Recurrent vulvovaginal candidiasis: a dynamic interkingdom biofilm disease of candida and lactobacillus

Despite the strikingly high worldwide prevalence of vulvovaginal candidiasis (VVC), treatment options for recurrent VVC (RVVC) remain limited, with many women experiencing failed clinical treatment with frontline azoles. Further, the cause of onset and recurrence of disease is largely unknown, with few studies identifying potential mechanisms of treatment failure. This study aimed to assess a panel of clinical samples from healthy women and those with RVVC to investigate the influence of Candida, the vaginal microbiome, and how their interaction influences disease pathology. 16S rRNA sequencing characterized disease by a reduction in specific health-associated Lactobacillus species, such as Lactobacillus crispatus, coupled with an increase in Lactobacillus iners. In vitro analysis showed that Candida albicans clinical isolates are capable of heterogeneous biofilm formation, and we found the presence of hyphae and C. albicans aggregates in vaginal lavage fluid. Additionally, the ability of Lactobacillus to inhibit C. albicans biofilm formation and biofilm-related gene expression was demonstrated. Using RNA sequencing technology, we were able to identify a possible mechanism by which L. crispatus may contribute to re-establishing a healthy vaginal environment through amino acid acquisition from C. albicans. This study highlights the potential formation and impact of Candida biofilms in RVVC. Additionally, it suggests that RVVC is not entirely due to an arbitrary switch in C. albicans from commensal to pathogen and that understanding interactions between this yeast and vaginal Lactobacillus species may be crucial to elucidating the cause of RVVC and developing appropriate therapies

Public perspective on potential treatment intervention harm in clinical trials-terminology and communication

Peer reviewe

The Communicability of Graphical Alternatives to Tabular Displays of Statistical Simulation Studies

Simulation studies are often used to assess the frequency properties and optimality of statistical methods. They are typically reported in tables, which may contain hundreds of figures to be contrasted over multiple dimensions. To assess the degree to which these tables are fit for purpose, we performed a randomised cross-over experiment in which statisticians were asked to extract information from (i) such a table sourced from the literature and (ii) a graphical adaptation designed by the authors, and were timed and assessed for accuracy. We developed hierarchical models accounting for differences between individuals of different experience levels (under- and post-graduate), within experience levels, and between different table-graph pairs. In our experiment, information could be extracted quicker and, for less experienced participants, more accurately from graphical presentations than tabular displays. We also performed a literature review to assess the prevalence of hard-to-interpret design features in tables of simulation studies in three popular statistics journals, finding that many are presented innumerately. We recommend simulation studies be presented in graphical form

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death

Funder: The Sidharth Burman endowmentEnd-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte–endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets

Middle East, North Africa, South Asia Initiative Report

The Middle East, North Africa, South Asia (MENASA) Initiative was created to address a lack of resources and services to support the MENASA student population at Portland State University (PSU). Formed by a group of undergraduate and graduate MENASA students, and supported administratively by the Cultural Resource Centers, the MENASA Initiative is a student-centered effort with the goal of creating a MENASA Student Center to match the other five Cultural Resource Centers (La Casa Latina Student Center, the Multicultural Student Center, the Native American Student and Community Center, the Pacific Islander, Asian, and Asian American Student Center, and the Pan-African Commons)

Gathering Space: Building Community

The Cultural Resource Centers (CRCs) at Portland State University (PSU) create a student-centered inclusive environment that enriches the university experience. The CRCs value diversity, social justice, cultural traditions, student identities, success and leadership. On November 2, 2016, PSU held a grand opening celebrating the expansion of the CRCs with the addition of two new centers, the Pan-African Commons (PAC) and the Pacific Islander, Asian, and Asian American Student Center (PIAAA). The growth of the CRCs marks a milestone in PSU’s commitment to social justice and equity. The Gathering Space, Building Community Report not only documents this growth, but also aims to highlight the depth and breadth of the influence of cultural centers on our campus. Our activities extend well beyond creating space for studying or relaxing. We impact all aspects of retention, persistence, and graduation for our students; create meaningful community connections; and foster authentic environments for coalition building

Attitudes and beliefs regarding complementary and alternative medicine in a diverse gynecologic oncology patient population

Objectives: To measure prevalence of complementary and alternative medicine (CAM) use in a diverse gynecologic oncology patient population and evaluate how attitudes and beliefs regarding CAM relate to demographic factors. Methods: A validated Attitudes and Beliefs about Complementary and Alternative Medicine (ABCAM) survey was distributed to patients with gynecologic malignancy. Results were evaluated using Pearson's Chi-squared and Fisher's exact tests for categorical variables and Wilcoxon ranks sum and Kruskal-Wallace tests for non-normally distributed variables. Results: One-hundred thirty patients completed the ABCAM survey. Self-reported race and ethnicity included Asian or Pacific Islander (n = 54; 42%), Hispanic/Latino (n = 23; 18%), White (n = 21; 16%), Black or African American (n = 20; 15%), American Indian/Alaska Native (n = 8; 6.2%) and Other (n = 4; 3.1%). Twenty-four respondents (18%) reported use of CAM. There was a significant difference in expected benefits to CAM between respondents of different ethnicities (p < 0.001). Black and Asian respondents reported greater expected benefit to CAM. Hispanic/Latino, American Indian/Alaskan Native, and White respondents reported fewer expected benefits. A significant association was found between perceived barriers to CAM and ethnicity (p 0.043), with Asian, Hispanic/Latino and White respondents perceiving more barriers while Black and American Indian/Alaskan Natives reported perceiving fewer barriers to CAM. Respondents with incomes greater than $100,000 reported fewer barriers to CAM. Conclusions: Use of CAM among gynecologic oncology patients is lower than previously thought. Income, race, and ethnicity inform patient engagement with CAM and can be used to better tailor the provision of evidence-based CAM interventions to benefit a greater number of gynecologic cancer patients

Management of SIADH-related hyponatremia due to psychotropic medications - An expert consensus from the Association of Medicine and Psychiatry.

OBJECTIVE: Hyponatremia is the most common electrolyte imbalance encountered in clinical practice and is associated with negative healthcare outcomes and cost. SIADH is thought to account for one third of all hyponatremia cases and is typically an insidious process. Psychotropic medications are commonly implicated in the etiology of drug induced SIADH. There is limited guidance for clinicians on management of psychotropic-induced SIADH. METHODS: After an extensive review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus recommendations for management of psychotropic-induced SIADH. A risk score was proposed based on risk factors for SIADH to guide clinical decision-making. RESULTS: SSRIs, SNRIs, antipsychotics, carbamazepine, and oxcarbazepine have moderate to high level of evidence demonstrating their association with SIADH. Evaluation for an avoidance of medications that cause hyponatremia is particularly important. Substitution with medication that is less likely to cause SIADH should be considered when appropriate. We propose an algorithmic approach to monitoring hyponatremia with SIADH and corresponding treatment depending on symptom severity. CONCLUSIONS: The proposed algorithm can help clinicians in determining whether psychotropic medication should be stopped, reduced or substituted where SIADH is suspected with recommendations for sodium (Na+) monitoring. These recommendations preserve a role for clinical judgment in the management of hyponatremia with consideration of the risks and benefits, which may be particularly relevant for complex patients that present with medical and psychiatric comorbidities. Further studies are needed to determine whether baseline and serial Na+ monitoring reduces morbidity and mortality

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies