Functional response of Franklinothrips vespiformis (Thysanoptera: Aeolothripidae) to eggs and nymphs of Bemisia tabaci (Hemiptera: Aleyrodidae).

The Middle East Asia Minor 1 biotype of Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) is a greenhouse and field crop pest of global significance. The objective of this study was to assess the potential of the generalist predatory thrips, Franklinothrips vespiformis Crawford (Thysanoptera: Aeolothripidae), as a biological control agent for B. tabaci. This was achieved by determining the functional responses of F. vespiformis larvae and adults to the egg and nymphal stages of B. tabaci under laboratory conditions. Analyses consisted of 10 replicates of each predator and prey stage combination on bean leaf discs for a 24-h period. Following logistic regression analyses to determine the functional response type exhibited, response parameters were estimated with nonlinear least squares regression using Roger's equation. Results showed that F. vespiformis larvae and adults exhibited a Type II functional response when feeding on immature B. tabaci. The handling times (Th) of F. vespiformis larvae and adults were magnitudes higher for B. tabaci nymphs than they were for eggs, which were in part driven by the higher attack rates (a) observed on eggs. The maximum attack rate (T/Th) for B. tabaci eggs and nymphs exhibited by first-stage larvae, second-stage larvae, and adult F. vespiformis increased with increasing predator age. Results from this study suggest that F. vespiformis larvae and particularly adults are promising biological control agents for B. tabaci and are efficient predators at both low and high prey densities.

Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease.

BACKGROUND: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. METHODS: Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration. RESULTS: Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001). CONCLUSION: Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown. CLINICAL TRIAL: NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

Considerations for Choice of Cranioplasty Material for Pediatric Patients.

INTRODUCTION: Optimal material and timing of cranioplasty in the pediatric population continue to be debated. Autologous and alloplastic materials have various indications for use and risk factors for complications. METHODS: A single-center retrospective cohort study was undertaken of all pediatric patients who underwent cranioplasty with any material from 1991-2021. RESULTS: 149 cranioplasty implants were included. Younger age (6 years old or under), a diagnosis of craniosynostosis as reason for implant, use of autologous bone, and shorter times to cranioplasty were predictive of need for revision surgery. No factors studied had a statistically significant impact on rate of removal of implant at time of revision surgery. CONCLUSION: Autologous and alloplastic cranioplasty materials both have good outcomes with low rates of revision surgery in the pediatric population. Alloplastic implants may be considered in the setting of infection as reason for craniectomy given the lower rate of revision surgery and need for removal. Patients with craniosynostosis as reason for cranioplasty have a higher risk of requiring revision or additional surgeries, regardless of implant used.

Ventriculo-inferior-venacaval shunt salvage via endovascular surgery.

INTRODUCTION: Hydrocephalus treatment can be very challenging. While some hydrocephalic patients can be treated endoscopically, many will require ventricular shunting. Frequent shunt issues over a lifetime is not uncommon. Although most shunt malfunctions are of the ventricular catheter or valve, distal failures occur as well. A subset of patients will accumulate non-functioning distal drainage sites. CASE DESCRIPTION: We present a 27-year-old male with developmental delay who was shunted perinatally for hydrocephalus from intraventricular hemorrhage of prematurity. After failure of the peritoneum, pleura, superior vena cava (SVC), gallbladder, and endoscopy, an inferior vena cava (IVC) shunt was placed minimally-invasively via the common femoral vein. We believe this is only the eighth reported ventriculo-inferior-venacaval shunt. IVC occlusion years later was successfully treated with endovascular angioplasty and stenting followed by anticoagulation. To our knowledge, a ventriculo-inferior-venacaval shunt salvaged by endovascular surgery has not been previously described in the literature. CONCLUSION: After failure of the peritoneum, pleura, SVC, gallbladder, and endoscopy, IVC shunt placement is an option. Subsequent IVC occlusion can be rescued by endovascular angioplasty and stenting. Anticoagulation after stenting (and potentially after initial IVC placement) is advised.

Impact of Low-Dose Computed Tomography and Physician Education on Referral for Head Shape.

Imaging before specialist evaluation of abnormal head shape is associated with a delay in evaluation and an increase in radiation exposure. A retrospective cohort study was performed to identify referral patterns before and after the implementation of a low-dose computed tomography (LDCT) protocol and physician education to examine the intervention's impact on time to evaluation and radiation exposure. Six hundred sixty-nine patients with an abnormal head shape diagnosis at a single academic medical center between July 1, 2014 and December 1, 2019 were reviewed. Demographics, referral information, diagnostic testing, diagnoses, and timeline of clinical evaluation were recorded. Before and after the LDCT and physician education intervention, the average ages at initial specialist appointments were 8.82 and 7.75 months, respectively ( P = 0.125). Children referred after our intervention were less likely to have prereferral imaging than children referred prior (odds ratio: 0.59, CI: 0.39-0.91, P = 0.015). Average radiation exposure per patient before referral decreased from 14.66 mGy to 8.17 mGy ( P = 0.021). Prereferral imaging, referral by a non-pediatrician, and non-Caucasian race were associated with older age at the initial specialist appointment. Widespread craniofacial center adoption of an LDCT protocol and improved clinician knowledge may lead to a reduction in late referrals and radiation exposure in pediatric patients with an abnormal head shape diagnosis.

Predictors and outcomes of respiratory failure among lung transplant patients with COVID-19.

BACKGROUND: There is limited data on the predictors and outcomes of new or worsening respiratory failure among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). METHODS: We included all the LT patients diagnosed with COVID-19 during a 1-year period (March 2020 to February 2021; n = 54; median age: 60, 20-73 years; M:F 37:17). Development of new or worsening respiratory failure (ARF) was the primary outcome variable. RESULTS: The overall incidence of ARF was 48.1% (n = 26). More than 20% of patients (n = 11) needed intubation and mechanical ventilation. Body mass index > 25 Kg/m2 (adjusted OR: 5.7, .99-32.93; P = .05) and peak D-dimer levels > .95 mcg/ml (adjusted OR: 24.99, 1.77-353.8; P = .017) were independently associated with ARF while anticoagulation use prior to COVID-19 was protective (adjusted OR: .024, .001-.55; P = .02). Majority patients survived the acute illness (85.2%). Pre-infection chronic lung allograft dysfunction (CLAD) was an independent predictor of mortality (adjusted HR: 5.03, 1.14-22.25; P = .033). CONCLUSIONS: COVID-19 is associated with significant morbidity and mortality among LT patients. Patients on chronic anticoagulation seem to enjoy favorable outcomes, while higher BMI and peak D-dimer levels are associated with development of ARF. Pre-infection CLAD is associated with an increased risk of death from COVID-19.

Characteristics and outcomes among vaccinated lung transplant patients with breakthrough COVID-19.

BACKGROUND: Despite multiple studies evaluating the immunological responsiveness to vaccines, the clinical effectiveness of the two-dose mRNA vaccine schedule among lung transplant (LT) patients has not been evaluated. METHODS: We included LT patients who tested positive for SARS-CoV-2 on a nasopharyngeal swab between March 1, 2020, and August 25, 2021 (n = 70). The study group was divided based on their vaccination status. RESULTS: During the study period, 14 fully vaccinated LT patients with one of the mRNA vaccines tested positive for COVID-19 (median age 54, range 30-62 years, M:F 9:5). The vaccinated cohort was younger with bilateral LT, have suppurative conditions as the transplant indication, and present with milder symptoms. However, pulmonary parenchymal involvement was seen among all 12 patients where computed tomography (CT) of chest was available. The laboratory profile indicated a more subdued inflammatory response among the vaccinated group. A lower proportion of vaccinated patients developed respiratory failure, needed ICU admission or ventilator support, although none of the differences achieved statistical significance. None of the vaccinated patients succumbed to COVID-19 during the study period, while the 4-week mortality among unvaccinated patients was nearly 15% (8/56). CONCLUSIONS: In this cohort of vaccinated LT patients who developed breakthrough COVID-19, the clinical course, risk of complications, and outcomes trended better than unvaccinated patients. However, universal involvement of the allograft demonstrates the continued vulnerability of these patients to significant sequelae from COVID-19. Future studies may evaluate the incremental protection of vaccination after the completion of the third dose of mRNA vaccines among LT patients.

Reductive carboxylation supports redox homeostasis during anchorage-independent growth.

Cells receive growth and survival stimuli through their attachment to an extracellular matrix (ECM). Overcoming the addiction to ECM-induced signals is required for anchorage-independent growth, a property of most malignant cells. Detachment from ECM is associated with enhanced production of reactive oxygen species (ROS) owing to altered glucose metabolism. Here we identify an unconventional pathway that supports redox homeostasis and growth during adaptation to anchorage independence. We observed that detachment from monolayer culture and growth as anchorage-independent tumour spheroids was accompanied by changes in both glucose and glutamine metabolism. Specifically, oxidation of both nutrients was suppressed in spheroids, whereas reductive formation of citrate from glutamine was enhanced. Reductive glutamine metabolism was highly dependent on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor. This activity occurred in absence of hypoxia, a well-known inducer of reductive metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and suppressing IDH1 reduced spheroid growth through a mechanism requiring mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate produced reductively in the cytosol could enter the mitochondria and participate in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth. Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the mitochondrial citrate transporter protein. Together, the data indicate that adaptation to anchorage independence requires a fundamental change in citrate metabolism, initiated by IDH1-dependent reductive carboxylation and culminating in suppression of mitochondrial ROS.

Barriers and facilitators of health among older adult immigrants in the United States: an integrative review of 20 years of literature.

BACKGROUND: There are over seven million older adult immigrants in the United States, and that number is expected to increase. Older adult immigrants in the United States have unique factors that influence their health. METHODS: In this integrative review, we systematically review 20 years of peer-reviewed literature on the barriers (i.e. isolation, lack of English Language Proficiency, low health literacy, lack of SES resources, discrimination) and facilitators (i.e. English Language Proficiency and maintaining ones native language, social support, culturally sensitive providers, healthcare access) of health among older adult immigrants in the United States. RESULTS: We found differing uses of the term 'older adult', emphasis on the lack of homogeneity among older adult immigrants, social support and isolation as significant barriers and facilitators of older adult immigrant health, and inconsistencies in uses and definitions of acculturation. We also examined relevant theories in the literature. Based on the literature review, focusing on Acculturation Theory, Social Cognitive Theory, and Successful Aging Theory, combining these three theories with findings from the literature to create the Older Adult Immigrant Adapted Model for Health Promotion. CONCLUSIONS: Public health strives to promote health and prevent adverse health outcomes. Our integrative review not only systematically and thoroughly explicates 20 years of literature, but the Older Adult Immigrant Adapted Model for Health Promotion, provides guidance for future research and interventions.

Pediatric craniosynostosis computed tomography: an institutional experience in reducing radiation dose while maintaining diagnostic image quality.

BACKGROUND: Children with craniosynostosis may undergo multiple computed tomography (CT) examinations for diagnosis and post-treatment follow-up, resulting in cumulative radiation exposure. OBJECTIVE: To reduce the risks associated with radiation exposure, we evaluated the compliance, radiation dose reduction and clinical image quality of a lower-dose CT protocol for pediatric craniosynostosis implemented at our institution. MATERIALS AND METHODS: The standard of care at our institution was modified to replace pediatric head CT protocols with a lower-dose CT protocol utilizing 100 kV, 5 mAs and iterative reconstruction. Study-ordered, protocol-utilized and radiation-dose indices were collected for studies performed with routine pediatric brain protocols (n=22) and with the lower-dose CT protocol (n=135). Two pediatric neuroradiologists evaluated image quality in a subset (n=50) of the lower-dose CT studies by scoring visualization of cranial structures, confidence of diagnosis and the need for more radiation dose. RESULTS: During the 30-month period, the lower-dose CT protocol had high compliance, with 2/137 studies performed with routine brain protocols. With the lower-dose CT protocol, volume CT dose index (CTDIvol) was 1.1 mGy for all patients (0-9 years old) and effective dose ranged from 0.06 to 0.22 mSv, comparable to a 4-view skull radiography examination. CTDIvol was reduced by 98% and effective dose was reduced up to 67-fold. Confidence in diagnosing craniosynostosis was high and more radiation dose was considered unnecessary in all studies (n=50) by both radiologists. CONCLUSION: Replacing the routine pediatric brain CT protocol with a lower-dose CT craniosynostosis protocol substantially reduced radiation exposure without compromising image quality or diagnostic confidence.

A qualitative analysis of perceptions of and reactions to COVID-19.

OBJECTIVE: To understand communities' perceptions, beliefs, and health-related behavior choices related to COVID-19 in order to guide public health nursing communication and interaction with patients and the community. DESIGN: A qualitative study, guided by the Health Belief Model (HBM), strove to comprehend the perceptions and reactions to COVID-19 among Wisconsinites. SAMPLE: Twenty-five diverse Wisconsin residents aged 18 or older. MEASUREMENTS: Semi-structured interviews provided information about individuals' attitudes, perceptions, and reactions to COVID-19. Interviews were audio-recorded, transcribed, and thematic analysis was conducted to identify themes. RESULTS: We identified three major themes: (1) "health care starts way before you ever enter the doors of a healthcare facility"; (2) "to live in a society is to help each other"; and (3) mental health as impacted by COVID-19. CONCLUSIONS: This study demonstrated the need for greater public health support, as well as the role of Social Determinants of Health. Understanding perceptions and reactions to COVID-19 can help public health nurses understand and better respond to future pandemics.

Pride Camp: Pilot study of an intervention to develop resilience and self-esteem among LGBTQ youth.

BACKGROUND: Many LGBTQ youth experience rejection and discrimination in their families and schools, and the range of interventions for improving their resilience and well-being is limited. We developed and piloted an LGBTQ-youth-focused intervention to build resilience and promote health equity, called Pride Camp, in an urban environment in the Midwest. METHODS: Using a mixed-method approach we examined the impact of Pride Camp on resilience and other measures of well-being among LGBTQ high school students who attended camp on a college campus in 2015, 2016, and 2017. Camp attendees and the research sample included a majority proportion of transgender and gender nonbinary (TGN) youth. RESULTS: Pre- and post-test data from our quantitative surveys (n = 28), indicated significant increases in resilience, self-esteem, and quality of life in LGBTQ youth who attended camp. Similar results were found among the TGN participants (n = 19). Qualitative data from focus groups indicated that specifically for TGN youth, the affirming environment at the camp provided social opportunities that they had not found elsewhere. CONCLUSIONS: Findings suggest that the Pride Camp intervention provides a platform for LGBTQ youth to meet peers and engage in LGBTQ communities, improving their resilience and outlook on the future. A larger controlled study of the Pride Camp intervention including measurement of additional specific health outcomes over a longer follow-up period is warranted to examine the impact of this program on health equity.

Post-infection pulmonary sequelae after COVID-19 among patients with lung transplantation.

BACKGROUND: There is limited data on outcomes among lung transplant (LT) patients who survive Coronavirus disease 2019 (COVID-19). METHODS: Any single or bilateral LT patients who tested positive for SARS-CoV-2 between March 1, 2020, to February 15, 2021 (n = 54) and survived the acute illness were included (final n = 44). Each patient completed at least 3 months of follow-up (median: 4.5; range 3-12 months) after their index hospitalization for COVID-19. The primary endpoint was a significant loss of lung functions (defined as > 10% decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1 ) on two spirometries, at least 3 weeks apart compared to the pre-infection baseline). RESULTS: A majority of the COVID-19 survivors had persistent parenchymal opacities (n = 29, 65.9%) on post-infection CT chest. Patients had significantly impaired functional status, with the majority reporting residual disabilities (Karnofsky performance scale score of 70% or worse; n = 32, 72.7%). A significant loss of lung function was observed among 18 patients (40.9%). Three patients met the criteria for new chronic lung allograft dysfunction (CLAD) following COVID-19 (5.6%), with all three demonstrating restrictive allograft syndrome phenotype. An absolute lymphocyte count < 0.6 × 103 /dl and ferritin > 150 ng/ml at the time of hospital discharge was independently associated with significant lung function loss. CONCLUSIONS: A significant proportion of COVID-19 survivors suffer persistent allograft injury. Low absolute lymphocyte counts (ALC) and elevated ferritin levels at the conclusion of the hospital course may provide useful prognostic information and form the basis of a customized strategy for ongoing monitoring and management of allograft dysfunction. TWEET: Twitter handle: @AmitBangaMD Lung transplant patients who survive COVID-19 suffer significant morbidity with persistent pulmonary opacities, loss of lung functions, and functional deficits. Residual elevation of the inflammatory markers is predictive.

Comparison of Perioperative Outcomes and Parental Satisfaction Outcomes of Strip Craniectomy with Postoperative Helmet versus Spring-Mediated Remodeling in Sagittal Craniosynostosis.

INTRODUCTION: We sought to compare outcomes and parental satisfaction between 2 approaches for sagittal craniosynostosis: strip craniectomy with spring-mediated skull remodeling (SMSR) and strip craniectomy with postoperative helmet (SCH). METHODS: Perioperative and outcome data for SMSR or SCH patients between September 2010 and July 2019 were retrospectively reviewed. A telephone survey was administered to parents of children who underwent both procedures. RESULTS: A total of 62 children were treated for sagittal craniosynostosis by either SMSR (n = 45) or SCH (n = 17). The SCH group had a lower estimated blood loss (27 vs. 47.06 mL, p = 0.021) and age at surgery (13.0 vs. 19.8 weeks) than the SMSR group. Three patients underwent early springs removal due to trauma or dislodgement, all of whom converted to helmeting. Of the 62 children initially identified, 59 were determined to have an adequate follow-up time to assess long-term outcomes. The mean follow-up time was 30.1 months (n = 16) in the SCH group and 32.0 months in the SMSR group (n = 43, p = 0.39). Two patients in the SCH group and one in the SMSR group converted to open cranial vault reconstruction. Thirty parents agreed to respond to the satisfaction survey (8 SCH, 22 SMSR) based on a Likert scale of responses (0 being most dissatisfied possible, 4 most satisfied possible). Average satisfaction was 3.86/4.0 in the SCH group and 3.45/4.0 in the SMSR group. No parents in the SCH group would change to SMSR, while 3 of the 22 SMSR survey responders would have changed to SCH. CONCLUSIONS: Perioperative outcomes and average parental satisfaction were similar in both groups. Importance of helmet wear compliance and risk of spring dislodgement should be discussed with parents.

Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium.

In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of ß2 glycoprotein I promotes thrombosis, and preclinical studies indicate that this is due to endothelial nitric oxide synthase (eNOS) antagonism via apolipoprotein E receptor 2 (apoER2)-dependent processes. How apoER2 molecularly links these events is unknown. Here, we show that, in endothelial cells, the apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of the heterotrimeric protein phosphatase 2A (PP2A). Disabled-2 (Dab2) recruitment to the apoER2 NPXY motif promotes the activating L309 methylation of the PP2A catalytic subunit by leucine methyl transferase-1. Concurrently, Src homology domain-containing transforming protein 1 (SHC1) recruits the PP2A scaffolding subunit to the proline-rich apoER2 C terminus along with 2 distinct regulatory PP2A subunits that mediate inhibitory dephosphorylation of Akt and eNOS. In mice, the coupling of these processes in endothelium is demonstrated to underlie aPL-invoked thrombosis. By elucidating these intricacies in the pathogenesis of APS-related thrombosis, numerous potential new therapeutic targets have been identified.

Comparison of the phytoseiid mites Amblyseius swirskii and Amblydromalus limonicus for biological control of chilli thrips, Scirtothrips dorsalis (Thysanoptera: Thripidae).

The chilli thrips, Scirtothrips dorsalis Hood, is a recently established pest in the USA and poses a serious risk to many economically important ornamental and food crops. In this study the biological control potential of the phytoseiid mites Amblydromalus limonicus (Garman and McGregor) and Amblyseius swirskii (Athias-Henriot) was compared by examining their predation and oviposition rates when fed different developmental stages of S. dorsalis. Gravid females were offered 10 individuals of either first instar, second instar, or adult S. dorsalis using a no-choice leaf disc bioassay and oviposition and predation rates were assessed daily for 2 and 3 days, respectively. There was no significant difference in predation and oviposition rates between mite species fed specific S. dorsalis life stages. There was, however, a significant effect of S. dorsalis life stage on the oviposition and predation rates observed for each mite species. The larval stage was the most preferred stage for both mite species, with A. swirskii consuming 4.6-6.3 and A. limonicus 4.8-6.4 individuals/day compared to only 1.6-1.7 adults/day consumed by both species. Female A. swirskii and A. limonicus laid 0.55-0.75 and 0.73 eggs/day on the two larval stages, respectively, compared to only 0.25-0.30 eggs/day observed for individuals feeding on adults. Although the results showed that the biological control potential of both mite species was similar, having an additional predator available that may be as effective as A. swirskii, a proven control agent against S. dorsalis in the field, warrants additional research into its potential utility.

Culture, identity, strength and spirituality: A qualitative study to understand experiences of African American women breast cancer survivors and recommendations for intervention development.

OBJECTIVE: Despite advancements in cancer treatment, racial disparities in breast cancer survival persist, with African American women experiencing lower survival rates and poorer quality of life than non-Hispanic White women. Using a social cognitive model of restorative well-being as a framework, this qualitative study sought: (a) to examine strength- and culture-related factors associated with African American female breast cancer survivors' cancer coping and post-treatment experiences and (b) to make recommendations for culturally sensitive intervention. METHODS: Eight focus groups occurred with a total of 40 local African American breast cancer survivors. Focus groups were audiotaped and transcribed verbatim. Framework analyses were used to identify themes. NVivo qualitative analysis software-managed data. RESULTS: Two major themes emerged from the focus group discussions: (a) God enables breast cancer survivorship and works every day in our lives and (b) the healthiest thing about us is that we are strong African American women. Recommendations for intervention planning and implementation were made towards intervention structure, content development and language framing in a local context. CONCLUSION: Findings suggest a need for community-based participatory survivorship interventions that are culturally and spiritually consonant and peer-based. Such interventions may respond to the cancer-related and personal needs of the target population.

RasGRF Couples Nox4-Dependent Endoplasmic Reticulum Signaling to Ras.

OBJECTIVES: In response to endoplasmic reticulum (ER) stress, endothelial cells initiate corrective pathways such as the unfolded protein response. Recent studies suggest that reactive oxygen species produced on the ER may participate in homeostatic signaling through Ras in response to ER stress. We sought to identify mechanisms responsible for this focal signaling pathway. APPROACH AND RESULTS: In endothelial cells, we found that ER stress induced by tunicamycin activates the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 focally on the ER surface but not on the plasma membrane. Ras activation is also restricted to the ER, occurs downstream of Nox4, and is required for activation of the unfolded protein response. In contrast, treatment with the growth factor VEGF (vascular endothelial growth factor) results in Ras activation and reactive oxygen species production confined instead to the plasma membrane and not to the ER, demonstrating local coupling of reactive oxygen species and Ras signals. We further identify the calcium-responsive, ER-resident guanyl exchange factors RasGRF1 and RasGRF2 as novel upstream mediators linking Nox4 with Ras activation in response to ER stress. Oxidation of the sarcoendoplasmic reticulum calcium ATPase and increases in cytosolic calcium caused by ER stress are blocked by Nox4 knockdown, and reduction in cytosolic free calcium prevents both Ras activation and the unfolded protein response. CONCLUSIONS: ER stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF.

Perceived Risk of Intimate Partner Violence Among STI Clinic Patients: Implications for Partner Notification and Patient-Delivered Partner Therapy.

Patient-delivered partner therapy (PDPT) is the practice of providing patients diagnosed with a bacterial sexually transmitted infection (STI) medication to give directly to their partner for treatment without requiring the partner to participate in diagnostic testing and counseling. Despite a growing body of evidence in support of PDPT, literature is limited to date on the influence of perceived risk of intimate partner violence (IPV) on PDPT use. We analyzed mixed-method data from 196 quantitative surveys (61% male, M age = 31.2, 92% Black or African-American) and 25 qualitative interviews to better understand the barriers and facilitators associated with PDPT delivery for patients attending a Midwestern, publicly funded STI clinic in the U.S. Nearly a third of surveyed patients (29; 34% of women, 26% of men) expressed worry about IPV when delivering PDPT. Patients had concerns about infidelity worry, embarrassment, and anxiety (referred to as IWEA hereafter) associated with partner notification and PDPT delivery. We found IWEA was highly correlated with IPV concerns in a fully adjusted logistic regression model. Women had 2.43 (95% CI = 1.09-5.42) times greater odds of worrying about IPV than men; other significant factors associated with IPV worry included higher condom use, no prior STI diagnosis, and being uninsured (as compared to having Medicare/Medicaid insurance). Encouraging communication between healthcare providers and their patients about the potential for IPV could facilitate patient triaging that results in the consideration of alternative partner referral mechanisms for patients or partners at risk of harm and better outcomes for patients and their partners.

A Retrospective Study of Cervical Spine MRI Findings in Children with Abusive Head Trauma.

BACKGROUND/AIMS: Increasing attention has been given to the possible association of cervical spine (c-spine) injuries with abusive head trauma (AHT). The aims of this study were to describe c-spine MRI findings in hospitalized AHT patients. METHODS: This is a retrospective study of children under the age of 5 years with AHT admitted to hospital in 2004-2013. Those with c-spine MRI were identified, and the images were reviewed. RESULTS: 250 AHT cases were identified, with 34 (14%) undergoing c-spine MRI. Eleven patients (32%) had 25 findings, including hematoma in 2, occiput-C1-C2 edema in 3, prevertebral edema in 6, facet edema in 2, and interspinous and/or muscular edema in 10. No patients had a clinically evident c-spine injury, a clinically unstable c-spine, or required c-spine surgery. CONCLUSIONS: C-spine MRI may identify abnormalities not apparent upon physical examination and the procedure should therefore be considered in cases of suspected AHT.