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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: 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]

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]

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]

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: 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]

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]

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]

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.

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]

To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants. Genotypic analysis by Mycobacterial Interspersed Repetitive-Unit–Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden. Genotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue. Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed. [ABSTRACT FROM AUTHOR]

Simple Summary: Emerging evidence points to succinate as an important oncometabolite in cancer development; however, the contribution of the succinate-SUCNR1 axis to cancer progression remains unclear. Head and neck squamous cell carcinoma (HNSCC) is associated with disease and treatment-related morbidity so there is an urgent need for innovation in treatment and diagnosis practices. Our aim was to evaluate the potential of the succinate-related pathway as a diagnostic and prognostic biomarker in HNSCC. The circulating succinate levels are increased in HNSCC, being a potential noninvasive biomarker for HNSCC diagnosis. Moreover, the succinate receptor (SUCNR1) and genes related to succinate metabolism, which are predominantly expressed in the tumoral mucosa as compared with healthy tissue, are positively associated with plasma succinate. Remarkably, we found that SUCNR1 and SDHA expression levels predict prognosis. Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9–100.0] vs. 16.7% [95% CI: 0.0–44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis. [ABSTRACT FROM AUTHOR]