DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance.

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.

Rural-urban differences in the perceived impact of COVID-19 on mental health by European women.

PURPOSE: Many studies have documented an adverse impact of the pandemic on women´s mental health. This cross-sectional study aims to explore associations between women's perceived impact of lockdowns and curfews on their mental health and their residential location, along with other contextual and individual factors. METHODS: Using data from the Flash Eurobarometer 2712 "Women in times of COVID-19", conducted between January 25 and February 3, 2022, across the 27 Member States of the European Union (n = 23,671), this study applied bivariate tests and stratified models based on respondent location (rural areas, small or medium-sized towns and urban areas). The exploration sought predictors influencing the perceived mental health impact, encompassing five individual characteristics (age, disability, employment status, educational attainment, and household type), perceptions of violence against women, and country of residence. The dependent variable was assessed subjectively, measured on a scale from 1 (minor negative impact) to 5 (major negative impact). RESULTS: Women living in urban areas generally reported a higher perceived negative impact on mental health compared to women in rural areas or in small/medium-sized towns. Age and disability were significantly linked to perceiving a negative impact on mental health. Similar adjusted odds ratios for age were observed across rural areas (aOR 0.97, 95% CI = 0.97-0.98), small or medium-sized towns (aOR 0.98, 95% CI = 0.97-0.98), and urban areas (aOR 0.97, 95% CI = 0.97-0.98). In terms of disability, the odds were higher in rural areas (aOR 1.44, 95% CI = 1.20-1.73) than in urban ones (aOR 1.36, 95% CI = 1.15-1.62). Among women residing in urban areas, those in childless couples were less likely to perceive a negative impact on mental health (aOR 0.89, 95% CI = 0.80-0.99) compared to women in couples with children. Respondents perceiving increased violence against women due to COVID-19 were more likely to perceive a negative impact on mental health, with higher odds ratios in rural areas (aOR 1.56, 95% CI = 1.40-1.74) compared to urban areas (aOR 1.29, 95% CI = 1.17-1.41). Differences across countries were also found. CONCLUSION: The perceived impact of lockdowns and curfews on mental health exhibited variance between urban and rural areas. These disparities were influenced by individual characteristics such as age, disability, or household type, as well as the effects of COVID-19 on violence against women and contextual variables like country of residence.

Individual, household and institutional level predictors of waste sorting: Evidence for Ecuador.

The rapid increase in waste generation in developing countries presents significant challenges, necessitating effective waste management strategies. This study examines the influence of individual, household and institutional factors on waste sorting behaviours in Ecuador, employing an ordered logistic regression model. Data were sourced from the 2019 National Multipurpose Household Survey (NMHS) and the Census of Economic Environmental Information in Decentralised Autonomous Governments (CEEIGAD). The NMHS uses a two-stage probabilistic sampling methodology, with census sectors as the primary sampling units and households as the secondary units. After excluding outliers and selecting individuals aged 15-65 years, the final sample consisted of 8601 households, including 26,175 individuals. The findings reveal that personal attributes such as gender, ethnicity, age, marital status and environmental concern significantly influence waste sorting behaviours. Household characteristics, including urban or rural location, are also critical. Institutional factors, such as municipal regulations, waste collection fees and waste separation at source, play essential roles in promoting waste separation. The study highlights the necessity for targeted governmental policies. Recommendations include improving environmental education, increasing sorting infrastructure in urban areas and ensuring waste collection systems maintain the separation of waste streams.

Transfusion-transmission of hepatitis E virus through red blood cell transfusion but not through platelet concentrates: A case report from Spain.

BACKGROUND: Few cases of transfusion-transmitted hepatitis E virus (HEV) have been published in Spain. Here, we describe a well-characterized lookback investigation of a transfusion-transmitted HEV case at the Community Centre for Blood and Tissues of Asturias (Spain). CASE REPORT: A female patient with chronic myeloid leukemia underwent an allogeneic bone marrow transplant in March 2019 and showed alterations in liver function shortly afterwards. This patient received blood components from 30 different donors in the 3 months before the transplant. Frozen plasma samples from these donations were investigated for the presence of HEV-RNA. One frequent donor was identified as asymptomatic HEV RNA-positive at the time of his whole blood donation. The investigation revealed that this donor's plasma unit, originally intended for the fractionation industry, had a viral RNA concentration of 1.9 × 104 copies/mL. HEV RNA was detected initially in the index patient who received the red cell concentrate from this donor 25 days after the transfusion. HEV RNA isolated from both donor and recipient were identified as subtype 3f. The recipient of platelet concentrate (PC), treated with a riboflavin-based pathogen reduction technology (PRT) was not infected, being negative for the presence of HEV IgM, IgG, and HEV RNA before and after the transfusion. CONCLUSION: This case study shows that HEV was transmitted through red cell transfusion to a recipient, while the patient who received riboflavin/UV light treated PC did not develop signs of infection. A causal relationship between PRT treatment of the PC and the non-transmission of HEV remains to be established.

SARS-CoV-2 surveillance strategy in essential workers of the Madrid City Council during the first epidemic wave in Spain, March-July 2020.

OBJECTIVES: To study prevalence of infection in essential workers of Madrid City Council by occupation, related characteristics, use of protective devices, risk perception, and main concerns about COVID-19 during lockdown. METHODS: A total of 30 231 workers were PCR tested for SARS-CoV-2 infection. Information was collected on COVID-19-related symptoms, risk factors, preventive equipment, and risk perception. The crude prevalence was calculated for infection, use of protective devices, perceived risk and main concerns. Additionally, adjusted prevalence and prevalence ratios (PR) were estimated for these variables using logistic regression models with age, gender, occupation, epidemiological week and laboratory as confounding factors. RESULTS: Overall prevalence of infection was 3.2% (95% CI 3.0% to 3.4%), being higher among policemen (4.4%) and bus drivers (4.2%), but lower among emergency healthcare personnel, firefighters, food market workers and burial services (<2%). Lower excess risk was observed in workers reporting occupational contact with COVID-19 cases only (PR=1.42; 95% CI 1.18 to 1.71) compared with household exposure only (PR=2.75; 95% CI 2.32 to 3.25). Infection was more frequent in symptomatic workers (PR=1.28; 95% CI 1.11 to 1.48), although 42% of detected infections were asymptomatic. Use of facial masks (78.7%) and disinfectants (86.3%) was common and associated with lower infection prevalence (PRmasks=0.68; 95% CI 0.58 to 0.79; PRdisinfectants=0.75; 95% CI 0.61 to 0.91). Over 50% of workers felt being at high risk of infection and worried about infecting others, yet only 2% considered quitting their work. CONCLUSIONS: This surveillance system allowed for detecting and isolating SARS-CoV-2 cases among essential workers, identifying characteristics related to infection and use of protective devices, and revealing specific needs for work-safety information and psychological support.

Epiretinal proliferation after rhegmatogenous retinal detachment.

PURPOSE: To determine the characteristics and appearance rate of epiretinal proliferation (ERP) on SD-OCT after surgery for rhegmatogenous retinal detachment (RRD) repair. METHODS: One hundred eight eyes of 108 patients who underwent one or more surgeries for RRD were enrolled. The eyes with other maculopathies that were directly related to RRD were excluded. Image acquisition was performed with SD-OCT (Heidelberg Engineering, Germany). Clinical charts were reviewed to assess clinical and surgical findings. Statistical analyses were performed using XLSTAT (Assinsoft, Paris, France). RESULTS: ERP was found in 9.3% eyes (n = 10). The mean initial visual acuity (logMAR) was 1.34 ± 0.82 in the ERP group compared to 0.49 ± 0.70 in the non-ERP group. PVR was present in 70.0% and chronic macular edema was found in 80.0% of eyes which developed ERP. The mean number of vitreoretinal surgeries in eyes with ERP was 3.3 ± 1.19 and only 1.44 ± 1.02 in eyes without. Silicone oil was used in 60.0% of eyes which developed ERP compared to 13.9% in the non-ERP group. CONCLUSION: ERP is a late-onset postoperative finding in eyes with RRD and can occur in absence of macular holes. Overall, ERP is more frequent in eyes with complicated courses of RRD including multiple operations, PVR, usage of silicone oil, and chronic macular edema.

Interventions in the first 1000 days to prevent childhood obesity: a systematic review and quantitative content analysis.

BACKGROUND: Childhood obesity poses a global health challenge. In recent years, there has been an increase in interventions that begin in pregnancy, putting the concept of early programming and early risk factors into practice. The present study aims to update the findings regarding interventions in the first 1000 days of life. METHODS: A systematic review based on the PRISMA guidelines was carried out in PubMed, WoS, Scopus and CINAHL to obtain the articles to be analysed. We included those studies published between 2016 and 2021. Human interventions that started within the first 1000 days of life and acted on at least one programming factor were included. Once selected, coding and quantitative content analysis was carried out to obtain a profile of the interventions during the first 1000 days. RESULTS: From all screened articles, 51 unique interventions, which met the selection criteria, were included. The majority of interventions (81%) took place in high-income areas. Almost all (86%) were targeted at the general population. The majority (54%) started in the second trimester of pregnancy. A clear majority (61%) ended at the time of birth. 44% of the interventions included all pregnant women. Only 48% of these interventions were focused on improving the nutritional status of the offspring in the short term. Most interventions collected the baby's weight at birth (68%). CONCLUSIONS: It can be concluded that current interventions are not covering as many aspects as they should. Future research should be conducted more frequently in developing countries and target disadvantaged groups. These interventions should include all pregnant women, regardless of their nutritional status, aiming to cover as many programming factors as possible and extending through the first 1000 days of life, with body mass index or skinfolds as measures of effectiveness during this period.

Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019.

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019. The study was also extended to Andorra.MethodsOf 5,197 samples received by the National Reference Laboratory during the study, 409 were HEV-RNA-positive. Among these, 294 (71.9%) were further typed based on an ORF2 sequence fragment, or, for a subset of 74, based on the full-coding genome sequence.ResultsHEV-3 was detected in 291 samples. The dominant subtype in Spain was HEV-3f (88.3%; 257/291), which occurred in all ACs, with no change in detection level over time. Within this subtype, three subclusters were characterised: HEV-3f-B, HEV-3f-A1 and HEV-3f-A2. The second most common HEV subtype was the recently described HEV-3m (7%; 21/291), with two subclusters identified: HEV-3m-A, which has been known since 2010, and HEV-3m-B, since 2014. The third most encountered subtype was HEV-3c (4.1%; 12/291), with a frequency not increasing over time, unlike observations in some European countries.ConclusionThe importance of the surveillance of HEV-3 subtype and subcluster circulation is yet to be assessed. This surveillance together with the comprehensive epidemiological characterisation of clinical cases, could support the identification of sources of transmission and the establishment of control measures nationally and internationally.

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice.

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

The Effect of Play on Pain and Anxiety in Children in the Field of Nursing: A Systematic Review.

PROBLEM: The role of play in the reduction of anxiety and pain and in the improvement of behaviours and overall wellbeing in children in the field of nursing care in hospital settings. ELIGIBILITY CRITERIA: Studies published during the period 2014-2019 including original articles in English, Spanish and Portuguese. Databases consulted: SCOPUS, MEDLINE/PubMed, WoS, and CUIDEN (Nursing database in Spanish). SAMPLE: Seventeen relevant records were selected. After critical reading using the CASPe (Critical Appraisal Skills Programme in Spanish) instrument, 7 articles were rejected and 10 were finally selected. RESULTS: Each of eight studies showed significant evidence for the role of therapeutic play in the reduction of anxiety and pain and in the overall wellbeing of paediatric patients. IMPLICATIONS: This review aimed to critically assess and synthesize the existing empirical evidence on the contributions of therapeutic play interventions for reducing anxiety, pain and improving the overall wellbeing of paediatric patients. CONCLUSIONS: Based on these findings, it may be safe to say that therapeutic play interventions are effective in reducing the negative emotional manifestations of children, decreasing preoperative anxiety and pain, improving compliance with the induction of anaesthesia and reducing anxiety and postoperative pain. There is also evidence that dramatic puppetry is an effective preoperative care and preparation strategy for reducing anxiety in children undergoing surgery.

[What not to do in the therapeutic management of bronchial asthma. Delphi consensus recommendations for physicians who treat asthma]. / Qué no se debe hacer en el manejo terapéutico del asma bronquial. Recomendaciones por consenso Delphi para los médicos que tratan el asma.

Asthma is one of the most prevalent diseases in Spain, yet despite the great diagnostic and therapeutic advances made in this field, health outcomes suggest that up to 80% of patients do not have their asthma well controlled. Although the causes of this situation are diverse, there are some practices among the professionals who treat asthma that are not conducive to improving health outcomes in this disease. Our working group has prepared this document in order to remind clinicians of a series of basic guidelines, aligned with current guidelines and recent literature, and agreed by a multidisciplinary expert panel using Delphi methodology. These recommendations about what not to do in the management of asthma in the adult patient are structured into four areas: diagnosis, monitoring, treatment and prevention of exacerbations.

Double-blind, randomized, placebo-controlled trial of allergen-specific immunotherapy with the major allergen Alt a 1.

BACKGROUND: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. OBJECTIVES: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. METHOD: We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 µg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. RESULTS: There were significant reductions in the combined symptom and medication score for the 0.37-µg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. CONCLUSION: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG4 levels.

CD45 expression discriminates waves of embryonic megakaryocytes in the mouse.

Embryonic megakaryopoiesis starts in the yolk sac on gestational day 7.5 as part of the primitive wave of hematopoiesis, and it continues in the fetal liver when this organ is colonized by hematopoietic progenitors between day 9.5 and 10.5, as the definitive hematopoiesis wave. We characterized the precise phenotype of embryo megakaryocytes in the liver at gestational day 11.5, identifying them as CD41++CD45-CD9++CD61+MPL+CD42c+ tetraploid cells that express megakaryocyte-specific transcripts and display differential traits when compared to those present in the yolk sac at the same age. In contrast to megakaryocytes from adult bone marrow, embryo megakaryocytes are CD45- until day 13.5 of gestation, as are both the megakaryocyte progenitors and megakaryocyte/erythroid-committed progenitors. At gestational day 11.5, liver and yolk sac also contain CD41+CD45+ and CD41+CD45- cells. These populations, and that of CD41++CD45-CD42c+ cells, isolated from liver, differentiate in culture into CD41++CD45-CD42c+ proplatelet-bearing megakaryocytes. Also present at this time are CD41-CD45++CD11b+ cells, which produce low numbers of CD41++CD45-CD42c+ megakaryocytes in vitro, as do fetal liver cells expressing the macrophage-specific Csf receptor-1 (Csf1r/CD115) from MaFIA transgenic mice, which give rise poorly to CD41++CD45-CD42c+ embryo megakaryocytes both in vivo and in vitro In contrast, around 30% of adult megakaryocytes (CD41++CD45++CD9++CD42c+) from C57BL/6 and MaFIA mice express CD115. We propose that differential pathways operating in the mouse embryo liver at gestational day 11.5 beget CD41++CD45-CD42c+ embryo megakaryocytes that can be produced from CD41+CD45- or from CD41+CD45+ cells, at difference from those from bone marrow.

Utility elicitation in adults and children for allergic rhinoconjunctivitis and associated health states.

PURPOSE: Allergic rhinitis and asthma symptoms are detrimental to health-related quality of life (HRQoL). Health technology appraisal agencies often require cost-utility analysis when assessing new interventions. Appropriate utility estimates, which quantify the value of different conditions in cost-utility analyses, are scarce for allergic rhinitis and asthma health states. This study aimed to generate utilities for allergic rhinitis and asthma health states from a European general population sample of adults and children. METHODS: Health state descriptions incorporating symptoms, impact of symptoms on daily life and symptom treatment were developed using clinical guidelines. Descriptions were amended with clinician and patient input, and incorporated into a survey in which each health state was followed by a standard gamble (adults) or visual analogue scale (children) item. The survey was distributed to samples of adults and children aged 8 to 11 from four European countries that were stratified to represent the general population within that country. RESULTS: 1454 adults and 1082 children completed the survey. Mean health utilities ranged from 0.635 to 0.880 and those elicited in children were lower (0.635 to 0.705) than those elicited in adults (0.812 to 0.880). Disutilities assessing the impact of increased allergic rhinitis severity and comorbidities were also greater in children than in adults. CONCLUSIONS: Symptoms of allergic rhinitis and asthma were valued as having a clinically meaningful impact on HRQoL. Children valued health states as poorer than adults, and further research should investigate whether this reflects true preferential differences or results from methodological and/or comprehension differences between the two groups.

From eHealth to iHealth: Transition to Participatory and Personalized Medicine in Mental Health.

Clinical assessment in psychiatry is commonly based on findings from brief, regularly scheduled in-person appointments. Although critically important, this approach reduces assessment to cross-sectional observations that miss essential information about disease course. The mental health provider makes all medical decisions based on this limited information. Thanks to recent technological advances such as mobile phones and other personal devices, electronic health (eHealth) data collection strategies now can provide access to real-time patient self-report data during the interval between visits. Since mobile phones are generally kept on at all times and carried everywhere, they are an ideal platform for the broad implementation of ecological momentary assessment technology. Integration of these tools into medical practice has heralded the eHealth era. Intelligent health (iHealth) further builds on and expands eHealth by adding novel built-in data analysis approaches based on (1) incorporation of new technologies into clinical practice to enhance real-time self-monitoring, (2) extension of assessment to the patient's environment including caregivers, and (3) data processing using data mining to support medical decision making and personalized medicine. This will shift mental health care from a reactive to a proactive and personalized discipline.

Organizational Learning Strategies and Verbal Memory Deficits in Bipolar Disorder.

BACKGROUND: Verbal memory (VM) impairment is prominent in bipolar disorder (BD) and is linked to functional outcomes. However, the intricacies of VM impairment have not yet been studied in a large sample of BD patients. Moreover, some have proposed VM deficits that may be mediated by organizational strategies, such as semantic or serial clustering. Thus, the exact nature of VM break-down in BD patients is not well understood, limiting remediation efforts. We investigated the intricacies of VM deficits in BD patients versus healthy controls (HCs) and examined whether verbal learning differences were mediated by use of clustering strategies. METHODS: The California Verbal Learning Test (CVLT) was administered to 113 affectively stable BD patients and 106 HCs. We compared diagnostic groups on all CVLT indices and investigated whether group differences in verbal learning were mediated by clustering strategies. RESULTS: Although BD patients showed significantly poorer attention, learning, and memory, these indices were only mildly impaired. However, BD patients evidenced poorer use of effective learning strategies and lower recall consistency, with these indices falling in the moderately impaired range. Moreover, relative reliance on semantic clustering fully mediated the relationship between diagnostic category and verbal learning, while reliance on serial clustering partially mediated this relationship. CONCLUSIONS: VM deficits in affectively stable bipolar patients were widespread but were generally mildly impaired. However, patients displayed inadequate use of organizational strategies with clear separation from HCs on semantic and serial clustering. Remediation efforts may benefit from education about mnemonic devices or "chunking" techniques to attenuate VM deficits in BD. (JINS, 2017, 23, 358-366).

Primary Langerhans Cell Histiocytosis of the Vulva: Case Report and Review of the Literature.

Langerhans cell histiocytosis (LCH) of the vulva is rare and even moreso in postmenopausal women. Twenty-six cases of primary vulvar LCH have been described in the current literature, and only 8 cases are in postmenopausal women. We report an additional case of primary vulvar LCH in a 59-yr-old woman with subsequent multiorgan involvement. In this article, we briefly describe the clinical presentation, histopathological findings, and immunohistochemistry results of vulvar LCH. We want to emphasize the importance of recognizing this entity in a woman with vulvar lesions both for the clinician and the pathologist.