Search

Background: Intraoperative molecular imaging (IMI) uses a cancer-targeted fluorescent agent injected into patients to localize tumor nodules. Pafolacianine is a folate receptor (FR)–targeted near-infrared fluorescent probe. Almost 10% of patients have false negative fluorescence findings intraoperatively. We hypothesized that tumor histology explains why lung cancer may not fluoresce. Methods: Adenocarcinoma (AC) (A549, LKR) and squamous cell carcinoma (SCC) (H127, H1264) cell lines were stained with pafolacianine. Near-infrared fluorescent microscopy was used to quantify mean fluorescence intensity. Tissue microarray slides of patients with AC and SCC were evaluated by immunohistochemistry for FR alpha (FRα) and beta (FRβ) expression. Finally, we retrospectively analyzed IMI data from clinical trials of patients with AC and SCC receiving pafolacianine. Results: AC (intensity 30.31) cell lines have a higher fluorescence intensity than SCC cell lines (intensity 5.4) (P < .001). On slide analysis, 93.8% of ACs expressed FRα compared with 44.4% of SCCs (P = .002). Finally, there were 326 patients enrolled in clinical trials: 211 had lesions localized in vivo, and 134 of these patients had pure AC or SCC. All 9 patients with SCC have a positive smoking history and a mean pack-year of 60.2 (SD 3,6), whereas 76% of patients with AC have a history of smoking and a mean pack-year of 29.3 (P = .02). The odds ratio for fluorescence of (AC/SCC) was 2.05 (P = .004) and 2.01 (P = .02) on univariate and multivariate logistic regression, respectively. Conclusions: During IMI with pafolacianine, a nonfluorescent nodule is more likely to be SCC than AC. AC has a high probability of fluorescing because of higher expression of FRα or FRβ, or both.

We present a series of temperature and field-dependent magnetization studies of large single-crystal spin glass samples, focusing on both field-cooled (FC) and zero-field-cooled (ZFC) magnetization studies, as well as ac susceptibility measurements. Using the above experimental techniques we aim to understand the nature of spin glass transition in presence of a field, a key factor in understanding the properties of these systems. Building on previous studies that have explored magnetic signatures indicative of spin glass transitions, our research employs a systematic approach to refine the identification of this transition temperature. Through static and dynamic measurements, we aim to shed light on the open issues regarding the key markers of spin glass transitions, enhancing our understanding of these complex systems.

The increasing demand for natural products in the United States reflects a cultural shift towards health and sustainability. This trend infiltrates consumer sectors such as the sunscreen industry, amidst concerns about health and environmental impacts of chemical ingredients. The Hawaii Sunscreen Ban has intensified sunscreen formula safety discussions, particularly regarding butylparaben, oxybenzone, and octinoxate. Even at low concentrations, these compounds bleach hard corals eventually leading to their death. As well, these chemicals pose threats to marine ecosystems and raise concerns about human health, particularly systemic absorption and the possibility of causing endocrine disruption. While some argue for chemical-based sunscreens for skin cancer prevention, others advocate for mineral-based alternatives that avoid harmful ingredients. However, public opinion on sunscreen varies, influenced by adverse reactions, socioeconomic status, gender, and cultural perceptions. Future studies should explore diverse demographic perspectives and long-term health and environmental impacts of products containing potentially toxic ingredients. As well, effective communication strategies to promote sunscreen safety and encourage sustainable sun protection practices is needed.

Abstract Increasing evidence has demonstrated that drug resistance can be acquired in cancer cells by kinase rewiring, which is an obstacle for efficient cancer therapy. However, it is technically challenging to measure the expression of protein kinases on large scale due to their dynamic range in human proteome. We employ a lysine-targeted sulfonyl fluoride probe, named XO44, which binds to 133 endogenous kinases in intact lenvatinib-resistant hepatocellular carcinoma (HCC) cells. This analysis reveals cyclin-dependent kinase 6 (CDK6) upregulation, which is mediated by ERK/YAP1 signaling cascade. Functional analyses show that CDK6 is crucial in regulation of acquired lenvatinib resistance in HCC via augmentation of liver cancer stem cells with clinical significance. We identify a noncanonical pathway of CDK6 in which it binds and regulates the activity of GSK3β, leading to activation of Wnt/β-catenin signaling. Consistently, CDK6 inhibition by palbociclib or degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with lenvatinib in vitro. Interestingly, palbociclib not only exerts maximal growth suppressive effect with lenvatinib in lenvatinib-resistant HCC models but also reshapes the tumor immune microenvironment. Together, we unveil CDK6 as a druggable target in lenvatinib-resistant HCC and highlight the use of a chemical biology approach to understand nongenetic resistance mechanisms in cancer.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and has a poor prognosis. Although immune checkpoint inhibitors have entered a new era of HCC treatment, their response rates are modest, which can be attributed to the immunosuppressive tumor microenvironment within HCC tumors. Accumulating evidence has shown that tumor growth is fueled by cancer stem cells (CSCs), which contribute to therapeutic resistance to the above treatments. Given that CSCs can regulate cellular and physical factors within the tumor niche by secreting various soluble factors in a paracrine manner, there have been increasing efforts toward understanding the roles of CSC-derived secretory factors in creating an immunosuppressive tumor microenvironment. In this review, we provide an update on how these secretory factors, including growth factors, cytokines, chemokines, and exosomes, contribute to the immunosuppressive TME, which leads to immune resistance. In addition, we present current therapeutic strategies targeting CSC-derived secretory factors and describe future perspectives. In summary, a better understanding of CSC biology in the TME provides a rational therapeutic basis for combination therapy with ICIs for effective HCC treatment.

Abstract Background Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience. Methods This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022. Our patients underwent standard of care PD in addition to tracheostomy and gastrostomy/jejunostomy tube with therapeutic anticoagulation (AC) leading up to surgery. Measured outcomes were postoperative PNA, DVT, and sepsis. The predicted risk of those same outcomes had patients not undergone the interventions was calculated based on the American College of Surgeons (ACS) surgical risk calculator (SRC). A McNemar's test was used to determine whether the risk of having PNA, DVT and sepsis differed between the two subgroups. Results Fifty‐five patients were included in the study. The mean age was 70 years (SD 6.2) with a mean of 21 (SD 19) pack‐years of smoking. PNA, DVT, and catheter‐related sepsis occurred in 12, four, and seven patients, respectively. Upon using the ACS SRC prediction model of the nonintervention group, PNA, DVT and catheter related sepsis was predicted to occur in 24 (paired data OR 5, 95% CI: 1.4–17.2; McNemar's test p = 0.008), 14 (paired data OR 3.5, 95% CI: 1.15–10.6; McNemar's test p = 0.03), and 17 (paired OR 3, 95% CI: 1.09–8.3; McNemar's test p = 0.04) patients, respectively. Discussion Patients undergoing tracheostomy creation, therapeutic AC at the time of diagnosis, and gastrostomy tube placement had a reduced risk of aspiration PNA, DVT, and catheter sepsis.

Summary: The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype.

Abstract Background Malignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM. Methods The NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t‐test and independent‐samples proportions test were used for means analysis. Survival was assessed by the Kaplan–Meier method using SPSS version 28. Results A total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p

Abstract Background ‘Tele-Mental Health (MH) services,’ are an increasingly important way to expand care to underserved groups in low-resource settings. In order to continue providing psychiatric, psychotherapeutic and counselling care during COVID-19-related movement restrictions, Médecins Sans Frontières (MSF), a humanitarian medical organization, abruptly transitioned part of its MH activities across humanitarian and resource-constrained settings to remote format. Methods From June–July of 2020, investigators used a mixed method, sequential explanatory study design to assess MSF staff perceptions of tele-MH services. Preliminary quantitative results influenced qualitative question guide design. Eighty-one quantitative online questionnaires were collected and a subset of 13 qualitative follow-up in-depth interviews occurred. Results Respondents in 44 countries (6 geographic regions), mostly from Sub-Saharan Africa (39.5%), the Middle East and North Africa (18.5%) and Asia (13.6%) participated. Most tele-MH interventions depended on audio-only platforms (80%). 30% of respondents reported that more than half of their patients were unreachable using these interventions, usually because of poor network coverage (73.8%), a lack of communication devices (72.1%), or a lack of a private space at home (67.2%). Nearly half (47.5%) of respondents felt their staff had a decreased ability to provide comprehensive MH care using telecommunication platforms. Most respondents thought MH staff had a negative (46%) or mixed (42%) impression of remote care. Nevertheless, almost all respondents (96.7%) thought tele-MH services had some degree of usefulness, notably improved access to care (37.7%) and time efficiency (32.8%). Qualitative results outlined a myriad of challenges, notably in establishing therapeutic alliance, providing care for vulnerable populations and those inherent to the communications infrastructure. Conclusion Tele-MH services were perceived to be a feasible alternative solution to in-person therapeutic interventions in humanitarian settings during the COVID-19 pandemic. However, they were not considered suitable for all patients in the contexts studied, especially survivors of sexual or interpersonal violence, pediatric and geriatric cases, and patients with severe MH conditions. Audio-only technologies that lacked non-verbal cues were particularly challenging and made risk assessment and emergency care more difficult. Prior to considering tele-MH services, communications infrastructure should be assessed, and comprehensive, context-specific protocols should be developed.

Abstract Background Specialised mental health (MH) care providers are often absent or scarcely available in low resource and humanitarian settings (LRHS), making MH training and supervision for general health care workers (using task-sharing approaches) essential to scaling up services and reducing the treatment gap for severe and common MH conditions. Yet, the diversity of settings, population types, and professional skills in crisis contexts complicate these efforts. A standardised, field tested instrument for clinical supervision would be a significant step towards attaining quality standards in MH care worldwide. Methods A competency-based clinical supervision tool was designed by Médecins Sans Frontières (MSF) for use in LRHS. A systematic literature review informed its design and assured its focus on key clinical competencies. An initial pool of behavioural indicators was identified through a rational theoretical scale construction approach, tested through waves of simulation and reviewed by 12 MH supervisors in seven projects where MSF provides care for severe and common MH conditions. Results Qualitative analysis yielded two sets of competency grids based on a supervisee's professional background: one for ‘psychological/counselling’ and another for ‘psychiatric/mhGAP’ practitioners. Each grid features 22–26 competencies, plus optional items for specific interventions. While the structure and content were assessed as logical by supervisors, there were concerns regarding the adequacy of the tool to field reality. Conclusions Humanitarian settings have specific needs that require careful consideration when developing capacity-building strategies. Clinical supervision of key competencies through a standardised instrument represents an important step towards ensuring progress of clinical skills among MH practitioners.

Carbon curing or mixing in concrete is promising for carbon dioxide sequestration. Here, the authors show that the increased use of binder material to compensate the loss in compressive strength and electricity for carbon dioxide curing is more likely to increase carbon dioxide emissions on a life cycle basis for carbon cured or mixed concrete.

Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are associated with severe intestinal disorders and combined immunodeficiency (CID), with poor long-term survival. This study describes the characteristics and clinical course of six patients with intestinal failure who were found to have biallelic TTC7A mutations, highlighting key management strategies for identifying these patients and improving their survival. Of the six patients included, five had multiple intestinal atresias (83%) and one had congenital enteropathy (17%). Pyloric web or atresia was present in 100% of patients. All patients had low CD3+ T-cell counts on flow cytometry, consistent with CID. Immunologic management consisted of intravenous immunoglobulin and antibiotic prophylaxis, while two patients (33%) underwent stem cell transplantation. All patients were initially dependent on parenteral nutrition, but two (33%) achieved enteral autonomy after undergoing intestinal transplantation. Patients were followed for a median of 7 years (IQR 4.75–9.25), with a long-term survival rate of 67%. The high incidence of pyloric atresia in this case series suggests that the presence of pyloric atresia, especially in the setting of other intestinal disorders, should prompt screening for CID and a genetic evaluation. Recognition of the mutation and involvement of appropriate interdisciplinary care teams are essential for optimizing survival of these complex patients.

Abstract Founded in 1993, the Yellowstone to Yukon (Y2Y) vision was one of the earliest large‐landscape conservation visions. Despite growing recognition of large‐landscape conservation strategies, there have been few tests to date of conservation gains achieved through such approaches. We tested for conservation gains in the Y2Y region of North America following initiation of the Y2Y conservation vision in 1993 using a counterfactual spatiotemporal comparison and tracking change in five different conservation metrics. First, we enumerated the area of land within Y2Y in designated protected areas. We then compared the rate of change of protected area growth before‐ and after‐initiation of Y2Y in 1993 and to two adjacent counterfactual regions. Protected areas in the Y2Y grew by 7.8%, increasing by 107,289 km2, exceeding the Aichi target of 17% of the area under protection by 2018. More importantly, the rate of protected area growth increased 90% following initiation of the Y2Y large‐landscape conservation vision in 1993, whereas protected area growth declined in adjacent regions, or remained constant throughout North America. Sustained growth in protected areas and private land conservation was complemented by expansion of endangered grizzly bears in the U.S. portion of Y2Y, the greatest global expansion from zero to at least 117 wildlife road‐crossing structures and growing mainstreaming coverage of the Y2Y vision. Our counterfactual comparison provides valuable evidence that large‐landscape conservation strategies such as Y2Y can enhance protected area growth and other conservation metrics. We conclude that large‐landscape conservation strategies may be a useful model for achieving global large‐landscape conservation and biodiversity conservation targets.

Aim. This study aims to examine which factors influence the distance traveled by patients for inpatient care in Kenya. Methods. We used data from the fourth round of the Kenya Household Health Expenditure and Utilization survey. Our dependent variable was the self-reported distance traveled by patients to access inpatient care at public health facilities. As the clustered data were correlated, we used the generalized estimating equations approach with an exchangeable correlation under a Tweedie distribution. To select the best-fit covariates for predicting distance, we adopted a variable selection technique using the QICu and R2 criteria, wherein the lowest (highest) value for the former (latter) is preferred. Results. Using data for 451 participants from 47 counties, we found that three-fifths were admitted between 1 and 5 days, two-thirds resided in rural areas, and 90% were satisfied with the facilities’ service. Wealth quintiles were evenly distributed across respondents. Most admissions (81%) comprised 65, and 25–54 years. Many households were of medium size (4–6 members) and had low education level (48%), and nine-tenths had no access to insurance. While two-thirds reported employment-based income, the same number reported not having cash to pay for inpatient services; 6 out of 10 paid over 3000 KES. Thus, differences in employment, ability to pay, and household size influence the distance traveled to access government healthcare facilities in Kenya. Interpretation. Low-income individuals more likely have large households and live in rural areas and, thus, are forced to travel farther to access inpatient care. Unlike the unemployed, the employed may have better socioeconomic status and possibly live near inpatient healthcare facilities, thereby explaining their short distances to access these services. Policymakers must support equal access to inpatient services, prioritize rural areas, open job opportunities, and encourage smaller families.

The transition to electric vehicles (EVs) will impact the climate, the environment, and society in highly significant ways. This study compares EVs to vehicles with internal combustion engines for three major areas: greenhouse gas emissions (GHGs), fuel costs, and transportation energy burden (i.e. percentage of income spent on vehicle fuels). Excluded in the analysis is the purchase cost of the vehicles themselves. The results reveal that over 90% of vehicle-owning U.S. households would see reductions in both GHGs and transportation energy burden by adopting an EV. For 60% of households these savings would be moderate to high (i.e. >2.3 metric tons of CO _2 e reduction per household annually and >0.6% of energy burden reduction). These reductions are especially pronounced in the American West (e.g. California, Washington) and parts of the Northeast (e.g. New York) primarily due to a varying combination of cleaner electricity grids, lower electricity prices (relative to gas prices), and smaller drive-cycle and temperature-related impacts on fuel efficiency. Moreover, adopting an EV would more than double the percentage of households that enjoy a low transportation energy burden (4% income spent on fuel annually), and if at-home charging is unavailable, this rises to over 75 percent. Addressing this inequity hinges on three major interventions: 1) targeted policies to promote energy justice in lower-income communities, including subsidizing charging infrastructure; 2) strategies to reduce electricity costs; and 3) expanding access to low-carbon transport infrastructure (e.g. public transit, biking, and car sharing).

Objective: This study aimed to identify the factors associated with outpatient expenses incurred by households in Kenya.Background: The problem of outpatient healthcare expenses incurred by citizens in countries with limited resources has received little attention. Thus, this study aimed to determine the predictors of household spending on outpatient expenses in Kenya.Method: We conducted a cross-sectional analysis on households in Kenya using data from the 2018 Kenya Household Health Expenditure and Utilization Survey. We applied the generalized estimating equations method to determine the best subset of predictors of outpatient care cost.Findings: The best predictors of outpatient care expenses in Kenya are age, wealth index, and education level of the household head.Conclusions: There were no differences regarding age in the mean spending on outpatient care. Moreover, we found that the cost of outpatient care changes with age in a sinusoidal manner. We observed that rich households spent more on outpatient care, mostly owing to their financial ability. Households whose heads reported primary or secondary school education level spent less on outpatient costs than households headed by those who never went to school.

The neurobiological mechanisms that mediate psychiatric comorbidities associated with metabolic disorders such as obesity, metabolic syndrome and diabetes remain obscure. High fructose corn syrup (HFCS) is widely used in beverages and is often included in food products with moderate or high fat content that have been linked to many serious health issues including diabetes and obesity. However, the impact of such foods on the brain has not been fully characterized. Here, we evaluated the effects of long-term consumption of a HFCS-Moderate Fat diet (HFCS-MFD) on behavior, neuronal signal transduction, gut microbiota, and serum metabolomic profile in mice to better understand how its consumption and resulting obesity and metabolic alterations relate to behavioral dysfunction. Mice fed HFCS-MFD for 16 weeks displayed enhanced anxiogenesis, increased behavioral despair, and impaired social interactions. Furthermore, the HFCS-MFD induced gut microbiota dysbiosis and lowered serum levels of serotonin and its tryptophan-based precursors. Importantly, the HFCS-MFD altered neuronal signaling in the ventral striatum including reduced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), increased expression of ΔFosB, increased Cdk5-dependent phosphorylation of DARPP-32, and reduced PKA-dependent phosphorylation of the GluR1 subunit of the AMPA receptor. These findings suggest that HFCS-MFD-induced changes in the gut microbiota and neuroactive metabolites may contribute to maladaptive alterations in ventral striatal function that underlie neurobehavioral impairment. While future studies are essential to further evaluate the interplay between these factors in obesity and metabolic syndrome-associated behavioral comorbidities, these data underscore the important role of peripheral-CNS interactions in diet-induced behavioral and brain function. This study also highlights the clinical need to address neurobehavioral comorbidities associated with obesity and metabolic syndrome.

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Background: The lactobacillus-rich microbiome forms a defense system against infections. Babies are born sterile and acquire their microbiome from exposure to the mothers' vaginal and rectal microbiota. Bacterial vaginosis (BV), which is characterized by a deficit of the Lactobacilli genera, may predispose women and their babies to an increased frequency of illness.Objective: To determine the effect of BV on HIV-infected women's post-delivery health as well as the morbidity and mortality of the exposed infant at birth, 6 months, and at 12 months of life.Study Design: A retrospective cohort study was conducted using previously collected data to investigate whether there was an association between BV-HIV-1 infected mothers and subsequent infant morbidity and mortality over a 12-month period.Methods: Data for this analysis were extracted from the original data set. Women were categorized into two groups according to whether they had a positive or negative laboratory-based diagnosis of BV using the Nugent method. The two groups were compared for socio-demographic characteristics, prior to the pregnancy experience in their current pregnancy outcome and at post-delivery morbidity, and for the duration of hospital stay. BV-exposed and unexposed infants were compared in terms of morbidity and mortality at birth, and in the periods between birth and 6 months, and between 6 and 12 months, respectively, based on prospectively collected data of the mother's past and present illness, and clinical examination at scheduled and unscheduled visits during the follow-up period of the original study. The generalized estimating equation (GEE) was used to analyze the longitudinally collected data. We used the Kaplan-Meier (KM) method to generate the cumulative hazard curve and compared the mortality in the first year of life between the two groups.Results: In total, 365 patients were included in the study. Exposure to BV was associated with an adverse maternal condition (Relative Risk [RR], 2.45; 95% confidence interval [CI], 1.04–5.81, P = 0.04) and maternal hospital admission (RR, 1.99; 95% CI, 1.14–3.48, P = 0.02) but was not linked to any neonatal morbidity at birth. There was a higher frequency of gastro-intestinal morbidity among BV-exposed infants. At 6 months, infants of BV-exposed mothers had higher odds of bloody stool (Odds Ratio [OR], 3.08; 95% CI, 1.11–10.00, P = 0.04), dehydration (OR, 2.94; 95% CI, 1.44–6.37, P = 0.01), vomiting (OR, 1.64; 95% CI, 1.06–2.56, P = 0.03), and mouth ulcers (OR, 12.8; 95% CI, 2.27–241.21, P = 0.02). At 12 months, exposure to BV was associated with dehydration (OR, 1.81; 95% CI, 1.05–3.19, P = 0.03) and vomiting (OR, 1.39; 95% CI, 1.01–1.92, P = 0.04). KM survival analysis showed non-significant higher trends of deaths among BV-exposed infants (P = 0.65).Conclusion: This study demonstrates differences in maternal and infant morbidity outcomes associated with exposure to BV. Further research is required to determine whether treatment for maternal BV mitigates maternal and infant morbidity.

BackgroundInfant morbidity is a topic of interest because it is used globally as an indicator of the status of health care in a country. A large body of evidence supports an association between bacterial vaginosis (BV) and infant morbidity. When estimating the relationship between the predictors and the estimated variable of morbidity severity, the latter exhibits imbalanced data, which means that violation of symmetry is expected. Two competing methods of analysis, that is, (1) probit and (2) logit techniques, can be considered in this context and have been applied to model such outcomes. However, these models may yield inconsistent results. While non-normal modeling approaches have been embraced in the recent past, the skewed logit model has been given little attention. In this study, we exemplify its usefulness in analyzing imbalanced longitudinal responses data.MethodologyWhile numerous non-normal methods for modeling binomial responses are well established, there is a need for comparison studies to assess their usefulness in different scenarios, especially under a longitudinal setting. This is addressed in this study. We use a dataset from Kenya about infants born to human immunodeficiency virus (HIV) positive mothers, who are also screened for BV. We aimed to investigate the effect of BV on infant morbidity across time. We derived a score for morbidity incidences depending on illnesses reported during the month of reference. By adjusting for the mother's BV status, the child's HIV status, sex, feeding status, and weight for age, we estimated the standard binary logit and skewed logit models, both using Generalized Estimating Equations.ResultsResults show that accounting for skewness in imbalanced binary data can show associations between variables in line with expectations documented by the literature. In addition, an in-depth analysis accounting for skewness has shown that, over time, maternal BV is associated with multiple health conditions in infants.InterpretationMaternal BV status was positively associated with infant morbidity incidences, which highlights the need for early intervention in cases of HIV-infected pregnant women.

Purpose. To present a rare case of brainstem anesthesia from retrobulbar block and discuss evidence-based methods for reducing the incidence of this complication. Case. A 72-year-old female, was given a retrobulbar block of 5 mL of bupivacaine 0.5% for postoperative pain management, after a globe rupture repair under general anesthesia. Prior to injection, the patient was breathing spontaneously via the anesthesia machine circuit and had not received any additional narcotics/muscle relaxants for 2.5 hr (with full recovery of neuromuscular blocking agent after anesthetic reversal). Over 7 min, however, there was a steady increase in ETCO2 and the patient became apneic, consistent with brainstem anesthesia. She remained intubated and was transported to the postanesthesia care unit for prolonged monitoring, with eventual extubation. Discussion. Brainstem anesthesia is an important complication to recognize as it can lead to apnea and death. The judicious use of anesthetic volume, shorter needle tips, and mixed formulations can help reduce the chance of brainstem anesthesia. Observation of the contralateral eye 5–10 minutes after injection for pupillary dilation, and prior to surgical draping, can help identify early CNS involvement.

Background: Necrotizing enterocolitis (NEC) has emerged as the most common neonatal gastrointestinal emergency, is the most common cause of death in neonates undergoing surgery, and accounts for yearly additional hospital charges in excess of $6.5 million. Prematurity is the only common variable identified in case-controlled studies exploring this disease. Objectives: To improve the understanding of the relationship between factors related to intestinal inflammation and ischemia and the enteral feeding regimen in the context of the premature gut, thereby identifying antecedents of NEC. Methods: Data were collected from the medical records of 247 premature infants for this retrospective case-controlled study. Diagnosis of NEC, as defined by Bell Stages IIA-IIIB, was required for study group assignment (n = 84). Multivariate analysis techniques were used to predict the relationships between selected variables on the outcome of NEC. Results: Premature infants were 13 times more likely to develop NEC if the infant required increased respiratory support to maintain oxygenation during the early neonatal period and 6.4 times more likely to develop NEC if the infant did not receive nutritionally fortified enteral feedings of breast milk. When both factors were present, the odds of NEC increased 28.6 times when compared with infants without these factors. Discussion: The study findings extend knowledge of antecedents to NEC beyond prematurity, highlighting the role that respiratory support and nutritional fortification of enteral feedings play in the pathogenesis of this disease. Early identification of antecedents to NEC will improve critical care management of the neonate and, in turn, decrease the incidence of this devastating gastrointestinal disease. The study findings will guide further inquiry in neonatal nutrition, physiologic and metabolic functioning, and acute clinical management of the neonate. [ABSTRACT FROM AUTHOR]

Many positive-sense RNA viruses transcribe subgenomic (sg) mRNAs during infections that template the translation of a subset of viral proteins. Red clover necrotic mosaic virus (RCNMV) expresses its capsid protein through the transcription of a sg mRNA from RNA1 genome segment. This transcription event is activated by an RNA structure formed by base pairing between a trans-activator (TA) in RNA2 and a trans-activator binding site (TABS) in RNA1. In this study, the impact of the structural context of the TABS in RNA1 on the TA–TABS interaction and sg mRNA transcription was investigated using in vitro and in vivo approaches. The results (i) generated RNA secondary structure models for the TA and TABS, (ii) revealed that the TABS is partially base paired with proximal upstream sequences, which limits TA access, (iii) demonstrated that the aforementioned intra-RNA1 base pairing involving the TABS modulates the TA–TABS interaction in vitro and sg mRNA levels during infections, and (iv) revealed that the TABS in RNA1 can be modified to mediate sg mRNA transcription in a TA-independent manner. These findings advance our understanding of transcriptional regulation in RCNMV and provide novel insights into the origin of the TA–TABS interaction.

Use of bibliotherapy to address childhood teasing and bullying is an innovative approach school nurses should consider as they work to promote a healthy school environment. Children's books serve as a unique conduit of exchange between parents, teachers, and children. Bibliotherapy, using books to help people solve problems, involves three stages: identification, catharsis, and insight. These stages lend themselves well to coping with the sensitivities related to teasing and bullying. Salient research findings pertinent to teasing and bullying have made their way into the children's literature and have been well received by children and their families over the course of the Child Adolescent Teasing in Schools (CATS) book review project and web site development. After exposure to a fictional story about teasing and bullying, children have shared their own nonfictional account of this often devastating experience and have come to develop successful coping strategies for dealing with the teasing and bullying that takes place in schools nationwide. [ABSTRACT FROM AUTHOR]

This paper contributes to the body of knowledge associated with the analysis of transdisciplinary research. We use a narrative centered approach, focusing on hybridity, sensemaking and the potential for transdisciplinary research to foster agency.When confronted with changes, people – as individuals – and local communities – as groups – make sense of them in the light of their own knowledge, beliefs and experiences. The process by which communities make sense of changing institutional and natural environments can be defined as the interaction between their own frame of reference and the perception of the situational demands inherent to changes, together with their interpretation of these changes. Such a dynamic process of sensemaking constantly redefines the boundaries of the narratives that community members can call on to give meaning to their past, present and future. In this paper we use five case studies to analyze how this sensemaking plays out in situations of changing climate risk and changing frames of reference associated with the presence of transdisciplinary scientists. We identify the central challenge of ambiguity. We define ambiguity as situations where narratives of change assign different meanings to the changes observed. In such situations, we observe three potential outcomes in our case studies: (1) communities appear to be forced into inaction – as a consequence of agency-depriving senselessness; (2) communities appear to be cornered into maladaptation – as a consequence of a misguided sense of agency; and (3) communities try to resolve ambiguity and effectively move forward – as knowledge-based agency-fostering exercise. In light of these results, we argue that by contributing to the clarification of such ambiguities, climate science may contribute to increases in local agency, thus enhancing adaptive capacities. We conclude by proposing that climate science be place-based and community–centered. The purpose of such a shift would be aimed at building the agency-enhancing sensemaking of local communities.

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used “additional PH signs” where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

This column describes findings and best-practice recommendations from CARE (Communicating and Relating Effectively), a prospective randomized study in which 5,169 mothers were screened for postpartum depression. The prevalence rate was 13%. Results support use of the Edinburgh Postnatal Depression Screening Scale and a diagnostic assessment for those who screen positive. Of the 674 mothers with positive screens, 26% were not asked about their emotional state by clinicians. Screening must be linked to treatment options via referral and follow-up. Best-practice strategies for implementing screening include educating clinicians and postpartum women. [ABSTRACT FROM AUTHOR]