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The current study investigated whether hope and its two components (agency and pathways) acted as protective factors by weakening the relations between perceived burdensomeness, thwarted belongingness, and acquired capability for suicide and suicide risk among older adults. A community sample of 594 older Australians aged from 60 to 95 years (Mage = 68.72, SDage = 6.67) completed the Suicidal Behaviors Questionnaire-Revised, Interpersonal Needs Questionnaire-Revised, Acquired Capability for Suicide Scale-Fearlessness about Death Scale, Adult Hope Scale, and Geriatric Depression Scale-short form. After controlling for depressive symptoms and sociodemographic variables, hope and agency moderated the thwarted belongingness-suicide risk relation, and hope, agency, and pathways moderated the acquired capability for suicide-risk relation. Hope may play an important role in reducing suicide risk among older adults experiencing thwarted belongingness and who have acquired the capability for suicide. Research is required to identify ways of reducing suicide risk among older adults who experience perceived burdensomeness. Increasing hope may reduce suicide risk among older adults experiencing thwarted belongingness and who have acquired the capability for suicide. [ABSTRACT FROM AUTHOR]

Recent studies have shown that there are some advantages to forecasting mortality with indicators other than age-specific death rates. The mean, median, and modal ages at death can be directly estimated from the age-at-death distribution, as can information on lifespan variation. The modal age at death has been increasing linearly since the second half of the twentieth century, providing a strong basis from which to extrapolate past trends. The aim of this paper is to develop a forecasting model that is based on the regularity of the modal age at death and that can also account for changes in lifespan variation. We forecast mortality at ages 40 and above in 10 West European countries. The model we introduce increases forecast accuracy compared with other forecasting models and provides consistent trends in life expectancy and lifespan variation at age 40 over time. [ABSTRACT FROM AUTHOR]

Background A combined deep-penetrating tumour redefined as WNT-activated deep-penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses. Objectives To review the clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms. Methods The study included 51 patients with combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available) and histological characteristics were reviewed. Immunohistochemistry for β-catenin, LEF1, HMB45, Ki67, p16 and PRAME (preferentially expressed antigen in melanoma) was performed. Atypical forms underwent next-generation sequencing (NGS) panel analysis, including driver genes implicated in DPMs, TERT -promoter (p) mutations and the investigation of the 9p21 locus via fluorescence in situ hybridization. Results Among the 51 patients (32 females and 19 males, age range 4–74 years), 68% with available clinical data (15/22) were initially suspected of having melanoma. Except for one patient, complete excision resulted in no recurrences or metastases. One patient who had an incompletely excised combined DPM developed a lymph node melanoma metastasis 10 years later. In the 51 patients, 10 samples (20%) showed atypical histological features; 7 (14%) exhibited a significant loss of p16 expression; and 2 (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in 11 patients revealed a double mutation BRAF V600E and exon 3 CTNNB1 ; no TERT p mutations were detected. Conclusions Clinical suspicion of melanoma is common in combined DPMs, but malignant progression is infrequent in tumours lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumours or melanocytomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Prediction equations allow small farmers who do not have a scale to estimate the live weight of animals from their body measurements. The aim of this study was to describe the morphology and estimate the live weight from body measurements of Socorro Island Merino lambs. A group of Socorro Island Merino lambs was recorded from birth to year for live weight, rump width, rump length, withers height, body length, cannon bone perimeter, and chest girth, width, and depth. Sex and crossbreeding with hair breeds affected weight and mainly thoracic morphology at birth and at the year of Socorro Island Merino lambs, with the greatest and smaller weights and body measurements being observed in crossbreed males and purebred females, respectively. The highly significant and positive correlation between LW and CG suggests that this variable can be used as the sole predictor in exponential and linear models and in combination with other measurements in multiple linear models to provide a good estimate of LW. Chest measurements could be used as an indirect selection criterion to improve growth traits in this breed. The aim of this study was to describe the morphology and estimate live weight from body measurements of Socorro Island Merino lambs. A group of Socorro Island Merino lambs was recorded from birth to year for live weight, rump width, rump length, withers height, body length, cannon bone perimeter, and chest girth, width, and depth. The effect of the lamb type on body measurements and live weight was analyzed using ANOVA, Pearson's correlation analysis was performed to estimate the relationship between body measurements and live weight, multiple linear regressions were fitted to obtain prediction equations of live weight from the body measurements and finally, chest girth was used to generate prediction equations using linear and exponential models. At birth and at year, differences were observed in body measurements, especially those related to the thoracic region, with crossbred males showing the highest values. Live weight was correlated with almost all the body measurements, with the highest coefficients observed with chest girth, chest width, and chest depth. Live weight can be accurately predicted from multiple regression equations using several body measurements, but using only chest girth (CG) as a predictor, the exponential equation W0–365 = 0.9142 exp(0.0462 CG) showed the best accuracy. [ABSTRACT FROM AUTHOR]

Background: University students are four times more likely to experience elevated levels of psychological distress compared to their peers. The psychosocial needs of university students are associated with high psychological distress, stressful life events, and academic performance. Our study focuses on developing a measure to help universities identify these psychosocial needs. Aims: The study aimed to develop and validate the factor structure of the University Needs Instrument and identify the relationship between psychosocial needs, psychological distress and academic performance among university students. Sample: Undergraduate university students (N = 511) currently studying at university. Method: Participants completed demographic questions, the University Needs Instrument and the Kessler‐10 Psychological Distress scale. The University Needs Instrument comprises 30 items within six psychosocial factors (academic support, financial support, support from family, support from friends, practical support and emotional support), each consisting of five items. Results: Confirmatory factor analysis showed that all items significantly loaded on the six hypothesized factors. The hypothesized model was supported by the data displaying excellent model fit and psychometric properties. Our analysis determined that the UNI has strong internal consistency. The results also confirmed that university students' high levels of psychological distress and their academic performance may be affected by their psychosocial needs. Conclusions: Our findings have provided an initial validation of the UNI to help screen and identify the psychosocial needs of university students. This scale can be used to identify the appropriate psychosocial support that can be offered to students and in turn could help reduce their psychological distress, improve their psychosocial well‐being and increase academic performance. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment. Material and methods: Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed. Results: Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment. Conclusions: Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment. Clinical relevance: Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines. [ABSTRACT FROM AUTHOR]

Objective: Polyculturalism, a relatively new intergroup ideology conceptualises culture as dynamic by emphasising intergroup connections. Previous research has linked polyculturalism to less negative attitudes towards different racial and ethnic groups. However, the underpinnings of this relationship is not well understood. It was predicted that openness to experience, agreeableness, and cognitive flexibility (alternative and control) would be associated with lower racial and ethnic prejudice and that polyculturalism would mediate these relationships. Method: The sample consisted of 391 undergraduate students and community members who completed a polyculturalism measure, openness to experience and agreeableness scales of the Big Five Aspect Scale, the Cognitive Flexibility Inventory, and the Australian Racism, Acceptance, and Culture-Ethnocentrism Scale. Results: Path analysis indicated openness to experience, agreeableness, and cognitive flexibility (alternative) were each associated with less generalised racial and ethnic prejudice, and that polyculturalism mediated the relationship between openness to experience and prejudice and cognitive flexibility- alternative and prejudice. Conclusion: Polyculturalism may be an important avenue for understanding and reducing racial and ethnic prejudice in a racially and ethnically diverse Australia. Key Points What is already known about this topic: The traits of openness to experience and agreeableness, and cognitive flexibility are associated with less negative racial and ethnic attitudes. Polyculturalism is a lay diversity ideology where culture is viewed as a dynamic and evolving system that does not provide the basis for differentiating between groups. Instead of focusing on differences between cultural groups, connections between groups through interactions are emphasised. Polyculturalism is associated with less negative attitudes towards different racial and ethnic groups among other pro-diversity attitudes. What this topic adds: This study adds to the limited research into the role of lay diversity ideologies in explaining the relationship between personality and intergroup attitudes. Openness to experience, agreeableness, and cognitive flexibility (alternative) were each associated with less generalised racial and ethnic prejudice. Polyculturalism mediated the relationship between openness to experience and racial and ethnic prejudice, and the relationship between cognitive flexibility (alternative) and racial and ethnic prejudice. The Racism Acceptance and Cultural-Ethnocentrism Scale (RACES) is a psychometrically sound measure developed for the Australian context. It is a suitable tool for measuring the effectiveness of interventions for promoting more positive intergroup attitudes. [ABSTRACT FROM AUTHOR]

Depressive symptoms are a significant health concern among sexual minority women, with bisexual women at a higher risk than lesbian women. Internalized heterosexism is a key risk factor for depression among sexual minority women. Sense of belonging to the LGBTIQ + community is protective for lesbian women, but the limited research among bisexual women has shown inconsistent results. The current study investigated whether a sense of belonging to the LGBTIQ + community was directly related to fewer depressive symptoms and indirectly related via lower levels of internalized heterosexism, and whether the indirect effect was similar for bisexual and lesbian women. A sample of 175 self-identified bisexual women and 311 self-identified lesbian women aged 18 to 61 years (M = 31.91, SD = 11.38) completed the Psychological subscale of the Sense of Belonging Instrument, the Internalized Homophobia Scale, and the Center for Epidemiologic Studies Depression Scale. Bisexual women reported higher levels of depressive symptoms and internalized heterosexism, and lower levels of a sense of belonging to the LGBTIQ + community, than lesbian women. A sense of belonging to the LGBTIQ + community was directly associated with lower depressive symptoms and indirectly related via lower internalized heterosexism. However, sexual orientation moderated the indirect relationship. The indirect effect of a sense of belonging to the LGBTIQ + community on depressive symptoms was significant for lesbian women but not bisexual women. Results imply that increasing a sense of belonging to the LGBTIQ + community may be beneficial for bisexual and lesbian women, but the pathways by which protection is afforded will differ. [ABSTRACT FROM AUTHOR]

The main objective was to psychometrically establish the nature of the construct underlying the symptoms of anxiety and depression associated with isolation by COVID-19 in adult women of Azogues. A quantitative, non-experimental, prospective and descriptive-correlational study was carried out with a correlational, comparative and predictive crosssectional design. A simple random sampling was carried out. The sample consisted of 381 adult women (18 to 65 years old) from the city of Azogues, Ecuador. A sociodemographic survey was administered, as well as the State-Trait Anxiety Inventory (STAI) and the State-Trait Depression Inventory (IDER). A descriptive analysis was performed by means of (percentages, frequencies, central tendency measures), a normality test by means of Shapiro Wilk (W), correlation analysis (r Pearson), mean difference analysis (Student t test for independent samples) and finally a multiple linear regression. The first model for predicting anxiety and depression was statistically significant for age (f= 12.66; p= .0001). Anxiety was not a statistically significant predictor for age (β= -0.04; p= .562). While depression was a statistically significant inverse or negative predictor of age (β= -0.27; p= .002). and for the second model of prediction of anxiety and depression was statistically significant for the days of quarantine (f= 4.61; p= .0001). Anxiety was a negative predictor of quarantine days (β= -0.16; p= .002) and depression a positive predictor of quarantine days (β= 0.25; p= .001). [ABSTRACT FROM AUTHOR]

Depression is a significant mental health issue for bisexual women. While theory and research indicates that sense of belonging is important for mental health, limited research has investigated this in relation to bisexual women belonging to the LGBTQ + community. Existing research indicates that identification and involvement with the LGBTQ + community is not protective for the mental health of bisexual women. The protective nature of the extent to which bisexual women feel valued and needed within the lesbian community has not been examined. The current study examined the relationships between sense of belonging to the lesbian and heterosexual communities and depressive symptoms among bisexual women. A sample of 306 Australian self-identified bisexual women completed the Center for Epidemiologic Studies Depression Scale and the psychological subscale of the Sense of Belonging Instrument. Results indicated that sense of belonging to each community was related to lower levels of depressive symptoms. Further, levels of belonging to each community interacted, indicating that sense of belonging to the lesbian community was protective for bisexual women with lower, but not higher, levels of sense of belonging to the heterosexual community. Results imply that increasing belonging to the lesbian community is important for bisexual women who do not feel they belong in the heterosexual community. The challenge is how to increase sense of belonging of bisexual women in the lesbian community, where they are exposed to negative attitudes about their sexuality. [ABSTRACT FROM AUTHOR]

Background: Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact. Aim: We assessed the accuracy of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses. Methods: One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification. Results: Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 [70%] major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 0–37), 18% (95% CI: 2–52) for invasive fungal infections, 25% (95% CI: 5–57) for bacterial sepsis, 34% (95% CI: 16–57), for tuberculosis, and 46% (95% CI: 19–75) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 [66%] vs. 17/39 [44%]; p = 0.0236). Conclusions: Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine whether the presence of the interjection 'um' can distinguish between the deceptive and truthful speech of individuals who are practised in the art of impression management. A total of 50 truthful and 61 deceptive statements were extracted from the speech of celebrities participating in a televised comedy panel show where celebrity guests try to convince an opposing team of their truthfulness. Participants' use of 'um' (measured as a percentage of the total word count of each statement) was analysed. The results show that, on average, 'um' was used almost three times as often in the speakers' true statements compared to their false ones. A discriminant analysis revealed that the presence of 'um' is more effective than human judgement alone in determining veracity. These findings suggest that the presence of the filler 'um' in speech is useful in the identification of true versus false oral statements. [ABSTRACT FROM AUTHOR]

Background: Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed.Methods and Findings: In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction.Conclusions: The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented. [ABSTRACT FROM AUTHOR]

Background: In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting.Methods and Findings: In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive and negative predictive values of the MIA diagnoses were calculated. A CoD was identified in all cases in the CDA and in 52/54 (96%) of the cases in the MIA, with infections and malignant tumors accounting for the majority of diagnoses. The MIA categorization of disease showed a substantial concordance with the CDA categorization (Kappa = 0.70, 95% CI 0.49-0.92), and sensitivity, specificity, and overall accuracy were high. The ICD-10 diagnoses were coincident in up to 75% (36/48) of the cases. The MIA allowed the identification of the specific pathogen deemed responsible for the death in two-thirds (21/32; 66%) of all deaths of infectious origin. Discrepancies between the MIA and the CDA in individual diagnoses could be minimized with the addition of some basic clinical information such as those ascertainable through a verbal autopsy or clinical record. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.Conclusions: The MIA showed substantial concordance with CDA for CoD identification in this series of pediatric deaths in Mozambique. This minimally invasive approach, simpler and more readily acceptable than the more invasive CDA, could provide robust data for CoD surveillance, especially in resource-limited settings, which could be helpful for guiding child survival strategies in the future. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique.Methods and Findings: In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.Conclusions: A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality. [ABSTRACT FROM AUTHOR]

Clara Menéndez and colleagues consider the importance of conducting autopsies and possible alternative methods for determining cause of death in resource-limited settings. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 79-year-old woman with unexplained progressive cholestasis admitted to the hospital suffering from jaundice and abdominal pain. Topics include constitutional symptoms, and pruritus where the patient seen in dermatology because of pruriginous skin lesions; and physical examination revealing multiple presternal yellowish papules on an erythematous base coalescing into a V‑shaped plaque.

Background and Aims: Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings. Methods: A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles. Results: The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs. Conclusions: A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries. [ABSTRACT FROM AUTHOR]

Aims Experience in the use of whole slide imaging (WSI) for primary diagnosis in pathology is very limited. We aimed to determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of routine gynaecological biopsies. Methods All gynaecological specimens (n=452) received over a 2-month period at the Department of Pathology of the Hospital Clinic of Barcelona were analysed blindly by two gynaecological pathologists, one using CLM and the other WSI. All slides were digitised in a Ventana iScan HT (Roche diagnostics) at 200x. All discrepant diagnoses were reviewed, and a final consensus diagnosis was established. The results were evaluated by weighted κ statistics for two observers. Results The level of interobserver agreement between WSI and CLM evaluations was almost perfect (κ value: 0.914; 95% CI 0.879 to 0.949) and increased during the study period: ?? value 0.890; 95% CI 0.835 to 0.945 in the first period and 0.941; 95%; CI 0.899 to 0.983 in the second period. Major discrepancies (differences in clinical management or prognosis) were observed in 9 cases (2.0%). All discrepancies consisted of small lesions (8 high grade squamous intraepithelial lesions of the uterine cervix, one lymph node micrometastasis of an ovarian carcinoma) underdiagnosed or missed in the WSI or the CLM evaluation. Discrepancies with no or minor clinical relevance were identified in 3.8% of the biopsies. No discrepancy was related to the poor quality of the WSI image. Conclusions Diagnosis of gynaecological specimens by WSI is accurate and may be introduced into routine diagnosis. [ABSTRACT FROM AUTHOR]

Melanoma develops as a result of several genetic alterations, with UV radiation often acting as a mutagenic risk factor. Deep knowledge of the molecular signaling pathways of different types of melanoma allows better characterization and provides tools for the development of therapies based on the intervention of signals promoted by these cascades. The latest World Health Organization classification acknowledged the specific genetic drivers leading to melanoma and classifies melanocytic lesions into nine distinct categories according to the associate cumulative sun damage (CSD), which correlates with the molecular alterations of tumors. The largest groups are melanomas associated with low-CSD or superficial spreading melanomas, characterized by frequent presentation of the BRAFV600 mutation. High-CSD melanomas include lentigo maligna type and desmoplastic melanomas, which often have a high mutation burden and can harbor NRAS, BRAFnon-V600E, or NF1 mutations. Non-CSD-associated melanomas encompass acral and mucosal melanomas that usually do not show BRAF, NRAS, or NF1 mutations (triple wild-type), but in a subset may have KIT or SF3B1 mutations. To improve survival, these driver alterations can be treated with targeted therapy achieving significant antitumor activity. In recent years, relevant improvement in the prognosis and survival of patients with melanoma has been achieved, since the introduction of BRAF/MEK tyrosine kinase inhibitors and immune checkpoint inhibitors. In this review, we describe the current knowledge of molecular pathways and discuss current and potential therapeutic targets in melanoma, focusing on their clinical relevance of development. [ABSTRACT FROM AUTHOR]

Aims: The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. Methods and results: A total of 71 neoplasms showing spitzoid features (Spitz‐like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in‐situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF‐mutated naevus/low‐grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow‐up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression‐free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). Conclusions: The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status. [ABSTRACT FROM AUTHOR]

Background: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV). Objectives: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. Results: This retrospective study (2000–2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]–ANCA and 2.6% proteinase 3 [PR3]–ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3–ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. Conclusions: The identification of GPA presentations associated with MPO–ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult‐to‐diagnose patients based on their significant diagnostic yield. [ABSTRACT FROM AUTHOR]

Performance of the Xpert MTB/RIF Ultra Assay for Determining Cause of Death by TB in Tissue Samples Obtained by Minimally Invasive Autopsies To the Editor: An estimated 1.5 million deaths were attributable to TB in 2018.[1] However, some uncertainty exists as to the exact global figures, given that approximately 30% of incident cases are not diagnosed, and because of the difficulties of ascertaining TB as cause of death (CoD).[2] Undoubtedly, complete diagnostic autopsies (CDAs) constitute the gold standard for establishing a diagnosis of TB at death. In 31 patients, TB was the final CoD, 31 cases had TB disease at death but had died of another CoD, and in 18 cases DNA of M TB was detected but no histological lesions compatible with TB were found. [Extracted from the article]

This article discusses the use of SOX10 immunostaining in frozen tissue for the detection of lentigo maligna (LM), a type of melanoma. The study found that SOX10 had a sensitivity of 94% and a specificity of 100% in detecting LM when compared to conventional analysis using paraffin-embedded sections. The use of SOX10 immunostaining in frozen tissue can potentially reduce the need for multi-day procedures and improve the efficiency of margin control techniques. However, the study has limitations, including a small sample size and lack of blind assessment of the slides. Overall, SOX10 immunostaining shows promise in improving the detection of LM and streamlining surgical procedures. [Extracted from the article]

We report a case of Sneathia amnii as the causative agent of maternal chorioamnionitis and congenital pneumonia resulting in a late fetal death in Mozambique, with strong supportive postmortem molecular and histopathologic confirmation. This rare, fastidious gram-negative coccobacillus has been reported to infrequently cause abortions, stillbirths, and neonatal infections. [ABSTRACT FROM AUTHOR]

Purpose: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). Materials and methods: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. Results: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004–0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11–17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2–42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79–8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004–1.13], p = 0.048). Conclusions: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections. [ABSTRACT FROM AUTHOR]

Introduction: Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Study Design: Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Results: Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Conclusion: Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required. [ABSTRACT FROM AUTHOR]

Background: Line‐field confocal optical coherence tomography (LC‐OCT) is a new in vivo emerging technique that provides cellular resolution, allows deep imaging (400 μm) and produces real‐time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported. Aim: To describe the features of melanocytic lesions by LC‐OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings. Methods: Selected melanocytic benign lesions and melanomas were imaged in vivo with RCM and LC‐OCT at the Fundación Hospital Clinic (Barcelona, Spain). A minimum area of 4 × 4 mm (block image) at four depths (stratum granulosum, suprabasal, layer dermoepidermal junction and upper dermis) were acquired with RCM and a minimum of three cubes with LC‐OCT. Horizontal, vertical sections and three‐dimensional (3D) cubes of LC‐OCT were matched with RCM (Vivablock two‐dimensional composite mosaic) and histopathology, with ~5 μm lateral resolution accuracy (the same cell nuclei were measured in X, Y and Z) and evaluated by three observers experienced in using RCM and histopathology. Results: In total, 12 melanocytic tumours (2 in situ melanomas, 2 invasive melanomas, 4 atypical naevi, 2 intradermal naevi, 1 compound naevus and 1 junctional naevus) were included. High correlation with 5 μm accuracy between RCM and LC‐OCT was observed for each tumour. The 3D images of melanocytic lesions were obtained with cellular resolution and correlated with both RCM and histopathology, allowing an understanding of the architecture and precise correlation at the cellular level with RCM. Similarities between LC‐OCT and RCM for the described diagnostic features and architecture (nests of melanocytic cells, ringed and meshwork pattern, and cellular details of tumour cells as dendritic and pagetoid cells) were confirmed. The main advantage of diagnosis by RCM fixed probe was the ability to produce larger scans of the lesion using mosaicing compared with an LC‐OCT handheld probe. Conclusion: LC‐OCT allows the architectural and cellular description of different types of melanocytic lesions. LC‐OCT showed high correlation with histopathology (vertical sections) and RCM (horizontal sections) in melanocytic lesions. Diagnostic criteria for RCM were similar to those for LC‐OCT. [ABSTRACT FROM AUTHOR]

Objective: Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late‐onset uncharacterized autoinflammatory disease. Methods: Genetics studies were performed using Sanger sequencing and next‐generation sequencing (NGS) methods. In silico, in vitro, and ex vivo analyses were performed to determine the functional consequences of the detected variant. Results: We studied a 57‐year‐old woman who at the age of 47 years began to have recurrent episodes of fever, myalgias, arthralgias, diffuse abdominal pain, diarrhea, adenopathies, and systemic inflammation, which were relatively well controlled with anti–interleukin‐1 (anti‐IL‐1) drugs. NGS analyses did not detect germline variants in any of the known autoinflammatory disease–associated genes, but they identified the p.Ser171Phe NLRC4 variant in unfractionated blood, with an allele fraction (2–4%) compatible with gene mosaicism. Structural modeling analyses suggested that this missense variant might favor the open, active conformation of the NLRC4 protein, and in vitro and ex vivo analyses confirmed its propensity to oligomerize and activate the NLRC4 inflammasome, with subsequent overproduction of IL‐18. Conclusion: Our findings indicate that the postzygotic p.Ser171Phe NLRC4 variant is a plausible cause of the disease in the enrolled patient. Functional and structural studies clearly support, for the first time, its gain‐of‐function behavior, consistent with previously reported NLRC4 pathogenic variants. These novel findings should be considered in the diagnostic evaluation of patients with adult‐onset uncharacterized autoinflammatory disease. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. Methods From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. Conclusions MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation. Principal findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon. Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. Author summary: Histoplasmosis is a fungal infection caused by inhalation of spores of the fungus Histoplasma spp. It occurs in specific endemic areas, such as areas of USA, Africa and Latin America. However, the real burden of histoplasmosis remains unknown in many endemic regions. Clinically, histoplasmosis is frequently misdiagnosed as tuberculosis. The current study was carried out to explore the frequency and characteristics of Histoplasma infection in a series of autopsies conducted in the Brazilian Amazon. We found evidence of Histoplasma infection in one-third of the deceased patients. A significant proportion of the cases were disseminated infections, with extensive involvement and severe damage of most organs. All these disseminated infections occurred in HIV-positive patients. Strikingly, histoplasmosis was clinically missed in more than two-thirds of these patients and had an extremely high mortality. In conclusion, the high frequency and mortality of histoplasmosis, together with the frequent misdiagnosis of the disease, highlight the need of implementation of sensitive screening methods for Histoplasma in HIV patients in endemic areas. Additionally, antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. [ABSTRACT FROM AUTHOR]

Background: Oral premalignant lesions (OPML) are frequently extensive and multifocal leading high morbidity for patients. Although oral squamous carcinoma (OSCC) in non-smoker patients is increasing, little is known about OPML and the carcinogenesis process in these patients. The aims of the study were to insight and compare the clinicopathological and molecular characteristics of OPML of non-smoker and smoker patients from which one or multiple OSCC have developed.Methods: Eighty-one patients showing extensive and/or multifocal OPML were included in the survey. HPV and EBV were investigated by PCR and in situ hybridization respectively. Cytogenetic studies were performed by microarray in sequential progressive 30 lesions; p53 expression was investigated by immunohistochemistry.Results: The patients were 41 males and 40 females, ages ranging from 32 to 93 years (median 64); 43 (53%) were smokers. Non-smokers were more frequently female with a median age of 68, whereas smokers were men with a median age of 60 (P = 0.005). HPV and EBV were negative in all cases. The most consistent and earliest cytogenetic alterations in both non-smokers and smokers were loss of heterozygosity (LOH) and losses of locus harboring tumor suppressor genes. Progression to high-grade dysplasia and OSCC showed progressive addition of LOH, tumor suppressor losses, and oncogenic gains.Conclusion: Non-smoker patients are mostly elderly female and show oral carcinogenic pathways and outcomes similar to smoker patients. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS) is a simplified postmortem examination technique that has shown to be an adequate approach for cause of death investigation in low-resource settings. It requires relatively low level of infrastructures and can be performed by health professionals with no background in pathology. A training program has been developed for the Child Health and Mortality Prevention Surveillance (CHAMPS) network to guarantee standardization of specimen collection techniques, procedures, and laboratory methods. Methods The training program has included assessment of the site capacities and training on a standardized protocol of MITS sampling and histological processing. The project has also introduced a program of training for trainers for the personnel from Mozambique. To guarantee the adequacy of the procedure in each site, a trainer accompanied the local teams when the activities started. Training outcomes were assessed by evaluating the quality of the samples obtained and the quality of the slides produced locally. Results Between June 2016 and October 2018, the laboratories of 7 sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) have been evaluated and upgraded. Training has been delivered to 63 staff members from all sites. More than 600 MITS procedures have been performed. The quantity of tissue obtained in the MITS by the local teams was sufficient or abundant in 73%, and 87% of the slides were considered as technically acceptable or excellent. Conclusions Satisfactory standardization of MITS and histology procedures has been achieved across all CHAMPS sites through organized capacity-building plans. [ABSTRACT FROM AUTHOR]

Introduction. During their professional training, medical students are subject to diverse stress-causing factors such as academic demands and a highly competitive environment which may threaten their mental health. Objective. Identify the presence of depressive symptoms in medical students in a public university in Mexico. Method. Descriptive cross-sectional study of a random sample of 203 medical students at the Universidad Autónoma de Baja California from February to April 2018. The PHQ - 9 scale was used, and a cut-off score of ≥ 10 was employed as positive for depressive symptoms. Basic descriptive statistics were utilized to analyze sociodemographic variables such as gender, academic advancement, stage of training (basic science vs. clinical), and the prevalence of the five different categories of the scale. Results. Of the medical students surveyed, 20.2% were found positive for depressive symptoms and 7.9% (16) had severe or moderately severe symptoms. Female gender increased the risk of presenting symptoms (OR = 3.5, 95% CI [1.6, 7.6]). Discussion. Despite the fact that the prevalence of depressive symptoms encountered was similar to that reported worldwide, it is troubling that one fifth of the surveyed students presented depressive symptoms. These results may justify implementation of preventive strategies by academic authorities to improve student mental health, and maybe even for early detection of risk of major depressive disorder. [ABSTRACT FROM AUTHOR]

Occupational accidents presented in the different activities developed within the companies not only affect the health of the collaborators but they are linked to a series of consequences that affect the normal development of an organization. In the case of occupational diseases acquired and developed at work it is identified that there are factors at work (unsafe conditions) that facilitate the presence of conditions in the bodies of people who in the long term become occupational diseases, in the industry metallurgy the risks are daily in the processes in which there is evidence of extreme temperature risks, noise and lighting among others; It should be noted that a work related illness can develop not only because it is exposed to the aforementioned risks, but it can also be the consequence of an accident at work that, in the short or long term, causes deterioration in the organism and capacities of the collaborator. [ABSTRACT FROM AUTHOR]

Aedes aegypti L. (Diptera: Culicidae) is a mosquito broadly found in tropical and temperate areas of the world. It is the main vector of dengue, chikungunya, zika and yellow fever (urban cycle), among other viruses. Aedes aegypti immatures develop in water holding containers, and frequently use artificial containers in urban settings as larval habitat. Ovitraps are artificial oviposition sites, a tool developed for mosquito population surveillance and to assess effectiveness of control measures. The preference for different oviposition substrate materials was assessed in the field, in two localities of Salta province, northern Argentina, where dengue outbreaks are frequent. The proportion of positive traps did not differ between oviposition substrates. However, higher numbers of eggs were laid in cotton fabric and velour paper, which were better than wooden paddle and blotting paper if the aim was to maximize the numbers of eggs collected. The results also evidenced that substrate preference for oviposition did not differ between geographic regions. [ABSTRACT FROM AUTHOR]

Background: The minimally invasive autopsy (MIA) is being investigated as an alternative to the complete diagnostic autopsy (CDA), gold standard for CoD determination, in settings where CDA is unfeasible and/or unacceptable. We aimed to explore healthcare providers’ views and perceptions on theoretical and factual acceptability of the CDA and the MIA. Methods: A qualitative study, combining ethnographic and grounded-theory approaches, was conducted within a project aiming to validate the MIA tool against the CDA for CoD investigation. We present data on in-depth and semi-structured interviews of 33 healthcare providers operating within the formal and informal health services in Southern Mozambique. MIA perception was analysed through the theory of diffusion of innovations. Results: All participants considered CDA useful for CoD determination. CDA was perceived reliable, but the unpleasant nature of the procedure and its associated infection risk were the main perceived disadvantages. Participants considered the MIA simple, easy and quick to perform; likely to meet families’ expectations to know the CoD, and able to provide evidence-based knowledge for disease management. Concerns were raised on its reliability compared to the CDA. Family's emotional status and accessibility to decision-makers were mentioned as principal barriers for MIA performance. The main jeopardizing factors for MIA implementation were the shortage of required resources and the significant proportion of people dying at home. Key facilitators for MIA acceptance included the need for the support from community and religious leaders, provision of clear information to the community, and accompaniment to bereaved families. Conclusions: Healthcare providers consider the MIAs potentially more acceptable and feasible than CDAs in places where the latter have shown significant implementation challenges. A clear understanding of healthcare provider’s perceived barriers and facilitators for conducting post-mortem procedures in general, and MIAs in particular, will shed light on their future field implementation for more robust mortality surveillance. [ABSTRACT FROM AUTHOR]

Background: Despite global health efforts to reduce maternal mortality, rates continue to be unacceptably high in large parts of the world. Feasible, acceptable, and accurate postmortem sampling methods could provide the necessary evidence to improve the understanding of the real causes of maternal mortality, guiding the design of interventions to reduce this burden.Methods and Findings: The validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in an observational study in 57 maternal deaths by comparing the results of the MIA with those of the gold standard (complete diagnostic autopsy [CDA], which includes any available clinical information). Concordance between the MIA and the gold standard diagnostic categories was assessed by the kappa statistic, and the sensitivity, specificity, positive and negative predictive values and their 95% confidence intervals (95% CI) to identify the categories of diagnoses were estimated. The main limitation of the study is that both the MIA and the CDA include some degree of subjective interpretation in the attribution of cause of death. A cause of death was identified in the CDA in 98% (56/57) of cases, with indirect obstetric conditions accounting for 32 (56%) deaths and direct obstetric complications for 24 (42%) deaths. Nonobstetric infectious diseases (22/32, 69%) and obstetric hemorrhage (13/24, 54%) were the most common causes of death among indirect and direct obstetric conditions, respectively. Thirty-six (63%) women were HIV positive, and HIV-related conditions accounted for 16 (28%) of all deaths. Cerebral malaria caused 4 (7%) deaths. The MIA identified a cause of death in 86% of women. The overall concordance of the MIA with the CDA was moderate (kappa = 0.48, 95% CI: 0.31-0.66). Both methods agreed in 68% of the diagnostic categories and the agreement was higher for indirect (91%) than for direct obstetric causes (38%). All HIV infections and cerebral malaria cases were identified in the MIA. The main limitation of the technique is its relatively low performance for identifying obstetric causes of death in the absence of clinical information.Conclusions: The MIA procedure could be a valuable tool to determine the causes of maternal death, especially for indirect obstetric conditions, most of which are infectious diseases. The information provided by the MIA could help to prioritize interventions to reduce maternal mortality and to monitor progress towards achieving global health targets. [ABSTRACT FROM AUTHOR]

Background: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. In this study, we have tested this hypothesis by generating mice with myeloid C/EBPβ deficiency.Methods: Mice with myeloid C/EBPβ deficiency were generated by crossing LysMCre and C/EBPβfl/fl mice. Primary microglial cultures from C/EBPβfl/fl and LysMCre-C/EBPβfl/fl mice were treated with lipopolysaccharide ± interferon γ (IFNγ) for 6 h, and gene expression was analyzed by RNA sequencing. Gene expression and C/EBPβ deletion were analyzed in vivo in microglia isolated from the brains of C/EBPβfl/fl and LysMCre-C/EBPβfl/fl mice treated systemically with lipolysaccharide or vehicle. Mice of LysMCre-C/EBPβfl/fl or control genotypes were subjected to experimental autoimmune encephalitis and analyzed for clinical signs for 52 days. One- or two-way ANOVA or Kruskal-Wallis with their appropriate post hoc tests were used.Results: LysMCre-C/EBPβfl/fl mice showed an efficiency of C/EBPβ deletion in microglia of 100 and 90% in vitro and in vivo, respectively. These mice were devoid of female infertility, perinatal mortality and reduced lifespan that are associated to full C/EBPβ deficiency. Transcriptomic analysis of C/EBPβ-deficient primary microglia revealed C/EBPβ-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. In vivo, microglial expression of the pro-inflammatory genes Cybb, Ptges, Il23a, Tnf and Csf3 induced by systemic lipopolysaccharide injection was also blunted by C/EBPβ deletion. CNS expression of C/EBPβ was upregulated in experimental autoimmune encephalitis and in multiple sclerosis samples. Finally, LysMCre-C/EBPβfl/fl mice showed robust attenuation of clinical signs in experimental autoimmune encephalitis.Conclusion: This study provides new data that support a central role for C/EBPβ in the biology of activated microglia, and it offers proof of concept for the therapeutic potential of microglial C/EBPβ inhibition in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Introduction: CO2 transoral laser microsurgery (CO2-TOLMS) has pushed the indications of partial surgery of the larynx regardless the age of the patient.Objective: To evaluate the complications and the oncologic and functional outcomes of CO2-TOLMS in patients older and younger than 70 years.Methods: Retrospective analysis of 1244 consecutive laryngeal carcinomas treated with CO2-TOLMS. Complications, length of hospitalization, functional and survival outcomes were evaluated.Results: The mean age was 64.2 ± 11.1 years (20-96). Four hundred and sixteen patients were older than 70 years and 104 older than 80 years. The main location was the glottis (912), followed by the supraglottis (332). There were no differences in pT classification between the age groups. No differences were observed in voice outcomes. A higher rate of signs of aspiration at the glottic location was observed for those older than 70 years (2.1 % vs 5 %, p = 0.027). The need for definitive gastrostomy in supraglottic tumours was higher in those older than 70 years (0 % vs 6.5 %, p: 0.001). In the glottis, no differences in tracheostomy or gastrostomy rates were observed. Five-year overall survival was lower in the older than 70 years. No differences in disease-specific survival were observed in early stages for both locations, but a lower survival was observed in stage III glottic cancer for the older than 70 years.Conclusions: CO2-TOLMS is a valid treatment for laryngeal carcinomas in the elderly, with a reduced number of complications and good functional and oncologic outcomes. [ABSTRACT FROM AUTHOR]

In developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and treatment guidelines. We aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (MIA) procedures and to assess their performance. Thirty MIAs performed in adults at Maputo Central Hospital in Southern Mozambique were included in the analysis. Microbiological tests included a universal screening for HIV, hepatitis B and C viruses, Plasmodium falciparum , and bacterial/fungal culture. In addition, a variety of molecular microbiology assays guided by the histological results were performed in blood, cerebrospinal fluid and a variety of tissue samples including liver, lung and central nervous system. The combination of culture-based methods together with molecular microbiological assays led to the identification of 17 out of 19 (89.5%) of the infectious deaths. Microorganisms identified included Mycobacterium tuberculosis , Toxoplasma gondii , Pneumocystis jiroveci , Cryptococcus neoformans , hepatitis B virus, human herpesvirus 8, cytomegalovirus, Streptococcus pneumoniae , Streptococcus dysgalactiae , Ryzopus oryzae , and Acinetobacter baumannii . The combination of classical cultures, serological tests and molecular assays performed in samples obtained through MIA allows the identification of most infectious agents causing death. [ABSTRACT FROM AUTHOR]

Background: Very limited information is available regarding the incidence of cancer in sub-Saharan Africa. We analyzed changes in cancer patterns from 1991 to 2008 in Maputo (Mozambique). Methods: We calculated the rates of incidence of different cancer sites by sex in the 5-year age-group of the population of Maputo city as well as age-standardized rates (ASRs) and average annual percentage changes (AAPC). Results: Over the 18-year study period a total of 12,674 cases of cancer (56.9% females) were registered with an overall increase in the risk of cancer in both sexes. In males, the most common cancers were those of the prostate, Kaposi sarcoma (KS) and the liver. Prostate cancer showed the most dramatic increase over the whole study period (AAPC +11.3%; 95% CI: 9.7–13.0), with an ASR of 61.7 per 105 in 2003–2008. In females, the most frequent cancers were of the uterine cervix, the breast and KS, with the former increasing along the whole study period (AAPC + 4.7%; 95% CI: 3.4–6) with an ASR of 62.0 per 105 in 2003–2008 as well as breast cancer (AAPC +6.5%; 95%CI: 4.3–8.7). Conclusions: Overall, the risk of cancer rose in both sexes during the study period, particularly among cancers associated with westernization of lifestyles (prostate, breast), combined with increasingly rising incidences or limited changes in cancers associated with infection and poverty (uterine cervix, liver). Moreover, the burden of AIDS-associated cancers has shown a marked increase. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 19-year-old patient who experienced spleen rupture due to an untreated infection with Plasmodium vivax, a parasite that causes malaria. The study examined the patient's spleen and found high levels of the parasite in the red pulp. Additionally, the study observed an increase in plasmablasts, a type of immune cell, in the spleen. These findings suggest that P. vivax infections can cause changes in the spleen that resemble lymphoma and may impact the development of immunity against the parasite. [Extracted from the article]

The article presents a case study of a 19-year-old nonimmune patient with Plasmodium vivax monoinfection supported by polymerase chain reaction (PCR) in his peripheral blood and spline section. It states that the initial diagnosis revealed anemia and thrombocytopenia, and he was transferred to a tertiary-care infectious diseases reference center. The patient submits to splenectomy due to profuse intra-abdominal hemorrhage.

Abstract: Objective: Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm. Methods: All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n=57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16INK4a expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16INK4a was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p<.001). FIGO stage was associated with DFS (p=.042) and OS (p=.008). HPV-positive tumors showed better DFS (p=.042) and OS (p=.035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR=0.26; 95% CI 0.10–0.69; p=0.006). Conclusions: HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16INK4a immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC. [Copyright &y& Elsevier]

Abstract: Objective: Less than 5% of women with cervical or vaginal biopsy proven high-grade squamous intraepithelial lesions (HG-SIL) show a negative Hybrid Capture 2 (HC2) result. We analyzed 1) human papillomavirus (HPV) genotypes by PCR in order to determine whether these cases represent infections by common or unusual types, and 2) the clinical, colposcopic and pathological differential characteristics of these patients. Methods: 646 women with a histological diagnosis of HG-SIL and a HC2 test collected within 6months prior to the diagnosis were identified. Patients with a negative HC2 result were selected. HPV was typed in the biopsy specimen in all by PCR using SPF10 and GP5+/6+ primers, and p16INK4a immunostaining was performed. The clinical and colposcopy findings of these women were compared with a control group of HG-SIL with positive HC2 result. Results: 20 women (3.1%) with HG-SIL had a negative HC2. All biopsies were positive for p16INK4. PCR analysis detected HPV types included in HC2 test in 55% of the cases, with an identical percentage of common viruses between women with relative light unit values above or below 0.40 (p=.361). False negative HC2 tests increased with age (p=.002) and were more frequent in patients with non satisfactory colposcopy or small sized lesions (p<.001). Conclusion: A negative HC2 test is an infrequent event in women with HG-SIL. Common HPV types are identified in over half of the cases. Older women and patients with small lesions or non satisfactory colposcopy have a higher rate of HC2 negative results. [Copyright &y& Elsevier]

Abstract: Background: Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy. Methods: All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n =98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16INK4a expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16INK4a stained 100% HPV-positive and 1.3% HPV-negative tumors (p <.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5years; p =.831), or OS (67.2% vs. 71.4% at 5years; p =.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III–IV (p =.002), lymph node metastasis (p =.030), size≥20mm (p =.023), invasion depth (p =.020) and ulceration (p =.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61). Conclusions: HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women. [Copyright &y& Elsevier]

Introduction: Typhoid fever is an important public health problem in many low-income countries where asymptomatic carriers play an important role in its dissemination. The bacterium causing typhoid fever can live in the gallstones of asymptomatic persons after the infection. These carriers are reservoirs of S. Typhi, are highly contagious, and spread the disease through the secretion of bacteria in feces and urine. The aim of this study was to determine the carrier rate in an area of Mozambique. Methodology: The presence of S. Typhi was analyzed in gallbladder samples obtained from 99 adult corpses (in-hospital deaths) from Mozambique by gold-standard culture and polymerase chain reaction (PCR). Results: Only one sample was positive with the culture. However, nine additional samples were positive by PCR and confirmed by DNA sequencing. Thus, the prevalence of S. Typhi was 10.1% (10/99). Conclusions: We report a high prevalence of S. Typhi in gallbladders among adult autopsy cases from Mozambique. [ABSTRACT FROM AUTHOR]