. Antimicrobial stewardship training among calf producers was effective at changing producers' behaviors and reducing antimicrobial use.

Background: Lymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases., Methods: We examined the genomic landscape of a patient cohort of LMs ( n = 30 cases) that underwent comprehensive genomic profiling using a large-panel next-generation sequencing assay. Immunohistochemical analyses were completed in parallel., Results: These LMs had low mutational burden with hotspot PIK3CA mutations ( n = 20) and NRAS ( n = 5) mutations being most frequent, and mutually exclusive. All LM cases with Kaposi sarcoma-like (kaposiform) histology had NRAS mutations. One index patient presented with subacute abdominal pain and was diagnosed with a large retroperitoneal LM harboring a somatic PIK3CA gain-of-function mutation (H1047R). The patient achieved a rapid and durable radiologic complete response, as defined in RECIST1.1, to the PI3Kα inhibitor alpelisib within the context of a personalized N -of-1 clinical trial (NCT03941782). In translational correlative studies, canonical PI3Kα pathway activation was confirmed by immunohistochemistry and human LM-derived lymphatic endothelial cells carrying an allele with an activating mutation at the same locus were sensitive to alpelisib treatment in vitro, which was demonstrated by a concentration-dependent drop in measurable impedance, an assessment of cell status., Conclusions: Our findings establish that LM patients with conventional or kaposiform histology have distinct, yet targetable, driver mutations., Funding: R.P. and W.A. are supported by awards from the Levy-Longenbaugh Fund. S.G. is supported by awards from the Hugs for Brady Foundation. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of Arizona Cancer Center (CA023074), the University of New Mexico Comprehensive Cancer Center (CA118100), and the Rutgers Cancer Institute of New Jersey (CA072720). B.K.M. was supported by National Science Foundation via Graduate Research Fellowship DGE-1143953., Clinical Trial Number: NCT03941782., Competing Interests: MS reports personal fees from Illumina, BMS, and Qiagen (outside of the submitted work). The author has no other competing interests to declare, JT, ES is an employee of Foundation Medicine, Inc, a wholly owned subsidiary of Roche, and owns equity in Roche. The author has no other competing interests to declare, MM, PB, IR, CT, AD, TS, TB, RG, JB, SN, GR No competing interests declared, BM is an employee of Foundation Medicine, Inc, a wholly owned subsidiary of Roche, and owns equity in Roche, RG reports research funding/grant support for clinical trials (to his institution) from Regeneron, BMS, Merck/EMD Serano, Amgen, Roche/Genentech, Philogen; consulting/advisory board fees from Regeneron; and speaker fees for Deciphera (all outside of the submitted work). These arrangements are managed in accordance with the established institutional conflict of interest policies of Rutgers, The State University of New Jersey. The author has no other competing interests to declare, RP, WA Reviewing editor, eLife, SG has consulting agreements with Merck, Roche, Novartis, Foundation Medicine, EQRX, Foghorn Therapeutics, Silagene, and KayoThera and owns equity in Silagene; his spouse is an employee of Merck and owns equity in Merck (all outside of the submitted work). These arrangements are managed in accordance with the established institutional conflict of interest policies of Rutgers, The State University of New Jersey. The author has no other competing interests to declare, (© 2022, Shaheen, Tse et al.)

Steroid hormones control development and homeostasis in a wide variety of animals by interacting with intracellular nuclear receptors. Recent discoveries in the fruit fly Drosophila melanogaster revealed that insect steroid hormones or ecdysteroids are incorporated into cells through a membrane transporter named Ecdysone Importer (EcI), which may become a novel target for manipulating steroid hormone signaling in insects. In this study, we established an assay system that can rapidly assess EcI-mediated ecdysteroid entry into cultured cells. Using NanoLuc Binary Technology (NanoBiT), we first developed an assay to detect ligand-dependent heterodimerization of the ecdysone receptor (EcR) and retinoid X receptor (RXR) in human embryonic kidney (HEK) 293T cells. We also developed HEK293 cells that stably express EcI. By combining these tools, we can monitor ecdysteroid entry into the cells in real time, making it a reliable system to assess EcI-mediated steroid hormone incorporation into animal cells., Competing Interests: RB, SH-Y, and NY have a patent (U.S. Patent No. 10,228,380) relevant to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Masterson, Bittar, Chu, Yamanaka and Haga-Yamanaka.)

There is growing interest in understanding antibody (Ab) function beyond neutralization. The non-structural protein 1 (NS1) of Zika virus (ZIKV) is an attractive candidate for an effective vaccine as Abs against NS1, unlike the envelope or premembrane, do not carry the risk of mediating antibody-dependent enhancement. Our aim was to evaluate whether ZIKV NS1 Abs elicited following natural infection in humans can mediate antibody-dependent cellular cytotoxicity (ADCC). We evaluated the isotype specificity of ZIKV-specific Abs in immune sera and supernatants from stimulated immune PBMC and found that Abs against ZIKV NS1 and virus-like particles were predominantly of the IgG1 isotype. Using a recently developed FluoroSpot assay, we found robust frequencies of NS1-specific Ab-secreting cells in PBMC of individuals who were naturally infected with ZIKV. We developed assays to measure both natural killer cell activation by flow cytometry and target cell lysis of ZIKV NS1-expressing cells using an image cytometry assay in the presence of ZIKV NS1 Abs. Our data indicate efficient opsonization of ZIKV NS1-expressing CEM-NK R cell lines using ZIKV-immune but not ZIKV-naïve sera, a prerequisite of ADCC. Furthermore, sera from immune donors were able to induce both NK cell degranulation and lysis of ZIKV NS1 CEM-NK R cells in vitro. Our data suggest that ADCC is a possible mechanism for ZIKV NS1 Abs to eliminate virally infected target cells., (© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)

Background: This study evaluated the feasibility of a technology-enhanced group-based fitness intervention for adolescent and young adult (AYA) survivors of childhood cancer., Procedure: AYA survivors ages 13-25 years were randomized to the intervention (eight in-person group sessions with mobile app and FitBit followed by 4 weeks of app and FitBit only) or waitlist control. Assessments were at 0, 2, 3, 6, and 9 months. Feasibility was evaluated by enrollment, retention, attendance, app engagement, and satisfaction. Secondary outcomes included physical activity, muscular strength/endurance, cardiorespiratory fitness, health-related quality of life, and fatigue., Results: A total of 354 survivors were mailed participation letters; 68 (19%) were screened, of which 56 were eligible and 49 enrolled (88% of those screened eligible, 14% of total potentially eligible). Forty-nine survivors (M age  = 18.5 years, 49% female) completed baseline assessments and were randomized (25 intervention, 24 waitlist). Thirty-seven (76%) completed the postintervention assessment and 32 (65%) completed the final assessment. On average, participants attended 5.7 of eight sessions (range 1-8). Overall intervention satisfaction was high (M = 4.3, SD = 0.58 on 1-5 scale). Satisfaction with the companion app was moderately high (M = 3.4, SD = 0.97). The intervention group demonstrated significantly greater improvement in lower body muscle strength compared to the waitlist postintervention, and small but not statistically significant changes in other secondary measures., Conclusions: A group-based intervention with a mobile app and fitness tracker was acceptable but has limited reach due to geographical barriers and competing demands experienced by AYA survivors., (© 2020 Wiley Periodicals LLC.)

Background: Nausea is one of the most commonly reported side effects in patients receiving chemotherapy. Patients who experience nausea during chemotherapy may also experience depression, metabolic imbalances, dehydration, decreased ability to function, and treatment delays, which can ultimately affect outcomes., Objectives: This study aimed to determine the efficacy of a cool damp washcloth with peppermint essential oil versus a cool damp washcloth alone on the self-reported intensity of nausea in patients receiving chemotherapy in the outpatient ambulatory setting., Methods: 79 adult patients receiving chemotherapy were recruited from an outpatient ambulatory infusion center in the southeastern United States. Patients were separated into two groups (no scent and peppermint) and asked to rate the intensity of their chemotherapy-induced nausea at pre- and postintervention using the Baxter Retching Faces pictorial scale., Findings: The results demonstrated that the use of peppermint oil was effective in decreasing the intensity of nausea experienced by patients compared to a cool washcloth alone.

Objectives: A goal of family-focused therapies in oncology is to help families communicate effectively about illness and its management. Yet there has been no examination of whether and how conjoint sessions are conducive to this process. In this study, we (a) described the extent of cancer-specific communication during family sessions at the end of life; (b) identified characteristics associated with SC; and (c) determined the association between SC and longer-term family bereavement outcomes., Methods: Data were collected as part of a randomized controlled trial of Family Focused Grief Therapy (FFGT) for advanced cancer patients and their families. Demographics, depressive symptoms, and family functioning were assessed at baseline. Cancer-specific communication, perceived responsiveness to communication, and therapeutic alliances were reported after each session. At 13-month bereavement, surviving families were assessed for symptoms of depression and prolonged grief disorder (PGD)., Results: Participants were 257 advanced cancer patients and family members receiving FFGT at the end of life. On average, participants perceived significantly more cancer-related communication in session (SC) than at baseline. Both therapist-family and within-family alliances were associated with SC, especially for those with more severe depressive symptoms at baseline. Long-term outcomes were moderated by perceived responsiveness to in-session communication: for those who perceived high responsiveness, SC was associated with fewer depressive and PGD symptoms in bereavement., Conclusions: Conjoint family sessions can effectively increase communication about cancer at the end of life. Clinicians should consider key contextual factors in their effort to facilitate this process: perceived responsiveness, family role, alliances with therapist, and within-family., (© 2019 John Wiley & Sons, Ltd.)

Purpose: The new lower eye lens dose limit is of relevance in interventional radiology, where higher dose procedures result in increased scattered radiation to staff. The eye lens dose may be monitored using the directional dose equivalent at 3 mm depth, H p (3), or through H p (10) or H p (0.07) measurements and using conversion factors. However, there are a considerable range of factors which contribute to measurement uncertainties, one of which is the incident photon energy. This study investigated the energy spectra of scattered radiation in interventional radiology, and the dosimetry accuracy of dosimeter types, evaluating their energy dependence., Methods: Scatter X-ray energy spectra were recorded under varied conditions in a fluoroscopy imaging suite. Dosimetry accuracy of eye dosimeters, including TLDs (100 s, 100Hs), Landauer H p (3), John Caunt ED3 and Electronic Personal dosimeters (EPDs) were compared to air kerma measurements across a range of tube voltages., Results: The variation of energy spectra with changing phantom thickness, spectrometer angulation and filtration are presented. The 100 and 100H TLDs, and EPDs showed a consistent air kerma response (within 10%) with changes in energy. The real-time silicon diode detectors showed a variable over response of between 10 and 25% across the energies investigated while Landauers dedicated H p (3) eye dosimeters showed considerable variation between dosimeters for similar conditions, a 17% variation at 50 kV p ., Conclusion: The work aimed to validate the scattered energy spectra typically encountered in interventional radiology and to further determine the accuracy of eye dosimeters in relation to energy response variations., (Copyright © 2019 Associazione Italiana di Fisica Medica. All rights reserved.)

Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with glucanosyltransferase and β-1,3 endoglucanase activity in other fungi. Pneumocystis murina, Pneumocystis carinii, and Pneumocystis jirovecii bgl2 complementary DNA sequences encode proteins of 437, 447, and 408 amino acids, respectively. Recombinant P. murina Bgl2 expressed in COS-1 cells demonstrated β-glucanase activity, as shown by degradation of the cell wall of Pneumocystis cysts. It also cleaved reduced laminaripentaose and transferred oligosaccharides, resulting in polymers of 6 and 7 glucan residues, demonstrating glucanosyltransferase activity. Surprisingly, confocal immunofluorescence analysis of P. murina-infected mouse lung sections using an antibody against recombinant Bgl2 showed that the native protein is localized primarily to the trophic form of Pneumocystis in both untreated mice and mice treated with caspofungin, an antifungal drug that inhibits β-1,3-glucan synthase. Thus, like other fungi, Bgl2 of Pneumocystis has both endoglucanase and glucanosyltransferase activities. Given that it is expressed primarily in trophic forms, further studies are needed to better understand its role in the biology of Pneumocystis., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Objective: To determine the preliminary feasibility, acceptability, and effects of Meaning-Centered Grief Therapy (MCGT) for parents who lost a child to cancer., Method: Parents who lost a child to cancer and who were between six months and six years after loss and reporting elevated levels of prolonged grief were enrolled in open trials of MCGT, a manualized, one-on-one cognitive-behavioral-existential intervention that used psychoeducation, experiential exercises, and structured discussion to explore themes related to meaning, identity, purpose, and legacy. Parents completed 16 weekly sessions, 60-90 minutes in length, either in person or through videoconferencing. Parents were administered measures of prolonged grief disorder symptoms, meaning in life, and other assessments of psychological adjustment preintervention, mid-intervention, postintervention, and at three months postintervention. Descriptive data from both the in-person and videoconferencing open trial were pooled.ResultEight of 11 (72%) enrolled parents started the MCGT intervention, and six of eight (75%) participants completed all 16 sessions. Participants provided positive feedback about MCGT. Results showed postintervention longitudinal improvements in prolonged grief (d = 1.70), sense of meaning (d = 2.11), depression (d = 0.84), hopelessness (d = 1.01), continuing bonds with their child (d = 1.26), posttraumatic growth (ds = 0.29-1.33), positive affect (d = 0.99), and various health-related quality of life domains (d = 0.46-0.71). Most treatment gains were either maintained or increased at the three-month follow-up assessment.Significance of resultsOverall, preliminary data suggest that this 16-session, manualized cognitive-behavioral-existential intervention is feasible, acceptable, and associated with transdiagnostic improvements in psychological functioning among parents who have lost a child to cancer. Future research should examine MCGT with a larger sample in a randomized controlled trial.

Background: European trials using procalcitonin (PCT)-guided antibiotic therapy for patients with lower respiratory tract infections (LRTIs) have demonstrated significant reductions in antibiotic use without increasing adverse outcomes. Few studies have examined PCT for LRTIs in the United States., Methods: In this study, we evaluated whether a PCT algorithm would reduce antibiotic exposure in patients with LRTI in a US hospital. We conducted a controlled pre-post trial comparing an intervention group of PCT-guided antibiotic therapy to a control group of usual care. Consecutive patients admitted to medicine services and receiving antibiotics for LRTI were enrolled in the intervention. Providers were encouraged to discontinue antibiotics according to a PCT algorithm. Control patients were similar patients admitted before the intervention., Results: The primary endpoint was median antibiotic duration. Overall adverse outcomes at 30 days comprised death, transfer to an intensive care unit, antibiotic side effects, Clostridium difficile infection, disease-specific complications, and post-discharge antibiotic prescription for LRTI. One hundred seventy-four intervention patients and 200 controls were enrolled. Providers complied with the PCT algorithm in 75% of encounters. Procalcitonin-guided therapy reduced median antibiotic duration for pneumonia from 7 days to 6 ( P = .045) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) from 4 days to 3 ( P = .01). There was no difference in the rate of adverse outcomes in the PCT and control groups., Conclusions: A PCT-guided algorithm safely reduced the duration of antibiotics for treating LRTI. Utilization of a PCT algorithm may aid antibiotic stewardship efforts.This clinical trial was a single-center, controlled, pre-post study of PCT-guided antibiotic therapy for LRTI. The intervention (incorporation of PCT-guided algorithms) started on April 1, 2017: the preintervention (control group) comprised patients admitted from November 1, 2016 to April 16, 2017, and the postintervention group comprised patients admitted from April 17, 2017 to November 29, 2017 (Supplementary Figure 1). The study comprised patients admitted to the internal medicine services to a medical ward, the Medical Intensive Care Unit (MICU), the Cardiac Intensive Care Unit (CICU), or the Progressive Care Unit (PCU) "step down unit". The registration data for the trails are in the ClinicalTrials.gov database, number NCT0310910.

Background: Patients with advanced cancer have high rates of psychological distress, including depression, anxiety, and spiritual despair. This study examined the effectiveness of individual meaning-centered psychotherapy (IMCP) in comparison with supportive psychotherapy (SP) and enhanced usual care (EUC) in improving spiritual well-being and quality of life and reducing psychological distress in patients with advanced cancer., Methods: Patients (n = 321) were randomly assigned to IMCP (n = 109), SP (n = 108), or EUC (n = 104). Assessments were conducted at 4 time points: before intervention, midtreatment (4 weeks), 8 weeks after treatment, and 16 weeks after treatment., Results: Significant treatment effects (small to medium in magnitude) were observed for IMCP, in comparison with EUC, for 5 of 7 outcome variables (quality of life, sense of meaning, spiritual well-being, anxiety, and desire for hastened death), with Cohen's d ranging from 0.1 to 0.34; no significant improvement was observed for patients receiving SP (d < 0.15 and P > .05 for all variables). The effect of IMCP was significantly greater than the effect of SP for quality of life and sense of meaning (d = 0.19) but not for the remaining study variables., Conclusions: This study provides further support for the efficacy of IMCP as a treatment for psychological and existential/spiritual distress in patients with advanced cancer. Significant treatment effects (small to moderate effect sizes) were observed in comparison with usual care, and somewhat more modest differences in improvement (small effect sizes) were observed in comparison with SP. Thus, the benefits of meaning-centered psychotherapy appear to be unique to the intervention and highlight the importance of addressing existential issues with patients approaching the end of life. Cancer 2018. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Introduction: Recovery of erections after radical prostatectomy (RP) is assumed to lead to recovery in sexual satisfaction. Although data suggest a relationship between sexual function and sexual satisfaction, it is unclear whether presurgical levels of sexual satisfaction are attained for men who "recover" erections post-RP., Aim: The goal of this analysis is to determine whether the recovery of erectile function restores presurgical levels of sexual satisfaction., Methods: We assessed 229 men pre-RP and 24-months post-RP. At both time points, participants completed the Erectile Function Domain (EFD) and the Intercourse Satisfaction Domain (ISD) of the International Index of Erectile Function (IIEF). Erectile function recovery at 24 months was defined as (1) (EFD≥24) or (2) EFD back to baseline (BTB). One hundred sixty-six men with penetration hardness erections (PHEs) at baseline (EFD >24) were included in the analyses. Repeated measure t-tests were used to compare changes in ISD scores and effect size (Cohen's d) was calculated to determine the clinical significance of these changes. Multivariable analyses (MVA) were used to test the relationship between EFD and ISD., Results: The mean age of men was 58 (SD = 7) years. The mean EFD score at baseline was 29 (SD = 2), which declined significantly to 20 (SD = 10) at 24 months. ISD also decreased significantly between baseline and 24 months (12 to 8.3, P < .001, d = 0.87), even among men with PHEs at 24 months (12.3 to 11.3, P < .001, d = 0.50) and men who achieved BTB erections at 24 months (12.4 to 11.7, P = .02, d = 0.35). For men with PHEs at 24 months, MVAs identified baseline ISD (beta = 0.46) and 24-month EFD (beta = 0.23) as the only significant predictors of 24-month ISD. However, among men who achieved BTB erections at 24 months, baseline ISD (beta = 0.49) was the only significant predictor of 24-month ISD., Clinical Implications: These findings underscore the importance of the integration of psychological support and medical care to best meet the needs of patients. Furthermore, these results can be used to facilitate pre-RP communication and counseling with patients to improve understanding and manage post-RP expectations., Strengths & Limitations: The study methodology, specifically the use of BTB as a means of defining erectile function and the longitudinal, prospective study design are relative strengths. Despite the longitudinal design, the study did not include a control group of healthy, age-matched men., Conclusion: Results highlight the enduring impact of sexual dysfunction, namely erectile dysfunction, on intercourse satisfaction following RP and suggest that restoration of function in and of itself does not ensure the restoration of satisfaction. Terrier JE, Masterson M, Mulhall JP, et al. Decrease in intercourse satisfaction in men who recover erections after radical prostatectomy. J Sex Med 2018;15:1133-1139., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The inherent disease susceptibility of veal calves results in frequent antimicrobial use. Improvements in antimicrobial stewardship necessitate alternative therapies to improve calf health and growth, while reducing the need for antimicrobials important to human health. This study investigated the effect of 2 alternative therapies, lactoferrin (an iron-binding protein found in colostrum) and cinnamaldehyde (an essential oil of the cinnamon plant) on growth, disease incidence, and mortality risk in special-fed veal calves. On the day of arrival to the growing facility (3 to 7 d of age), calves (n = 80 per treatment) were randomized to 1 of 3 treatments: (1) control (no supplement), (2) lactoferrin (1 g/d in milk replacer for 7 d), or (3) cinnamaldehyde (1 g/d in milk replacer for 21 d). Body weight was measured on the day of arrival (d 0), 21, and 42 d postarrival. Health assessments were performed twice weekly through 21 d, and mortality records were obtained through 6 wk postarrival. A repeated-measures ANOVA was used to compare growth between treatment groups, and a Poisson regression model (PROC GENMOD, SAS v. 9.4, SAS Institute Inc., Cary, NC) was used to test differences between groups in the incidence of diarrhea (fecal score ≥2 with and without depression and temperature) and disease through 3 wk postarrival. Body weight and average daily gain were similar between treatments. Neither lactoferrin nor cinnamaldehyde had an effect on diarrhea incidence. However, the risk of navel inflammation was significantly lower for calves that received cinnamaldehyde compared with calves in the control group. Mortality through 6 wk postarrival was low, with 4, 1, and 0 deaths from the control, lactoferrin, and cinnamaldehyde treatment groups, respectively. Additional research is needed to investigate various doses of these alternative therapies on calf health and growth, in addition to different routes of administration., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Transmission of antimicrobial resistance (AMR) from animal production systems to humans through the food supply is a public health concern. Currently, little is known about the prevalence of AMR among veal calves in the United States. Therefore, the objective of this prospective cohort study was to estimate the prevalence of AMR and multidrug resistance (MDR) among Escherichia coli within a vertically integrated production system. In addition, this study aimed to identify genes associated with phenotypic resistance to third- and fourth-generation cephalosporins (3GC and 4GC). Calves from four veal cohorts were randomly sampled resulting in a total of 166 farm fecal samples, 159 harvest fecal swabs, 164 preevisceration swabs, and 122 final carcass swabs. The prevalence of MDR among random-pick E. coli isolates recovered from the respective samples was 97% (161/166), 35% (55/159), 61% (51/84), and 24% (5/21). A selective isolation protocol found cefotaxime (a 3GC)-resistant isolates in 91% (127/140) of farm fecal samples, 34% (55/164) of preevisceration swabs, and 19% (23/122) of final carcass swabs tested. Isolates resistant to cefepime, a 4GC, were found among 24% (33/140), 6.7% (11/164), and 0.8% (1/122) of the same, respective samples. Isolates resistant to ciprofloxacin, a fluoroquinolone, were recovered from 75% (73/98) of farm fecal samples, 23% (38/164) of preevisceration swabs, and 6.6% (8/122) of final carcass swabs. The bla CMY-2 and bla CTX-M resistance genes were found in 89% (93/105) and 100% (42/42) of tested subsets of 3GC- and 4GC-resistant isolates, respectively. Pulsed-field gel electrophoresis (PFGE) analysis conducted on 3GC- and fluoroquinolone-resistant isolates showed three indistinguishable PFGE patterns from cefotaxime-resistant isolates recovered at farm and from two preevisceration carcass swabs. Although the prevalence of resistance declined between initial farm fecal samples and final carcass swabs, resistant bacteria recovered from carcasses illustrate the potential transmission of AMR to the human food supply.

Veal calves are at high risk for disease and mortality in early life. Calves face a number of stressors before arriving at the grower, including long transport times, which may contribute to poor health. Our objectives were to 1) estimate the prevalence of poor health outcomes in veal calves on arrival at growers in Ohio; 2) determine risk factors for health outcomes on arrival, including BW and auction site (spread across 5 states in the Northeastern United States); and 3) determine if health outcomes on arrival predict early mortality. A physical examination was conducted on approximately 30 calves (mean of 45.9 kg [SD 3.0]) from 12 cohorts ( = 383 calves). Exams included a blood sample to determine packed cell volume (an estimate of dehydration using a cutoff > 46%) and total protein (an estimate failure of passive transfer using a cutoff < 5.5 g/dL and 6.0 g/dL to account for dehydration). Diarrhea, respiratory disease, depression, navel inflammation, and a skin tent test (a second indicator of dehydration) were also recorded. Mortality within 4 wk of age was collected from farm records. Descriptive statistics were used to describe the prevalence of calves with poor health outcomes on arrival. Generalized linear mixed models were used to identify risk factors for poor health on arrival and assess if poor health increased the incidence risk of mortality. Upon arrival, 6% (95% confidence interval 4.4 to 7.6%) of calves had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 5.5 g/dL, and 22.5% (18.1 to 26.8%) had failure of passive transfer using a cut-off of 6.0%; 14% (9.1 to 18.8%) had diarrhea, 0.5% (0 to 1.3%) had respiratory disease, 14% (8.5 to 19.3%) were depressed, and 27% (22.7 to 30.7%) had inflamed navels. In addition, 35.1% (23.5 to 46.6%) of calves were dehydrated using a skin tent test, but only 1.3% (0.0 to 2.9%) were dehydrated based on the packed cell volume threshold. Auction site was associated with depression on arrival ( = 0.008) and tended to be associated with skin tent on arrival ( = 0.08). None of the health variables were predictors of early mortality; however, mortality was generally low for all cohorts (4.3%; range 1.7 to 6.8%). These results estimate the prevalence of dehydration, diarrhea, navel inflammation, and depression in veal calves on arrival at growers and demonstrate that some health outcomes are dependent on auction site. We conclude that there are many opportunities to intervene to improve their health and welfare before the calves arrive at the grower.

Context and Objectives: Screening and baseline data on 170 American families (620 individuals), selected by screening from a palliative care population for inclusion in a randomized controlled trial of family-focused grief therapy, were examined to determine whether family dysfunction conferred higher levels of psychosocial morbidity. We hypothesized that greater family dysfunction would, indeed, be associated with poorer psychosocial outcomes among palliative care patients and their family members., Methods: Screened families were classified according to their functioning on the Family Relationships Index (FRI) and consented families completed baseline assessments. Mixed-effects modeling with post hoc tests compared individuals' baseline psychosocial outcomes (psychological distress, social functioning, and family functioning on a different measure) according to the classification of their family on the FRI. Covariates were included in all models as appropriate., Results: For those who completed baseline measures, 191 (30.0%) individuals were in low-communicating families, 313 (50.5%) in uninvolved families, and 116 (18.7%) in conflictual families. Family class was significantly associated (at ps ≤ 0.05) with increased psychological distress (Beck Depression Inventory and Brief Symptom Inventory) and poorer social adjustment (Social Adjustment Scale) for individual family members. The family assessment device supported the concurrent accuracy of the FRI., Conclusion: As predicted, significantly greater levels of individual psychosocial morbidity were present in American families whose functioning as a group was poorer. Support was generated for a clinical approach that screens families to identify those at high risk. Overall, these baseline data point to the importance of a family-centered model of care., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: To establish preliminary evidence for the feasibility, acceptability, and utility of an abbreviated version of Meaning-Centered Psychotherapy tailored to the needs of palliative care patients in the final weeks or months of life., Background: Surprisingly, few mental health interventions have specifically targeted the psychological needs of palliative care patients, when physical comfort seems to take precedence over mental health and emotional needs. Yet the need for mental health services targeting these patients is clear, as one in three palliative care patients experience clinically significant depression and an equal proportion experience clinically significant anxiety., Design: This pilot study used an open-label design to assess the feasibility, acceptability, and perceived utility of Meaning-Centered Psychotherapy-palliative care, a brief intervention that focuses on enhancing meaning at the end of life., Setting/participants: A total of 12 patients admitted to a palliative care hospital for supportive care consented to participate in the study., Results: Of the 11 patients that began treatment (one patient died before the first session), 8 completed the three-session intervention. Patients expressed positive feedback about the structure, focus, and length of the intervention, but varied in precisely which elements they found most helpful., Conclusion: An abbreviated version of Meaning-Centered Psychotherapy tailored to the needs of palliative care patients (Meaning-Centered Psychotherapy-palliative care) appears to be feasible, acceptable, and has the potential to help patients better cope with the challenges inherent in confronting death and dying. Further research, with larger and more representative samples, is needed in order to clarify the strengths and weaknesses of this approach.

The Cancer Institute of New Jersey Acute Lymphoblastic Leukemia trial (CINJALL) employed a post-induction regimen centered on intensive oral antimetabolite therapy, with no intravenous methotrexate (MTX). Fifty-eight patients enrolled between 2001 and 2005. A high rate of induction death (n = 3) or induction failure (n = 1) was observed. Among those who entered remission, five-year DFS is 80 ± 8.9% for those at standard risk of relapse and 76 ± 7.8% for high-risk patients, with median follow up over six years. The estimated cumulative incidence of testicular relapse among boys was elevated (13 ± 7.2%) compared to the rate observed on contemporary protocols. We conclude that post-induction therapy using intensive oral antimetabolites for children with acute lymphoblastic leukemia (ALL) can result in overall long-term DFS comparable to that observed among children treated with regimens including intravenous MTX. However, an increased risk of late extramedullary relapse among boys was observed, supporting the prevailing opinion that high-dose MTX improves outcome for children with ALL.

The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination (SSE) and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of SSEs did not differ based on treatment history. These findings highlight the need to promote skin cancer surveillance as an important aspect of CCS survivorship care., (© 2015 Wiley Periodicals, Inc.)

This case describes a young adult male patient diagnosed and treated for a primitive neuroectodermal tumour (PNET) at 3 years of age. Chemotherapy and radiation therapy used following surgical treatment of this tumour have known neurotoxic complications, some of which have delayed onset. In this case, the patient exhibited sudden onset, persistent bilateral and deep ear pain that was consistent with a neuropathy of the glossopharyngeal nerve occurring 17 years after the completion of therapy for PNET. Treatment with pregabalin was successful with near-complete resolution of the complaint. The diagnostic certainty in this case is discussed in relation to the current diagnostic criteria for neuropathic pain., (© 2015 John Wiley & Sons Ltd.)

Context: Poor family functioning affects psychosocial adjustment and the occurrence of morbidity following bereavement in the context of a family's coping with advanced cancer. Family functioning typologies assist with targeted family-centered assessment and intervention to offset these complications in the palliative care setting., Objectives: Our objective was to identify the number and nature of potential types in an American palliative care patient sample., Methods: Data from patients with advanced cancer (N = 1809) screened for eligibility for a larger randomized clinical trial were used. Cluster analyses determined whether patients could be classified into clinically meaningful and coherent groups, based on similarities in their perceptions of family functioning across the cohesiveness, expressiveness, and conflict resolution subscales of the Family Relations Index., Results: Patients' reports of perceived family functioning yielded a model containing five meaningful family types., Conclusion: Cohesiveness, expressiveness, and conflict resolution appear to be useful dimensions by which to classify patient perceptions of family functioning. "At risk" American families may include those we have called hostile, low-communicating, and less-involved. Such families may benefit from adjuvant family-centered psychosocial services, such as family therapy., Competing Interests: The authors have no disclosures or conflicts of interest to report., (Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Ovarian torsion (OT) is one of the most common gynecologic surgical emergencies. All age groups can be affected, but ovarian stimulation, as found during early pregnancy or infertility treatment, is a major risk factor., Objective: Diagnosing OT in early pregnancy can be challenging. Patients frequently present with abdominal pain and non-specific symptoms. Missed diagnosis of OT could lead not only to ovarian necrosis and sepsis, but also threaten the pregnancy. The objective of this article is to present a case of OT in early pregnancy and to review its epidemiology, diagnosis, and treatment., Case Report: A 30-year-old woman at 10 weeks gestational age presented to the Emergency Department (ED) with 2 h duration of abdominal pain, nausea, and vomiting. The patient was not on ovarian stimulation treatments. A bedside ED ultrasound showed an enlarged edematous right ovary with a large cyst, but without flow on color Doppler. Immediate obstetric consultation was initiated. Eventual radiology ultrasound showed decreased but present flow in the right ovary. The patient underwent emergent laparoscopic surgery, during which the necrotic right ovary was removed. She was placed on progesterone therapy upon hospital discharge and eventually delivered a healthy term infant., Conclusions: Ovarian torsion in pregnancy is increasing in frequency due to the growing prevalence of ovarian stimulation treatment. Although diagnostic ultrasound is a frequently used imaging tool in patients with suspected OT, the mere presence of blood flow on Doppler ultrasonography of the adnexa has a poor negative predictive value. A high clinical suspicion and early laparoscopic management correlate with favorable maternal and fetal outcomes., (Published by Elsevier Inc.)

Purpose: This study investigated the effects of a 10-week hippotherapy program on trunk, pelvis, and hip joint positioning during the stance phase of gait., Methods: Eleven children (6 boys and 5 girls; 7.9 ± 2.7 years) with neurological disorders and impaired ambulation participated. Joint range of motion data were collected via 3-dimensional computerized gait analysis before and after the program. Paired t tests were performed on kinematic data for each joint., Results: Significant improvements (P ≤ .008) and large effect sizes (ESs) for sagittal plane hip positions at initial contact and toe-off were found. No differences in pelvic or trunk positioning were determined, although sagittal plane pelvic positioning displayed a trend toward improvement with large ESs. Several trunk variables displayed moderate ESs with a trend toward more upright positioning., Conclusions: Improvements in pelvic and hip joint positioning and more normalized vertical trunk position may indicate increased postural control during gait after 10 sessions of hippotherapy.

Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications.

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (+/- 1.8%) and to MP was 79.0% (+/- 2.1%; P = .004 log rank), although overall survival was 91.9% (+/- 1.4%) and 91.2% (+/- 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m(2) per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m(2) (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.

Aberrant or anomalous anatomy is an under appreciated risk for venous thromboembolic events (VTE). Five adolescents with VTE and predisposing anatomic abnormalities are presented. In three cases, knowledge of the underlying anatomic abnormalities resulted in changes in treatment and management. In two other cases, failure to consider or correct the underlying defect resulted in recurrent thrombosis or post-thrombotic complications. Few case reports are found in the pediatric literature, but a MEDLINE search across all age groups suggests these anomalies are frequently found when appropriate radiological imaging is obtained., ((c) 2008 Wiley-Liss, Inc.)

Stroke is a well-known complication of sickle cell disease (SCD). It is estimated to occur in approximately 11% of patients with SCD by the age of 20. The most frequent cause of cerebrovascular accident (CVA) is blockage of the intracranial internal carotid and middle cerebral arteries. Hemorrhagic stroke is less common, occurring in approximately 3% of children by age 20. Transcranial Doppler (TCD) is the standard test for prediction of stroke risk in children with sickle cell anemia. The authors present a case of a 12-year-old female with SCD transferred to their institution after suffering a catastrophic intracranial hemorrhage. Her most recent TCD was normal 6 months prior to her admission.

Purpose: Aminopterin offers advantages over the related antifolate, methotrexate, including greater potency, complete bioavailability, and more consistent accumulation and metabolism by patients' blasts. This current trial was done to document the toxicity of the aminopterin within a multiagent therapeutic regimen for children with newly diagnosed ALL., Experimental Design: Patients at high risk of relapse were non-randomly assigned to therapy including oral aminopterin 4 mg/m(2), in two doses 12 h apart, in place of methotrexate 100 mg/m(2) in four divided doses., Results: Thirty-two patients, 22 with pre-B ALL and ten with T-lineage ALL, have been treated with aminopterin, with median follow up of 40 months. Hematologic, mucosal and hepatic toxicity has been tolerable and reversible. There have been no toxic deaths among patients in remission. During weekly AMT therapy, higher mean neutrophil counts were observed among patients who were wild type for polymorphisms in methylene tetrahydrofolate reductase and methionine synthase reductase., Conclusions: Aminopterin can be safely incorporated in multiagent therapy for patients with ALL, in place of systemic methotrexate, without causing excessive toxicity. These results support a larger trial comparing the efficacy and toxicity of aminopterin and methotrexate in therapy for patients with ALL.

The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.

Microbacterium sp. AJ115 metabolises a wide range of nitriles using the two-step nitrile hydratase/amidase pathway. In this study, the amidase gene of Microbacterium sp. AJ115 has been inserted into the pCal-n-EK expression vector and expressed in Escherichia coli BL21(DE3)pLysS. The expressed protein is active in E. coli and expression of the amidase gene allows E. coli to grow on acetamide as sole carbon and/or nitrogen source. Expression of active amidase in E. coli was temperature dependent with high activity found when cultures were grown between 20 and 30 degrees C but no activity at 37 degrees C. On induction, the amidase represents 28% of the total soluble protein in E. coli. The expressed amidase has been purified in a single step from the crude lysate using the calmodulin-binding peptide (CBP) affinity tag. The V(max) and K(m) of the purified enzyme with acetamide (50 mM) were 4.4 micromol/min/mg protein and 4.5mM, respectively. The temperature optimum was found to be 50 degrees C. Purified enzyme demonstrated enantioselectivity with the ability to preferentially act on the S enantiomer of racemic (R,S)-2-phenylpropionamide. S-2-phenylpropionic acid is produced with an enantiomeric excess of >82% at 50% conversion of the parent amide.

Tubular epithelial cells (TECs) coexpress Fas and Fas ligand (FasL), which could influence renal allograft injury. While TECs can resist apoptosis by Fas antibody, TEC apoptosis by contact with adjacent TECs has not been studied. Fas expression increased in TECs with cytokine treatment (IFN-gamma, TNF-alpha) while abundant FasL levels were not altered. Apoptosis (Annexin-V, DNA fragmentation) occurred in cytokine-treated TECs monolayers from C3H-HeJ mice by 24 h, but was absent in similarly treated TECs from Fas-deficient (lpr) or FasL-mutant (gld) mice, suggesting that 'self injury' occurred through Fas/FasL. Membrane labeling of TECs in cocultures confirmed that FasL-bearing TECs induced apoptosis when in contact with Fas-bearing TECs. Culturing TECs with allogeneic C57BL/6 (H-2b) splenocytes resulted in apoptosis and elimination of C3H-HeJ TECs by 48 h, with enhanced survival and reduced apoptosis using lpr or gld TECs. In a renal allograft model, survival of C57BL/6 recipients was greater (p < 0.05) and renal function improved (p < 0.001) using C3H-lpr or C3H-gld (H-2 k) donor kidneys compared with C3H-HeJ kidneys. These data demonstrate for the first time that cytokine-activated TECs can injure TECs through expression of functional FasL and Fas. We suggest that inhibition of TEC-TEC 'self injury' may be a novel strategy to augment renal allograft survival.

The role of Fas-FasL interactions in kidney allograft injury may be complex as renal tubular epithelial cells (TEC) express both Fas and FasL. The role and regulation of TEC self-injury has not been investigated. In co-cultures of TEC, FasL-bearing, Fas-null TEC was demonstrated to induce apoptosis of TEC-bearing Fas. Co-culturing effector lpr-TEC (M3.1-lpr) with target WT-TEC (CS3.7) at a ratio of 10:1 (E/T) induced 15.2 +/- 2.4% of target apoptosis as compared to its basal level of 2.6 +/- 0.3%. Similarly lpr-TEC induced apoptosis in gld-TEC (MRM-gld) from a basal level of 3.7 +/- 0.2% to 6.4 +/- 0.3%. Expression of kidney Fas-FasL on injury was tested in a renal transplant model. C57BL/6 (B6) mice were transplanted with Fas-deficient C3H-lpr/lpr or FasL mutation C3H-gld/gld kidneys as compared to normal (wild-type [WT]) C3H/Hej donors. Survival of both lpr and gld recipient was improved compared to WT donors (P <.05) as was function of lpr and gld kidneys indicated by a lower serum creatinine (LPR: 41 +/- 8 micromol/L; GLD: 52 +/- 7 micromol/L) as compared to the WT donors (84 +/- 8 micromol/L, P <.001). These results demonstrate that activated TEC may commit a novel and previously unreported form of self-injury (fractricide) through Fas-FasL. These results suggest that inhibition of renal Fas or FasL might be a useful strategy to prevent TEC loss during rejection.

Purpose: To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine., Patients and Methods: Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered., Results: Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%)., Conclusion: Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.

Neonatal alloimmune thrombocytopenia with intracranial hemorrhage is a reported phenomenon. While most of the hemorrhages are noted to be either intraventricular or intraparenchymal, the authors describe the case of a fourth-ventricle hemorrhage with extension into the spinal column down the cervical spinal cord secondary to maternal anti-human platelet antigen (HPA-1a) antibody.

There is a great variability in the success of horse oocyte maturation and fertilization among laboratories. This study was conducted to determine if the meiotic and developmental competence of horse oocytes could be dependent on the method of oocyte collection, i.e., aspiration of follicular fluid with a vacuum apparatus, or opening follicles and scraping the granulosa layer. Horse oocytes were recovered from abattoir ovaries by aspiration or scraping and classified as having compact (Cp), expanded (Ex), or partial (P) cumuli. In Experiment 1 (Part A in May and Part B in October), oocytes were fixed immediately after collection to assess whether the collection method influenced the initial chromatin configuration of oocytes. In Experiment 2, in vitro maturation rates of oocytes recovered by aspiration or scraping were compared. In Experiment 3, oocytes were matured in vitro and submitted to intracytoplasmic sperm injection (ICSI). Initial chromatin configuration differed according to collection method in that there was a significantly higher prevalence of diffuse chromatin within the germinal vesicle in oocytes recovered by scraping than in oocytes recovered by aspiration (29/87, 33% and 28/166, 17%, respectively; P < 0.01). Maturation of oocytes to metaphase II did not significantly differ between scraped and aspirated oocytes (56/101, 55.4 % vs. 65/106, 61.4%, respectively). The overall pronucleus formation rate after ICSI of oocytes recovered by scraping was not significantly different than that of oocytes recovered by aspiration (50/99, 52.6% vs. 50/85, 68.5 %, respectively); however, the rate of abnormal fertilization was significantly higher for oocytes collected by aspiration (14/73, 19% vs. 6/94, 6%, respectively; P <0.05). These results demonstrate that the collection method affects the population of recovered oocytes and may contribute to differences in results observed among laboratories working with horse oocytes., (Copyright 2001 Wiley-Liss, Inc.)