Progressive multifocal leukoencephalopathy as the presenting feature in a patient with occult low-count monoclonal B-cell lymphocytosis.

Introduction: Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL) is a relatively poorly understood entity which has been suggested to be very common in asymptomatic adults and possibly related to infectious complications despite not progressing to CLL. Methods: We describe the first case of Progressive Multifocal Leukoencephalopathy (PML) presenting in a 72-year-old man with LC-MBL but no other immunocompromising conditions. Results: A diagnosis of PML was confirmed with classic MRI findings in association with a high CSF John Cunningham polyomavirus (JCV) viral load (4.09' 105 copies/mL). An extensive search for underlying immunocompromising conditions only demonstrated LC-MBL representing approximately 4% of total leukocytes (0.2' 109/L). Discussion: This is the first report of PML in association with LC-MBL. Careful review of peripheral blood flow cytometry results is necessary to identify this disorder. Further study of the epidemiology and infectious complications of LC-MBL are warranted.

Introduction: La lymphocytose monoclonale à cellules B (LMB) est une maladie relativement mal comprise qui serait très courante chez des adultes asymptomatiques et qui pourrait être liée à des complications infectieuses, même si elle n'évolue pas en leucémie lymphocytique chronique. Méthodologies: Nous décrivons le premier cas de leucoencéphalopathie multifocale progressive (LEMP) observé chez un patient (72 ans) atteint de LMB, mais ne présentant pas d'autres pathologies induisant une immunodéficience. Résultats: Des résultats d'IRM classiques et une forte charge du virus JC (John Cunningham) dans le liquide céphalorachidien (4,09 × 105 copies/mL) ont confirmé un diagnostic de LEMP. De nombreux tests visant à révéler une immunodéficience sous-jacente ont seulement montré que les cellules B monoclonales représentaient environ 4% des leucocytes totaux (0,2 × 109/L). Discussion: Il s'agit du premier cas observé de LEMP en association avec une LMB. Il faut analyser soigneusement les résultats d'une cytométrie en flux du sang périphérique pour diagnostiquer ce trouble. Il convient de continuer d'étudier l'épidémiologie et les complications infectieuses de la LMB.

Effect of social and behavioral change interventions on minimum dietary diversity among pregnant women and associated socio-economic inequality in Rajasthan, India.

BACKGROUND: Maternal dietary diversity is a key to improving the birth and child health outcomes. Besides socio-economic factors, the nutrition specific program- Social and Behavioural Change Communication (SBCC) interventions aimed to improve maternal dietary diversity has varied levels of impact on the socio-economic groups in poor resource setups. OBJECTIVE: To measure the factors associated with the minimum dietary diversity (MDD) among pregnant women in selected districts of Rajasthan with special emphasis on the SBCC components. Additionally, it measures the socio-economic gaps in the behaviour of consumption of diversified diet during pregnancy. METHODS: Data from a cross sectional survey of 6848 pregnant women, who have received a continuous SBCC counselling and registered under a state introduced conditional cash transfer program, during May to June, 2023, in five intervention districts -Banswara, Baran, Dunagrpur, Pratapgarh and Udaipur in Rajasthan was used. A 24 h recall based food consumption behaviour has been gathered to measure the MDD of pregnant women. Study has used descriptive statistics, multivariate regressions, and multivariate decomposition analysis to address the research objectives. RESULTS: Study finds that only 55.2% of pregnant women are consuming diverse diet in the study duration with mean dietary diversity score is 4.8 (+/- 1.5). Logistic regression finds that SBCC components such as frontline workers (aOR = 1.3, CI: 1.1-1.4), community motivators (aOR = 1.9, CI: 1.7-2.1), and participation in MCHND (aOR = 1.0, CI: 0.9-1.2) have significant and higher likelihood on consumption of MDD food on previous day. A higher education and belonging from richer wealth quintile also show higher association for consumption of MDD. Multivariate decomposition shows, among richest and poorest wealth categories there is 19% point difference (58% difference due to coefficient vs. 42% difference due to composition) in MDD consumption. This is positively contributed by the caste and educational categories of women. CONCLUSION: Despite a predominant vegetarian diet consuming population, better maternal dietary diversity was observed among those exposed to higher dose of SBCC intervention package. Educational status and caste of the respondent were significantly associated with minimum dietary diversity and contributed to the socio-economic inequality highlighting the importance of tailored and sustained SBCC interventions.

Intersectionality in Medical Education: A Meta-Narrative Review.

Introduction: Despite increasing attention to improving equity, diversity, and inclusion in academic medicine, a theoretically informed perspective to advancing equity is often missing. Intersectionality is a theoretical framework that refers to the study of the dynamic nature of social categories with which an individual identifies and their unique localization within power structures. Intersectionality can be a useful lens to understand and address inequity, however, there is limited literature on intersectionality in the context of medical education. Thus, we explored how intersectionality has been conceptualized and applied in medical education. Methods: We employed a meta-narrative review, analyzing existing literature on intersectionality theory and frameworks in medical education. Three electronic databases were searched using key terms yielding 32 articles. After, title, abstract and full-text screening 14articles were included. Analysis of articles sought a meaningful synthesis on application of intersectionality theory to medical education. Results: Existing literature on intersectionality discussesthe role of identity categorization and the relationship between identity, power, and social change. There are contrasting narratives on the practical application of intersectionality to medical education, producing tensions between how intersectionality is understood as theory and how it is translated in practice. Discussion: A paucity in literature on intersectionality in medical education suggests that there is a risk intersectionality may be understood in a superficial manner and considered a synonym for diversity. Drawing explicit attention to its core tenets of reflexivity, transformational identity, and analysis of power is important to maintain fidelity to how intersectionality is understood in broader critical social science literature.

Assessment of SARS-CoV-2 Seropositivity During the First and Second Viral Waves in 2020 and 2021 Among Canadian Adults.

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented. Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults. Design, Setting, and Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada. A sample of 19 994 Canadian adults (aged ≥18 years) was recruited from established members of the Angus Reid Forum, a public polling organization. The study comprised 2 phases (phase 1 from May 1 to September 30, 2020, and phase 2 from December 1, 2020, to March 31, 2021) that generally corresponded to the first (April 1 to July 31, 2020) and second (October 1, 2020, to March 1, 2021) viral waves. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G seropositivity (using a chemiluminescence assay) by major geographic and demographic variables and correlation with COVID-19 symptom reporting. Results: Among 19 994 adults who completed the online questionnaire in phase 1, the mean (SD) age was 50.9 (15.4) years, and 10 522 participants (51.9%) were female; 2948 participants (14.5%) had self-identified racial and ethnic minority group status, and 1578 participants (8.2%) were self-identified Indigenous Canadians. Among participants in phase 1, 8967 had DBS testing. In phase 2, 14 621 adults completed online questionnaires, and 7102 of those had DBS testing. Of 19 994 adults who completed the online survey in phase 1, fewer had an educational level of some college or less (4747 individuals [33.1%]) compared with the general population in Canada (45.0%). Survey respondents were otherwise representative of the general population, including in prevalence of known risk factors associated with SARS-CoV-2 infection. The cumulative incidence of SARS-CoV-2 infection among unvaccinated adults increased from 1.9% in phase 1 to 6.5% in phase 2. The seropositivity pattern was demographically and geographically heterogeneous during phase 1 but more homogeneous by phase 2 (with a cumulative incidence ranging from 6.4% to 7.0% in most regions). The exception was the Atlantic region, in which cumulative incidence reached only 3.3% (odds ratio [OR] vs Ontario, 0.46; 95% CI, 0.21-1.02). A total of 47 of 188 adults (25.3%) reporting COVID-19 symptoms during phase 2 were seropositive, and the OR of seropositivity for COVID-19 symptoms was 6.15 (95% CI, 2.02-18.69). In phase 2, 94 of 444 seropositive adults (22.2%) reported having no symptoms. Of 134 seropositive adults in phase 1 who were retested in phase 2, 111 individuals (81.8%) remained seropositive. Participants who had a history of diabetes (OR, 0.58; 95% CI, 0.38-0.90) had lower odds of having detectable antibodies in phase 2. Conclusions and Relevance: The Action to Beat Coronavirus study found that the incidence of SARS-CoV-2 infection in Canada was modest until March 2021, and this incidence was lower than the levels of population immunity required to substantially reduce transmission of the virus. Ongoing vaccination efforts remain central to reducing viral transmission and mortality. Assessment of future infection-induced and vaccine-induced immunity is practicable through the use of serial online surveys and participant-collected DBS.

Translation and Validation of Tamil Version of Singing Voice Handicap Index-10 (TSVHI-10).

AIM: To translate and validate the singing voice handicap index (SVHI-10) for the Tamil speaking Indian population and to evaluate the psychometric properties of the Tamil version SVHI-10 (TSVHI-10) in classically trained Carnatic singers. METHOD: Following standard translation, a total of 120 classically trained Carnatic singers: 83 singers without voice complaint and 37 singers with voice complaints answered the Tamil translation of the SVHI-10. RESULTS: The TSVHI -10 scores obatined from classically trained Carnatic singers with and singers without voice complaints were analyzed. SVHI-10 has excellent internal consistency and test retest reliability. Singers without/with voice complaint scored 7.08/22.86 total scores and for each domain Emotional (E): 1.73/5.32, Functional (F): 2.11/7.08, and Physical (P): 3.3/10.35 respectively. CONCLUSION: The TSVHI-10 questionnaire seems to be psychometrically sound and is a valuable instrument for the self-evaluation of handicaps related to voice problems in the context of singing and for making subsequent clinical decisions. The Tamil version of the SVHI-10 was successfully validated as an instrument with proper internal consistency and reliability.

The Voice-Related Quality Of Life: A Study on the Reliability and Validity of the Tamil Version.

OBJECTIVE: Voice serves as an identity and is one of the primary requisites of an individual, especially for singers who are extensive professional voice users with greater vulnerability to voice disorders. The aim of this study is to translate and validate the Tamil version of Voice-Related Quality of Life (T-VRQOL), a self-rating questionnaire that estimates the influence of voice disorders on quality of life. The study also intends to compare the T-VRQOL scores in singers (with and without voice complaint) and non-singers, and to correlate T-VRQOL and the Tamil Singing Voice Handicap Index-10 (TSVHI-10). METHOD: In this cross-sectional study, 120 native Tamil speakers (40 classically trained Carnatic singers without voice complaints, 40 Carnatic singers with voice complaints and 40 normal non-singers) in the age range of 20 to 50 years, filled in the T-VRQOL and the TSVHI-10 rating scales, along with a demographic questionnaire. RESULTS: Reliability of T-VRQOL was established with Cronbach α coefficient (r = 0.9, P < .001) and good test-retest reliability (r = 0.98). The validity of T-VRQOL was confirmed by examining convergent and discriminant validity. T-VRQOL also demonstrated a good correlation with the TSVHI-10 (r = 0.838, P < .001). On comparing the T-VRQOL scores across the groups, singers (13.88 and 24.3) obtained higher values than the non-singers (11.63). Among the singers, those with voice complaints (24.3) scored higher than those without voice complaints (13.88) in the T-VRQOL. CONCLUSIONS: The Tamil version of Voice-Related Quality of Life (VRQOL) questionnaire correlates well with TSVHI-10. It proves to be an effective clinical tool in effectively evaluating the VRQOL among the Tamil-speaking population.

Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain).

INTRODUCTION: Chronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain. METHODS AND ANALYSIS: The primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18-59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study. ETHICS AND DISSEMINATION: Ethics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: NCT03315533.

Ras Signaling Is a Key Determinant for Metastatic Dissemination and Poor Survival of Luminal Breast Cancer Patients.

Breast cancer is associated with alterations in a number of growth factor and hormone-regulated signaling pathways. Mouse models of metastatic breast cancer typically feature mutated oncoproteins that activate PI3K, Stat3, and Ras signaling, but the individual and combined roles of these pathways in breast cancer progression are poorly understood. In this study, we examined the relationship between oncogenic pathway activation and breast cancer subtype by analyzing mouse mammary tumor formation in which each pathway was activated singly or pairwise. All three oncogenes showed cooperation during primary tumor formation, but efficient dissemination was only dependent on Ras. In addition, transcriptional profiling demonstrated that Ras induced adenocarcinomas with molecular characteristics related to human basal-like and HER2(+) tumors. In contrast, Ras combined with PIK3CA(H1047R), an oncogenic mutant linked to ERα(+)/luminal breast cancer in humans, induced metastatic luminal B-like tumors. Consistent with these data, elevated Ras signaling was associated with basal-like and HER2(+) subtype tumors in humans and showed a statistically significant negative association with estrogen receptor (ER) signaling across all breast cancer. Despite this, there are luminal tumors with elevated Ras signaling. Importantly, when considered as a continuous variable, Ras pathway activation was strongly linked to reduced survival of patients with ERα(+) disease independent of PI3K or Stat3 activation. Therefore, our studies suggest that Ras activation is a key determinant for dissemination and poor prognosis of ERα(+)/luminal breast cancer in humans, and hormone therapy supplemented with Ras-targeting agents may be beneficial for treating this aggressive subtype.