Transgender Care Experiences, Barriers, and Recommendations for Improvement in a Large Integrated Health Care System in the United States.

Purpose: Transgender individuals who pursue gender affirmation medical procedures often need to navigate a complex health system and interact with multiple health care providers in primary and specialty care. We sought to better understand patient, provider, and system level barriers to transgender care in a large integrated health care system in California. Methods: Three 90-min focus groups were conducted with 13 transgender individuals who received specialty care between April and August 2018 in Kaiser Permanente Southern California. Results: Participants cited common adversities such as misgendering and system-wide insensitivity during health care encounters and low levels of understanding of their transgender experience among primary care providers. Provider-patient relationship improvements were recommended for pre- and postsurgical care and service-provider sensitivity training. Suggestions include better care coordination, reducing redundancy in clearance for specialty care services, and enhancing patient support for navigation of gender affirmation services. Participants requested careful consideration when implementing systemwide routine processes such as using pronouns and names when calling patients in for visits or describing procedures on service invoices. Conclusions: Education and training programs for improving transgender care competency and enhancing care coordination between primary care and specialty care for transgender patients are warranted. Including transgender voices with lived-experience as active stakeholders in ongoing efforts such as community advisory boards to identify care gaps may facilitate patient-centered and culturally sensitive transgender care and increased patient satisfaction. Policy Implications: There is a need for systematic training for transgender care competent providers and enhancement of care coordination between primary care and specialty care.

The anticoagulation length of therapy and risk of new adverse events in venous thromboembolism (ALTERNATIVE) study: Design and survey results.

The Anticoagulation Length of Therapy and Risk of New Adverse Events In Venous Thromboembolism (ALTERNATIVE) study was designed to compare the benefits and harms of different treatment options for extended treatment of venous thromboembolism (VTE). In this paper, we describe the study cohort, survey data collection, and preliminary results. We identified 39,605 adult patients (age ≥ 18 years) from two large integrated health care delivery systems who were diagnosed with incident VTE and received initial anticoagulation therapy of 3 months or longer. A subset of the cohort (12,737) was invited to participate in a survey. Surveys were completed in English, Spanish or Mandarin via a mailed questionnaire, an online secure web link, or telephone. The survey domains included demographics, personal medical history, anticoagulant treatment history, anticoagulant treatment satisfaction, health-related quality of life and health literacy. A total of 5,017 patients participated in the survey for an overall response rate of 39.4%. The mean (SD) age of the survey respondents was 63.0 (14.5) years and self-reported race was 76.0% White/European, 11.1% Black/African American, and 3.8% Asian/Pacific Islander and 14.0% reported Hispanic ethnicity. Sixty percent of respondents completed the web survey, while 29.0% completed the mail-in paper survey, and 11.0% completed the survey via telephone. The ALTERNATIVE Study will address knowledge gaps by comparing several treatment alternatives for the extended management of VTE so that this information could be used by patients and clinicians to make more informed, patient-centered treatment choices.

Systems-level identification of key transcription factors in immune cell specification.

Transcription factors (TFs) are crucial for regulating cell differentiation during the development of the immune system. However, the key TFs for orchestrating the specification of distinct immune cells are not fully understood. Here, we integrated the transcriptomic and epigenomic measurements in 73 mouse and 61 human primary cell types, respectively, that span the immune cell differentiation pathways. We constructed the cell-type-specific transcriptional regulatory network and assessed the global importance of TFs based on the Taiji framework, which is a method we have previously developed that can infer the global impact of TFs using integrated transcriptomic and epigenetic data. Integrative analysis across cell types revealed putative driver TFs in cell lineage-specific differentiation in both mouse and human systems. We have also identified TF combinations that play important roles in specific developmental stages. Furthermore, we validated the functions of predicted novel TFs in murine CD8+ T cell differentiation and showed the importance of Elf1 and Prdm9 in the effector versus memory T cell fate specification and Kdm2b and Tet3 in promoting differentiation of CD8+ tissue resident memory (Trm) cells, validating the approach. Thus, we have developed a bioinformatic approach that provides a global picture of the regulatory mechanisms that govern cellular differentiation in the immune system and aids the discovery of novel mechanisms in cell fate decisions.

Identifying Suicidal Ideation and Attempt From Clinical Notes Within a Large Integrated Health Care System.

PURPOSE: The purpose of this study was to develop a natural language processing algorithm to identify suicidal ideation/attempt from free-text clinical notes. METHODS: Clinical notes containing prespecified keywords related to suicidal ideation/attempts from 2010 to 2018 were extracted from our organization's electronic health record system. A random sample of 864 clinical notes was selected and equally divided into 4 subsets. These subsets were reviewed and classified as 1 of the following 3 suicidal ideation/attempt categories (current, historical, and no) by experienced research chart abstractors. The first 3 data sets were used to develop the rule-based computerized algorithm sequentially and the fourth data set was used to evaluate the algorithm's performance. The validated algorithm was then applied to the entire study sample of clinical notes. RESULTS: The computerized algorithm correctly identified 23 of the 26 confirmed current suicidal ideation/attempts and all 10 confirmed historical suicidal ideation/attempts in the validation data set. It produced an 88.5% sensitivity and a 100.0% positive predictive value for current suicidal ideation/attempts, and a 100.0% sensitivity and positive predictive value for historical suicidal ideation/attempts. After applying the computerized algorithm to the entire set of study notes, we identified a total of 1,050,287 current ideation/attempt events and 293,037 historical ideation/attempt events documented in clinical notes. Those for which current ideation/attempt events were documented were more likely to be female (59.5%), 25-44 years old (28.3%), and White (43.4%). CONCLUSION: Our study demonstrated that a computerized algorithm can effectively identify suicidal ideation/attempts from clinical notes. This algorithm can be utilized in support of suicide prevention research programs and patient care quality improvement initiatives.

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

BACKGROUND & AIMS: Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. METHODS: Pre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models. RESULTS: Proteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. CONCLUSIONS: HBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

"Still on the Fence": A Mixed Methods Investigation of COVID-19 Vaccine Confidence Among Health Care Providers.

BACKGROUND: There is evidence of disparities in COVID-19 vaccine acceptance among health care providers. The purpose of this study was to examine confidence receiving and recommending COVID-19 vaccines by health care provider type and race/ethnicity. METHODS: This mixed methods study involved a cross-sectional survey and qualitative, semi-structured interviews from March to May 2021 among a sample of physicians, advanced practice providers, nurses, and pharmacists. These workers were recruited through voluntary response sampling from an integrated health system in Southern California. The primary dependent variables were (a) confidence in vaccine safety, (b) confidence in vaccine effectiveness, and (c) intent to recommend the vaccine to others. The primary independent variables were health care provider type and race/ethnicity. FINDINGS: A total of 2,948 providers completed the survey. Nurses relative to physicians were 15% less likely to perceive the COVID-19 vaccine to be safe (risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.83-0.87); 27% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.73; 95% CI = 0.69-0.76); and 11% less likely to recommend the vaccine to others (RR = 0.89; 95% CI = 0.87-0.91). Hispanic/Latinx providers were 10% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.90; 95% CI = 0.83-0.98) relative to White providers. Qualitative themes included: No need for vaccine; distrusting vaccine research and roll-out; caretaking barriers; uncertainty and potential to change one's mind; framing vaccine decisions around personal beliefs. CONCLUSIONS & APPLICATION TO PRACTICE: Health care workplaces should consider interventions to increase COVID-19 vaccination among their workers, including education and mandatory vaccination policies.

Health Care Providers' Trusted Sources for Information About COVID-19 Vaccines: Mixed Methods Study.

BACKGROUND: Information and opinions shared by health care providers can affect patient vaccination decisions, but little is known about who health care providers themselves trust for information in the context of new COVID-19 vaccines. OBJECTIVE: The purpose of this study is to investigate which sources of information about COVID-19 vaccines are trusted by health care providers and how they communicate this information to patients. METHODS: This mixed methods study involved a one-time, web-based survey of health care providers and qualitative interviews with a subset of survey respondents. Health care providers (physicians, advanced practice providers, pharmacists, nurses) were recruited from an integrated health system in Southern California using voluntary response sampling, with follow-up interviews with providers who either accepted or declined a COVID-19 vaccine. The outcome was the type of information sources that respondents reported trusting for information about COVID-19 vaccines. Bivariate tests were used to compare trusted information sources by provider type; thematic analysis was used to explore perspectives about vaccine information and communicating with patients about vaccines. RESULTS: The survey was completed by 2948 providers, of whom 91% (n=2683) responded that they had received ≥1 dose of a COVID-19 vaccine. The most frequently trusted source of COVID-19 vaccine information was government agencies (n=2513, 84.2%); the least frequently trusted source was social media (n=691, 9.5%). More physicians trusted government agencies (n=1226, 93%) than nurses (n=927, 78%) or pharmacists (n=203, 78%; P<.001), and more physicians trusted their employer (n=1115, 84%) than advanced practice providers (n=95, 67%) and nurses (n=759, 64%; P=.002). Qualitative themes (n=32 participants) about trusted sources of COVID-19 vaccine information were identified: processing new COVID-19 information in a health care work context likened to a "war zone" during the pandemic and communicating information to patients. Some providers were hesitant to recommend vaccines to pregnant people and groups they perceived to be at low risk for COVID-19. CONCLUSIONS: Physicians have stronger trust in government sources and their employers for information about COVID-19 vaccines compared with nurses, pharmacists, and advanced practice providers. Strategies such as role modeling, tailored messaging, or talking points with standard language may help providers to communicate accurate COVID-19 vaccine information to patients, and these strategies may also be used with providers with lower levels of trust in reputable information sources.

Nesfatin-1 stimulates the hypothalamus-pituitary-interrenal axis hormones in goldfish.

Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.

Project SLIP: Implementation of a PrEP Screening and Linkage Intervention in Primary Care.

Nearly a decade after becoming formally available in the U.S., HIV pre-exposure prophylaxis (PrEP) remains underutilized by populations at risk for HIV acquisition. The next generation of PrEP research is pivoting toward implementation research in order to identify the most impactful avenues for scaling up PrEP uptake. Rapid identification of patients who may be at risk for HIV in primary care settings and the ability to provide brief consultation and prescription or referral for PrEP could help to increase PrEP uptake. The current study aimed to develop and pilot-test a PrEP screening instrument that could be integrated into the workflow of busy primary care clinics to help facilitate PrEP uptake among at-risk men. During the study, PrEP screening occurred for 12 months in two primary care clinics nested within a large integrated healthcare delivery system in Southern California. An interrupted time series analysis found a significant increase in PrEP referrals overall during the screening intervention period as compared to the preceding 12 months. Findings suggest that brief HIV risk screening in primary care is acceptable, feasible, and shows preliminary effects in increasing PrEP referral rates for Black and Hispanic/Latinx men.

RESUMEN: Casi una década después de estar disponible formalmente en los EE.UU., la profilaxis previa a la exposición al VIH (PrEP) sigue siendo subutilizada por las poblaciones en riesgo de contraer VIH. La próxima generación de investigación de PrEP está girando hacia la investigación de implementación con el fin de identificar las vías de mayor impacto para ampliar el consumo de PrEP. La identificación rápida de los pacientes que pueden estar en riesgo de contraer VIH en entornos de atención primaria y la capacidad de proporcionar una consulta breve y prescripción o referencia para PrEP podría ayudar a aumentar el consumo de PrEP. El estudio actual tuvo como objetivo desarrollar y probar un instrumento de detección de PrEP que podría integrarse en el flujo de trabajo de las clínicas de atención primarias concurridas para ayudar a facilitar el consumo de PrEP entre los hombres en riesgo. Durante el estudio, la detección de PrEP se realizó durante 12 meses en dos clínicas de atención primaria ubicadas dentro de un gran sistema integrado de prestación de atención médica en el sur de California. Un análisis de series de tiempo interrumpido encontró un aumento significativo en las referencias de PrEP en general durante el periodo de intervención de detección en comparación con los 12 meses anteriores. Los hallazgos sugieren que la detección breve del riesgo de VIH en la atención primara es aceptable, factible y muestra efectos preliminares en el aumento de las tasas de referencia de PrEP para hombres negros e hispanos/latinos.

A cross-sectional survey investigating women's information sources, behaviour, expectations, knowledge and level of satisfaction on advice received about diet and supplements before and during pregnancy.

BACKGROUND: The reported long-term effects of poor maternal nutrition and uptake of recommended supplements before and during pregnancy was the impetus behind this study. Our objectives were to investigate and understand women's expectations, knowledge, behaviour and information sources used regarding the use of nutrition and vitamin supplements before and during pregnancy. METHODS: A cross-sectional survey using a self-administered questionnaire was undertaken. A purposive sampling technique was used. Women attending the antenatal clinic at Croydon University Hospital during 2015 were invited to take part in the study. The data was analysed using descriptive statistics, paired sample T-tests and Chi-squared tests, with the level of significance set at 5% (p < 0.05). RESULTS: A total of 133 pregnant women completed the survey. Analysis of the results showed that women are currently using electronic resources (33%, n = 42) rather than healthcare professionals (19%, n = 25) as an information source before pregnancy. Women who sourced information through the internet were significantly more likely to take folic acid (p = 0.006) and vitamin D (p = 0.004) before pregnancy. Women preferred to receive information from the antenatal clinic (62%, n = 83), internet (46%, n = 61) and from mobile applications (27%, n = 36). Although women believed they had sufficient knowledge (60%, n = 80) and had received adequate advice (53%, n = 70) concerning the correct supplements to take, this was not demonstrated in their behaviour, with only a small number of women (37%, n = 49) taking a folic acid supplement before pregnancy. Women mistakenly perceived the timing of supplement advice as correct, with only a small number of women (18%, n = 23) considering the advice on supplements as too late. CONCLUSIONS: Despite the small sample size, this study demonstrated that women did not receive timely and/or accurate advice to enable them to take the recommended supplements at the optimal time. Women had the misconception that they understood the correct use of pregnancy supplements. This misunderstanding may be prevented by providing women intending to become pregnant with a structured, approved electronic source of information that improves their supplements uptake.

Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate-severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.

Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8+ T cell differentiation.

COPD care delivery pathways in five European Union countries: mapping and health care professionals' perceptions.

BACKGROUND: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. OBJECTIVE: The aim of this study was to compare COPD patients' care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals' (HCPs) perceptions about the current pathways. METHODS: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. RESULTS: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. CONCLUSION: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients' engagement could optimize current care pathways resulting in a better integrated system.

Early Amiodarone-Induced Pulmonary Toxicity after Endovascular Aneurysm Repair: A Case Report.

Amiodarone is an antiarrhythmic drug that has been commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. Especially, its main metabolically active metabolite desethylamiodarone can adversely affect many organs. A very well-known severe complication of amiodarone therapy is the amiodarone-induced pulmonary toxicity. This article presents the case study of an 82-year-old male patient with acute amiodarone-induced pulmonary toxicity. The patient underwent endovascular aneurysm repair for rapidly increasing abdominal aortic aneurysm. During the postoperative period the patient developed rapid atrial fibrillation and amiodarone therapy was initiated. Subsequently, the patient went into acute respiratory failure and was requiring high supplemental oxygen support and a chest X-ray revealed bilateral pulmonary infiltrates. During the hospital course the patient required mechanical ventilator support. With discontinuation of amiodarone, supportive therapy and steroid treatment patient symptoms significantly improved. Amiodarone-induced pulmonary toxicity must be considered in the differential diagnosis of all patients on the medication with progressive or acute respiratory symptoms. Early discontinuation of amiodarone and aggressive corticosteroid therapy should be considered as a viable treatment strategy.

Pyogenic liver abscess as a warning sign for primary liver cancer: a nationwide population-based study.

BACKGROUND: There have been no large-scale population-based studies to estimate the subsequent risk of primary liver cancer (PLC) among patients with pyogenic liver abscess (PLA). This study aimed to provide relevant data. MATERIALS AND METHODS: The Taiwan Longitudinal Health Insurance Database for the years 2000 and 2005 was used. The PLA group were adult inpatients who were newly diagnosed with PLA from 2000 to 2008. The control group was randomly selected and matched with the PLA group in terms of age, sex, and date in which medical treatment was sought other than for PLA. RESULTS: There were 1,987 patients each in the PLA and control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years) from the PLA group, and 8 from the control group. After adjusting for potential covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the PLA group was significantly higher within the first year after PLA diagnosis (hazard ratio: 35.4) as compared with the control group and became insignificant (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after PLA diagnosis. CONCLUSIONS: Patients with PLA have a higher rate of PLC than matched controls, especially within the first year after the diagnosis of PLA, suggesting PLA is a warning sign for PLC.

Omega-3 fatty acid-, micronutrient-, and probiotic-enriched nutrition helps body weight stabilization in head and neck cancer cachexia.

OBJECTIVE: To evaluate whether an oral nutritional supplement enriched with omega-3 fatty acids, micronutrients, and probiotics affected body weight (BW) changes, serum albumin and prealbumin levels in patients with head and neck cancer (HNC) cachexia. STUDY DESIGN: Sixty-eight HNC patients were randomly assigned to receive either an Ethanwell/Ethanzyme (EE) regimen enriched with omega-3 fatty acids, micronutrients, and probiotics, or control (Isocal) for a 3-month period. Analysis of covariance was used to examine the association between BW change and variables. RESULTS: Patients with body mass index (BMI) <19 and those receiving the EE regimen consumed fewer daily calories but showed significantly increased BW and maintained higher serum albumin and prealbumin levels than other patients (P<.05). Their BW changes were significantly associated with changes in serum albumin and prealbumin levels. CONCLUSIONS: EE regimen improved BW as well as serum albumin and prealbumin levels in HNC patients with BMI <19.

Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish.

Nesfatin-1 is an anorexigen in goldfish. In the present study, we provide novel data indicating the presence and regulatory effects of nesfatin-1 on the hypothalamo-pituitary-ovarian (HPO) axis of goldfish. Nucleobindin-2 (NUCB2)/nesfatin-1-like immunoreactive (ir) cells are present in the hypothalamus and in the pituitary, suggesting a hypophysiotropic role for nesfatin-1. NUCB2/nesfatin-1-like ir cells colocalize gonadotropin-releasing hormone (GnRH) in the nucleus lateralis tuberis posterioris and the nucleus anterior tuberis of the goldfish hypothalamus. The presence of nesfatin-1 with GnRH in these two nuclei implicated in pituitary hormone release suggests a role for nesfatin-1 on gonadotropin secretion. A single i.p. injection of synthetic goldfish nesfatin-1 (50 ng/g body wt) resulted in an acute decrease (∼75%) in the expression of hypothalamic chicken GnRH-II and salmon GnRH mRNAs at 15 min postinjection in goldfish. Meanwhile, pituitary luteinizing hormone (LH) beta and follicle-stimulating hormone beta mRNAs were also inhibited (∼80%), but only at 60 min postinjection. Nesfatin-1 administration also resulted in a significant reduction (∼60%) in serum LH levels at 60 min postadministration. Nesfatin-1-like immunoreactivity was also found in the follicle cells, but not the oocytes, in zebrafish and goldfish ovaries. Incubation of zebrafish follicles with nesfatin-1 resulted in a significant reduction in basal germinal vesicle breakdown (∼50%) during the oocyte maturation. In addition, nesfatin-1 also attenuated the stimulatory effects of maturation-inducing hormone on germinal vesicle breakdown. Together, the current results indicate that nesfatin-1 is a metabolic hormone with an inhibitory tone on fish reproduction. Nesfatin-1 appears to elicit this suppressive effect through actions on all three tissues in the fish HPO axis.

Calcium and other signalling pathways in neuroendocrine regulation of somatotroph functions.

Relative to mammals, the neuroendocrine control of pituitary growth hormone (GH) secretion and synthesis in teleost fish involves numerous stimulatory and inhibitory regulators, many of which are delivered to the somatotrophs via direct innervation. Among teleosts, how multifactorial regulation of somatotroph functions are mediated at the level of post-receptor signalling is best characterized in goldfish. Supplemented with recent findings, this review focuses on the known intracellular signal transduction mechanisms mediating the ligand- and function-specific actions in multifactorial control of GH release and synthesis, as well as basal GH secretion, in goldfish somatotrophs. These include membrane voltage-sensitive ion channels, Na(+)/H(+) antiport, Ca(2+) signalling, multiple pharmacologically distinct intracellular Ca(2+) stores, cAMP/PKA, PKC, nitric oxide, cGMP, MEK/ERK and PI3K. Signalling pathways mediating the major neuroendocrine regulators of mammalian somatotrophs, as well as those in other major teleost study model systems are also briefly highlighted. Interestingly, unlike mammals, spontaneous action potential firings are not observed in goldfish somatotrophs in culture. Furthermore, three goldfish brain somatostatin forms directly affect pituitary GH secretion via ligand-specific actions on membrane ion channels and intracellular Ca(2+) levels, as well as exert isoform-specific action on basal and stimulated GH mRNA expression, suggesting the importance of somatostatins other than somatostatin-14.

Response to sorafenib in a patient with metastatic xp11 translocation renal cell carcinoma.

Sorafenib, a multikinase inhibitor of tumour-cell proliferation and angiogenesis, has been shown to have a role in the treatment of metastatic renal cell carcinoma (RCC). Xp11 translocation carcinoma is a rare subtype of RCC. We report an 18-year-old male patient with metastatic Xp11 translocation RCC who was responsive to sorafenib treatment. Six weeks after commencement of treatment with sorafenib, a CT scan of the patient showed increased central necrosis of the kidney mass and para-aortic lymph nodes as well as regression of the lung and pleural masses. The patient had a progression-free survival of 12 months, and overall survival of 15 months. The most severe adverse effects were grade 3 dermatitis and grade 3 anaemia. This case has demonstrated for the first time that sorafenib is active against Xp11 translocation RCC.

Fluoxetine affects weight gain and expression of feeding peptides in the female goldfish brain.

Serotonin has been implicated in the regulation of feeding and growth in vertebrates. However, the mechanisms through which serotonin mediates its anorectic effects are only partially understood. In this study we measured food intake and difference in weight gain in sexually regressed female goldfish intraperitionally injected with fluoxetine, a selective serotonin reuptake inhibitor (SSRI). The experiment was conducted in July, a period in which female goldfish show maximum body growth rates. After an acclimation period of one week, goldfish were injected every 3 d with 5 microg/g body weight fluoxetine for 13 d. Fluoxetine injections resulted in a significant decrease in food intake, as well as a significant decrease in weight gain. To investigate potential mechanisms, neuropeptide gene expression in the hypothalamus and telencephalon was determined using real-time RT-PCR. We found a 2.3-fold up-regulation of both CRF1 (p<0.03) and NPY mRNAs (p<0.04) in the hypothalamus. In the telencephalon there was a 2.3-fold decrease (p<0.02) of NPY mRNA and a 3.2-fold increase (p<0.02) in CART-1 mRNA. No changes in tachykinin mRNA were observed in either hypothalamus or telencephalon. In contrast, brain somatostatin-2 and serum GH levels were unaffected by fluoxetine. These results indicate that alteration of central serotoninergic tone reduces food intake and weight gain and increases the expression of potent inhibitory feeding neuropeptides. However, expression of the orexigenic neuropeptide NPY was increased in the hypothalamus. The results are discussed in the context of fluoxetine as a pharmaceutical of concern in the aquatic environment.