Bisphenol A substitutes and obesity: a review of the epidemiology and pathophysiology.

The prevalence of obesity, a condition associated with increased health risks, has risen significantly over the past several decades. Although obesity develops from energy imbalance, its etiology involves a multitude of other factors. One of these factors are endocrine disruptors, or "obesogens", when in reference to obesity. Bisphenol A (BPA), a known endocrine disruptor used in plastic materials, has recently been described as an environmental obesogen. Although BPA-free products are becoming more common now than in the past, concerns still remain about the obesogenic properties of the compounds that replace it, namely Bisphenol S (BPS), Bisphenol F (BPF), and Bisphenol AF (BPAF). The purpose of this review is to investigate the relationship between BPA substitutes and obesity. Literature on the relationship between BPA substitutes and obesity was identified through PubMed and Google Scholar, utilizing the search terms "BPA substitutes", "bisphenol analogues", "BPS", "BPF", "BPAF", "obesity", "obesogens", "adipogenesis", "PPARγ", and "adipocyte differentiation". Various population-based studies were assessed to gain a better understanding of the epidemiology, which revealed evidence that BPA substitutes may act as obesogens at the pathophysiological level. Additional studies were assessed to explore the potential mechanisms by which these compounds act as obesogens. For BPS, these mechanisms include Peroxisome proliferator-activated receptor gamma (PPARγ) activation, potentiation of high-fat diet induced weight-gain, and stimulation of adipocyte hypertrophy and adipose depot composition. For BPF and BPAF, the evidence is more inconclusive. Given the current understanding of these compounds, there is sufficient concern about exposures. Thus, further research needs to be conducted on the relationship of BPA substitutes to obesity to inform on the potential public health measures that can be implemented to minimize exposures.

Association of Preterm Birth and Exposure to Endocrine Disrupting Chemicals.

Several studies in recent years have shown that endocrine disrupting chemicals (EDCs) can exert deleterious effects within several systems of the human body, such as the immune, neurological, and reproductive systems, among others. This review aims to summarize the investigations into the effect of EDC exposure on reproductive systems, namely preterm birth (PTB), and the efforts that international organizations have made to curb the harmful results of EDC exposure. To gather information, PubMed was initially searched for relevant articles containing the following terms: endocrine disrupting chemicals; preterm birth. PubMed was subsequently used to identify articles discussing the association between preterm birth and specific EDC exposures (BPA; phthalates; organochlorine pesticides; organophosphate pesticides; lead; PBDE; preterm birth). Both searches, limited to articles published within the past 20 years, identified several publications that have examined the association between various EDCs and PTB. While the findings of the studies differed, collectively they revealed sufficient evidence of a potential association between EDC exposure and risk of PTB. Thus, international organizations such as the United Nations Environmental Programme (UNEP) and World Health Organization (WHO) should continue to limit EDC exposure across the globe and monitor levels among individuals of reproductive age.

Leptomeningeal Carcinomatosis Mimicking Reversible Cerebral Vasoconstriction Syndrome.

Leptomeningeal carcinomatosis is the result of metastatic infiltration of the leptomeninges by malignant cells originating from an extra-meningeal primary tumor site. We describe a patient with active breast cancer who presented with thunderclap headaches (THs) and imaging showing multi-segment irregular arterial narrowing of intracranial vasculature. A 58-year-old Caucasian woman with active stage IV estrogen receptor-positive breast adenocarcinoma and migraine presented with THs. Computed tomography and brain magnetic resonance imaging (MRI) without contrast were unremarkable. Over a period of one week, she had recurrent THs. Interval vessel imaging showed multi-segment irregular arterial narrowing. Treatment with verapamil was initiated for suspected reversible cerebral vasoconstriction syndrome (RCVS). She subsequently had two discrete episodes of confusion with aphasia and left upper extremity numbness. Repeat gadolinium-enhanced MRI showed nodular leptomeningeal enhancement. Lumbar puncture revealed malignant cells in the cerebrospinal fluid consistent with leptomeningeal carcinomatosis. She subsequently underwent whole brain radiation treatment and intrathecal chemotherapy and had no further episodes of TH. Our case emphasizes the importance of considering leptomeningeal carcinomatosis in the differential diagnosis of THs and reversible cerebral vasculopathy, especially in patients with known underlying active cancer. The illustration also proves the importance of a complete work-up in patients with known malignancy in the setting of suspected RCVS.

Endocrine disrupting chemicals (EDCs) and sex steroid receptors.

Sex-steroid receptors (SSRs) are essential mediators of estrogen, progestin, and androgen signaling that are critical in vast aspects of human development and multi-organ homeostasis. Dysregulation of SSR function has been implicated in numerous pathologies including cancers, obesity, Type II diabetes mellitus, neuroendocrine disorders, cardiovascular disease, hyperlipidemia, male and female infertility, and other reproductive disorders. Endocrine disrupting chemicals (EDCs) modulate SSR function in a wide variety of cell and tissues. There exists strong experimental, clinical, and epidemiological evidence that engagement of EDCs with SSRs may disrupt endogenous hormone signaling leading to physiological abnormalities that may manifest in disease. In this chapter, we discuss the molecular mechanisms by which EDCs interact with estrogen, progestin, and androgen receptors and alter SSR functions in target cells. In addition, the pathological consequences of disruption of SSR action in reproductive and other organs by EDCs is described with an emphasis on underlying mechanisms of receptors dysfunction.

Endocrine Disrupting Chemicals, Hormone Receptors, and Acne Vulgaris: A Connecting Hypothesis.

The relationship between endocrine disrupting chemicals (EDCs) and the pathogenesis of acne vulgaris has yet to be explored in the literature. Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. The pathogenesis of acne involves several hormonal pathways, including androgens, insulin-like growth factor 1(IGF-1), estrogens, and corticosteroids. EDCs influence these pathways primarily through two mechanisms: altering endogenous hormone levels and interfering with hormone receptor function. This review article describes the mechanistic links between EDCs and the development of acne lesions. Highlighted is the contributory role of androgen receptor ligands, such as bisphenol A (BPA) and mono-2-ethylhexyl Phthalate (MEHP), via upregulation of lipogenic genes and resultant exacerbation of cholesterol synthesis. Additionally discussed is the protective role of phytoestrogen EDCs in counteracting androgen-induced sebocyte maturation through attenuation of PPARy transcriptional activity (i.e., resveratrol) and restoration of estrogen-regulated TGF-B expression in skin cells (i.e., genistein). Examination of the relationship between EDCs and acne vulgaris may inform adjunctive avenues of treatment such as limiting environmental exposures, and increasing low-glycemic, plant-rich foods in the diet. With a better understanding of the cumulative role that EDCs play in acne, clinicians can be better equipped to treat and ultimately improve the lives of their patients.

Acute Ischemic Stroke and COVID-19: Experience From a Comprehensive Stroke Center in Midwest US.

Background: COVID-19 has been associated with increased risk of venous and arterial thromboembolism including ischemic stroke. We report on patients with acute ischemic stroke and concomitant COVID-19 in a diverse patient population. Methods: This is a retrospective analysis of patients hospitalized with acute ischemic stroke (AIS) and COVID-19 to our comprehensive stroke center in Chicago, IL, between March 1, 2020, and April 30, 2020. We reviewed stroke characteristics, etiologies, and composite outcomes. We then compared our cohort with historic patients with AIS without COVID-19 admitted in the same time frame in 2019 and 2020. Results: Out of 13 patients with AIS and COVID-19, Latinos and African-Americans compromised the majority of our cohort (76.8%), with age ranging from 31-80 years. Most strokes were cortical (84.6%) and more than 50% of patients had no identifiable source, and were categorized as embolic stroke of unknown source (ESUS). A trend toward less alteplase administration was noted in the COVID-19 stroke patients compared to the non-COVID group from 2020 and 2019 (7.1 vs. 20.7% p 0.435 and 7.1 vs. 27.2% p 0.178). Endovascular thrombectomy was performed in 3 (23%) patients. Systemic thrombotic complications occurred in 3 (23%) COVID-19 AIS patients. Median National Institutes of Health Stroke Scale and modified Rankin Scale at discharge were 11 (IQR 4-23) and 4 (IQR 3-4), respectively. In the logistic regression model corrected for age and sex, COVID-19 was associated with discharge to mRS > 2 (p 0.046, OR 3.82, CI 1.02-14.3). Eight patients (63.8%) were discharged home or to acute rehabilitation, and two deceased from COVID-19 complications. Conclusion: AIS in the setting of COVID-19 is associated with worse outcomes, especially among African-American and Latino populations. Large vessel disease with ESUS was common suggesting an increased risk of coagulopathy and endothelial dysfunction as a potential etiology.

Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline.

OBJECTIVE: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. METHODS: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. RESULTS: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). CONCLUSION: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

Clinical evaluation of germline polymorphisms associated with capecitabine toxicity in breast cancer: TBCRC-015.

PURPOSE: Capecitabine is important in breast cancer treatment but causes diarrhea and hand-foot syndrome (HFS), affecting adherence and quality of life. We sought to identify pharmacogenomic predictors of capecitabine toxicity using a novel monitoring tool. METHODS: Patients with metastatic breast cancer were prospectively treated with capecitabine (2000 mg/m2/day, 14 days on/7 off). Patients completed in-person toxicity questionnaires (day 1/cycle) and automated phone-in assessments (days 8, 15). Correlation of genotypes with early and overall toxicity was the primary endpoint. RESULTS: Two hundred and fifty-nine patients were enrolled (14 institutions). Diarrhea and HFS occurred in 52% (17% grade 3) and 69% (9% grade 3), respectively. Only 29% of patients completed four cycles without dose reduction/interruption. In 39%, the highest toxicity grade was captured via phone. Three single nucleotide polymorphisms (SNPs) associated with diarrhea-DPYD*5 (odds ratio [OR] 4.9; P = 0.0005), a MTHFR missense SNP (OR 3.3; P = 0.02), and a SNP upstream of MTRR (OR 3.0; P = 0.03). GWAS elucidated a novel HFS SNP (OR 3.0; P = 0.0007) near TNFSF4 (OX40L), a gene implicated in autoimmunity including autoimmune skin diseases never before implicated in HFS. Genotype-gene expression analyses of skin tissues identified rs11158568 (associated with HFS via GWAS) with expression of CHURC1, a transcriptional activator controlling fibroblast growth factor (beta = - 0.74; P = 1.46 × 10-23), representing a previously unidentified mechanism for HFS. CONCLUSIONS: This is the first cancer pharmacogenomic study to use phone-in self-reporting, permitting augmented toxicity characterization. Three germline toxicity SNPs were replicated, and several novel SNPs/genes having strong functional relevance were discovered. If further validated, these markers could permit personalized capecitabine dosing.

Cerebral Vasculopathy and Spinal Arachnoiditis: Two Rare Complications of Ventriculitis Post Subarachnoid Hemorrhage.

This report describes a case of subarachnoid hemorrhage complicated by ventriculitis and subsequent delayed cerebral vasospasm, severe chronic spinal arachnoiditis, and Froin syndrome. A 60-year-old woman presented with diffuse aneurysmal subarachnoid hemorrhage and underwent successful coil embolization of ruptured left anterior cerebral artery aneurysm. Her course was complicated by bacterial ventriculitis and acute hydrocephalus necessitating ventriculoperitoneal shunt placement. She returned ten weeks later with recurrent headaches; CT angiography showed diffuse cerebral vasospasm. Spine magnetic resonance imaging ordered due to concern for mass or other obstruction of the cerebrospinal fluid obstruction based on lumbar puncture results showed leptomeningeal enhancement with loculated cerebrospinal fluid collections along the spinal canal concerning for spinal arachnoiditis and septal adhesions. Lumbar puncture was consistent with Froin syndrome. She was treated with calcium-channel blockers. Follow up imaging showed resolution of vasospasm, but progression of the arachnoiditis. No surgical intervention was pursued as the patient had no symptoms concerning myelopathy. Aneurysmal subarachnoid hemorrhage and ventriculitis may lead to delayed reversible vasculopathy as well as arachnoiditis, with "dry tap" and Froin-like syndrome picture. Workup should be initiated in patients who develop persistent headaches or myelopathic changes to investigate these possibilities.

The impact of caregiver health literacy on healthcare outcomes for low income minority children with asthma.

Objectives: The aim of this exploratory study was to assess the impact of caregiver health literacy (HL) on health care outcomes for their child with asthma.Methods: Caregiver dyads across two different healthcare delivery systems completed a battery of validated asthma outcome instruments, including the Newest Vital Sign™ as a measure of HL for the caregivers of children ages 7-18 y. Utilization history was obtained through the electronic medical record. Descriptive analysis with bivariate associations was conducted.Results: There was no direct relationship between HL and asthma outcomes in the 34 Hispanic and African American caregiver-child dyads. However, caregiver health literacy was significantly related to language (p = 0.02). African American English-speaking caregivers, seen in an urban emergency department, demonstrated adequate health literacy. Hispanic Spanish-speaking caregivers, seeking care in a mobile asthma van, showed limited health literacy. There was no significant association between caregivers' HL and routine asthma care visits when language and child age were controlled.Conclusions: Assessing patient factors can identify persons at risk who need additional support to negotiate the healthcare system when providing care for a child with asthma.

The large X-effect on secondary sexual characters and the genetics of variation in sex comb tooth number in Drosophila subobscura.

Genetic studies of secondary sexual traits provide insights into whether and how selection drove their divergence among populations, and these studies often focus on the fraction of variation attributable to genes on the X-chromosome. However, such studies may sometimes misinterpret the amount of variation attributable to the X-chromosome if using only simple reciprocal F1 crosses, or they may presume sexual selection has affected the observed phenotypic variation. We examined the genetics of a secondary sexual trait, male sex comb size, in Drosophila subobscura. This species bears unusually large sex combs for its species group, and therefore, this trait may be a good candidate for having been affected by natural or sexual selection. We observed significant heritable variation in number of teeth of the distal sex comb across strains. While reciprocal F1 crosses seemed to implicate a disproportionate X-chromosome effect, further examination in the F2 progeny showed that transgressive autosomal effects inflated the estimate of variation associated with the X-chromosome in the F1. Instead, the X-chromosome appears to confer the smallest contribution of all major chromosomes to the observed phenotypic variation. Further, we failed to detect effects on copulation latency or duration associated with the observed phenotypic variation. Overall, this study presents an examination of the genetics underlying segregating phenotypic variation within species and illustrates two common pitfalls associated with some past studies of the genetic basis of secondary sexual traits.

Building trust to work with children after a severe traumatic accident.

Trust is integral to nursing; yet little is known about how nurses establish trust when working with patients. This grounded theory study explored nurses' perspectives of how to build trust with a child and family in the context of paediatric acute health care. Seven paediatric acute care nurses were asked what they did when they cared for a child admitted to an acute care ward from emergency department or intensive care unit following a severe traumatic accident. Building trust emerged as the basic social process for an effective working relationship between a nurse and family to promote the rehabilitation of the child. This paper argues that building trust is critical to nurses developing a working relationship with both child and family to promote optimal health, and enables nurses to effectively step out and handover the care of the child to the family.

Building Trust to Work with Children after a Severe Traumatic Accident.

Abstract Trust is integral to nursing; yet little is known about how nurses establish trust when working with patients. This grounded theory study explored nurses' perspectives of how to build trust with a child and family in the context of paediatric acute health care. Seven paediatric acute care nurses were asked what they did when they cared for a child admitted to an acute care ward from emergency department or intensive care unit following a severe traumatic accident. Building trust emerged as the basic social process for an effective working-relationship between a nurse and family to promote the rehabilitation of the child. This paper argues that building trust is critical to nurses developing a working relationship with both child and family to promote optimal health, and enables nurses to effectively step out and handover the care of the child to the family.

Motivations to nurse: an exploration of what motivates students in Pacific Island countries to enter nursing.

The aim of this study was to explore the motivations of student nurses enrolled in nursing courses across a variety of Pacific Island countries. The image of nursing, the desire to help others, family and friends in the profession, personal experience, security, travel opportunities and flexibility have all been identified as motivators for people to enter nursing. To date, what motivates students in Pacific Island countries to enrol in a nursing course has not been investigated. An exploratory qualitative approach using focus group interviews with 152 nursing students was undertaken. Data were analysed using thematic content analysis, revealing four themes: (i) helping others; (ii) 'making a difference for my people'; (iii) following in the footsteps of others; and (iv) financial and professional gain. In a time of health and nursing workforce shortages, developing a deeper understanding of what drives people can be used to improve recruitment strategies in the future.