Complement genes contribute sex-biased vulnerability in diverse disorders.

Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3-6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.

BCFtools/liftover: an accurate and comprehensive tool to convert genetic variants across genome assemblies.

MOTIVATION: Many genetics studies report results tied to genomic coordinates of a legacy genome assembly. However, as assemblies are updated and improved, researchers are faced with either realigning raw sequence data using the updated coordinate system or converting legacy datasets to the updated coordinate system to be able to combine results with newer datasets. Currently available tools to perform the conversion of genetic variants have numerous shortcomings, including poor support for indels and multi-allelic variants, that lead to a higher rate of variants being dropped or incorrectly converted. As a result, many researchers continue to work with and publish using legacy genomic coordinates. RESULTS: Here we present BCFtools/liftover, a tool to convert genomic coordinates across genome assemblies for variants encoded in the variant call format with improved support for indels represented by different reference alleles across genome assemblies and full support for multi-allelic variants. It further supports variant annotation fields updates whenever the reference allele changes across genome assemblies. The tool has the lowest rate of variants being dropped with an order of magnitude less indels dropped or incorrectly converted and is an order of magnitude faster than other tools typically used for the same task. It is particularly suited for converting variant callsets from large cohorts to novel telomere-to-telomere assemblies as well as summary statistics from genome-wide association studies tied to legacy genome assemblies. AVAILABILITY AND IMPLEMENTATION: The tool is written in C and freely available under the MIT open source license as a BCFtools plugin available at http://github.com/freeseek/score.

Two distinct ways to form long-term object recognition memory during sleep and wakefulness.

Memory consolidation is promoted by sleep. However, there is also evidence for consolidation into long-term memory during wakefulness via processes that preferentially affect nonhippocampal representations. We compared, in rats, the effects of 2-h postencoding periods of sleep and wakefulness on the formation of long-term memory for objects and their associated environmental contexts. We employed a novel-object recognition (NOR) task, using object exploration and exploratory rearing as behavioral indicators of these memories. Remote recall testing (after 1 wk) confirmed significant long-term NOR memory under both conditions, with NOR memory after sleep predicted by the occurrence of EEG spindle-slow oscillation coupling. Rats in the sleep group decreased their exploratory rearing at recall testing, revealing successful recall of the environmental context. By contrast, rats that stayed awake after encoding showed equally high levels of rearing upon remote testing as during encoding, indicating that context memory was lost. Disruption of hippocampal function during the postencoding interval (by muscimol administration) suppressed long-term NOR memory together with context memory formation when animals slept, but enhanced NOR memory when they were awake during this interval. Testing remote recall in a context different from that during encoding impaired NOR memory in the sleep condition, while exploratory rearing was increased. By contrast, NOR memory in the wake rats was preserved and actually superior to that after sleep. Our findings indicate two distinct modes of long-term memory formation: Sleep consolidation is hippocampus dependent and implicates event-context binding, whereas wake consolidation is impaired by hippocampal activation and strengthens context-independent representations.

The hippocampus is crucial for forming non-hippocampal long-term memory during sleep.

There is a long-standing division in memory research between hippocampus-dependent memory and non-hippocampus-dependent memory, as only the latter can be acquired and retrieved in the absence of normal hippocampal function1,2. Consolidation of hippocampus-dependent memory, in particular, is strongly supported by sleep3-5. Here we show that the formation of long-term representations in a rat model of non-hippocampus-dependent memory depends not only on sleep but also on activation of a hippocampus-dependent mechanism during sleep. Rats encoded non-hippocampus-dependent (novel-object recognition6-8) and hippocampus-dependent (object-place recognition) memories before a two-hour period of sleep or wakefulness. Memory was tested either immediately thereafter or remotely (after one or three weeks). Whereas object-place recognition memory was stronger for rats that had slept after encoding (rather than being awake) at both immediate and remote testing, novel-object recognition memory profited from sleep only three weeks after encoding, at which point it was preserved in rats that had slept after encoding but not in those that had been awake. Notably, inactivation of the hippocampus during post-encoding sleep by intrahippocampal injection of muscimol abolished the sleep-induced enhancement of remote novel-object recognition memory. By contrast, muscimol injection before remote retrieval or memory encoding had no effect on test performance, confirming that the encoding and retrieval of novel-object recognition memory are hippocampus-independent. Remote novel-object recognition memory was associated with spindle activity during post-encoding slow-wave sleep, consistent with the view that neuronal memory replay during slow-wave sleep contributes to long-term memory formation. Our results indicate that the hippocampus has an important role in long-term consolidation during sleep even for memories that have previously been considered hippocampus-independent.

Inter-parental conflict and empathy in early adolescence as predictors of dating violence perpetration in adolescence and adulthood.

Witnessing inter-parental conflict is associated with dating violence perpetration in late adolescence and adulthood. This relationship may be moderated by adolescents' empathy, with more empathic youth viewing their parents' conflict behavior as less acceptable, and thus refraining from dating violence perpetration. This study sought to determine if empathy buffers the effects of inter-parental conflict in early adolescence on expected dating violence perpetration in early adolescence and actual dating violence perpetration in late adolescence and adulthood. Moreover, this study tested if expected dating violence perpetration in early adolescence and dating violence perpetration in late adolescence mediate the effects of inter-parental conflict and empathy on dating violence perpetration in adulthood. Sex differences in these relationships were also examined. The sample included 412 adolescents (52% male, 73% Black, 25% White, 2% Other) who participated at three time points between 2006 and 2022 (T1-T3, Mean age = 13, 18, 28 years). Results indicated that higher inter-parental conflict and lower empathy were associated with higher expected dating violence perpetration at T1 in both males and females. Inter-parental conflict at T1 predicted higher dating violence perpetration at T3 through expected dating violence perpetration at T1 and dating violence perpetration at T2. Empathy at T1 predicted lower dating violence perpetration at T3 directly and also indirectly through lower expected dating violence at T1 and lower dating violence perpetration at T2 in both sexes. There were no interaction effects of inter-parental conflict and empathy on expected or actual dating violence perpetration at any age.

Interpersonal school violence and mother-child communication about violence in relation to empathy in early adolescence.

INTRODUCTION: Exposure to interpersonal violence at school has been linked with lower empathy, but less is known about factors that may moderate this relationship. Positive parent-child communication has been associated with higher empathy during adolescence and children of parents that communicate their disapproval of violent behavior respond more peacefully in situations involving violence. Mother-child communication about violence may therefore reduce the risk of desensitization to violent behavior and promote empathy in youth that are frequently exposed to violence. Thus, this study examines whether mother-child communication about violence mitigates the association between exposure to interpersonal school violence and adolescents' empathy. METHODS: This study addressed this question using a diverse sample of early adolescents from the Southeastern United States in 2003 (N = 642; mean age 11.3 years; 52% male; 76% Black, 22% non-Hispanic White). Adolescents reported on how often they witness or experience interpersonal violence at school and how often they communicate with their mother about violence and how to avoid it. Adolescents also self-reported on their level of empathy. RESULTS: Results from a hierarchical regression model showed that exposure to interpersonal school violence and lower mother-child communication about violence were uniquely associated with lower empathy, but communication about violence did not moderate the link between interpersonal school violence exposure and empathy. There were no sex differences in these relationships. CONCLUSIONS: Contrary to the hypothesis, youth who experience and witness interpersonal violence at school show lower empathy independent of whether youth communicate with their mother about violence and responding to violent situations.

Transformation of agricultural wastes into functional oligosaccharides using enzymes and emerging technologies.

INTRODUCTION: Pectin-oligosaccharides (POS) serve diverse purposes as a food ingredient, antimicrobial and biostimulant in plants, and their functionality is linked to the degree of esterification. Grape and broccoli wastes emerge as environmentally friendly alternatives to obtaining pectin, serving as a sustainable source to producing POS. For example, microwaves have proven to be an effective and sustainable method to extract polysaccharides from plant matrices. OBJECTIVE: This work aims to use grape and broccoli wastes as alternative sources for obtaining pectin by microwave-assisted extraction and biotransformation into POS, which possess biological properties. MATERIAL AND METHODS: The extraction conditions were identified at a power of 400 W, 300 s for the extraction of pectin from grape pomace and broccoli waste. Biotransformation of pectins into POS, using commercial enzyme preparations (Viscozyme L and Pectinase). Characterisation was carried out by Fourier-transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. RESULTS: Physicochemical analysis indicated grape pomace and broccoli waste pectins had galacturonic acid content of 63.81 ± 1.67 and 40.83 ± 2.85 mg 100 mg-1, low degree of esterification of 34.89% and 16.22%, respectively. Biotransformation of pectins into POS resulted in a 20% hydrolysis rate. The main enzymatic activity was polygalacturonase for the degradation of the main structure of the pectin. CONCLUSION: Production of POS from agro-industrial wastes by emerging technologies, such as the combined use of microwave-assisted extraction and enzymatic processes, represents an alternative method for the generation of bioactive compounds with distinctive properties suitable for different applications of interest.

Ancestry-agnostic estimation of DNA sample contamination from sequence reads.

Detecting and estimating DNA sample contamination are important steps to ensure high-quality genotype calls and reliable downstream analysis. Existing methods rely on population allele frequency information for accurate estimation of contamination rates. Correctly specifying population allele frequencies for each individual in early stage of sequence analysis is impractical or even impossible for large-scale sequencing centers that simultaneously process samples from multiple studies across diverse populations. On the other hand, incorrectly specified allele frequencies may result in substantial bias in estimated contamination rates. For example, we observed that existing methods often fail to identify 10% contaminated samples at a typical 3% contamination exclusion threshold when genetic ancestry is misspecified. Such an incomplete screening of contaminated samples substantially inflates the estimated rate of genotyping errors even in deeply sequenced genomes and exomes. We propose a robust statistical method that accurately estimates DNA contamination and is agnostic to genetic ancestry of the intended or contaminating sample. Our method integrates the estimation of genetic ancestry and DNA contamination in a unified likelihood framework by leveraging individual-specific allele frequencies projected from reference genotypes onto principal component coordinates. Our method can also be used for estimating genetic ancestries, similar to LASER or TRACE, but simultaneously accounting for potential contamination. We demonstrate that our method robustly estimates contamination rates and genetic ancestries across populations and contamination scenarios. We further demonstrate that, in the presence of contamination, genetic ancestry inference can be substantially biased with existing methods that ignore contamination, while our method corrects for such biases.

Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. METHODS: We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. RESULTS: We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). CONCLUSIONS: Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

An Unusual Benign Uterine Stromal Spindle Cell Tumor Harboring JAZF1::BCORL1.

Uterine mesenchymal lesions demonstrate various underlying genomic alterations involving MED12 , JAZF1 , YWHAE , BCOR , and ALK genes, among others. Recent publications describe a subset of high-grade endometrial stromal sarcoma lesions harboring BCORL1 gene aberrations including JAZF1::BCORL1 . Herein, we present an unusual benign endomyometrial spindle cell lesion that defies classificatory efforts by demonstrating mixed histomorphologic and immunohistochemical features of endometrial stromal nodule, leiomyoma, and uterine inflammatory myofibroblastic tumor while harboring a JAZF1::BCORL1 . The lesion was found in a 43-yr-old woman with pelvic pain and heavy menses as a 5.5 cm well-circumscribed ulcerated mass fungating from the cervical os. Microscopic examination revealed a polypoid, well-circumscribed, moderately cellular endomyometrial tumor composed by bland spindle cells haphazardly disposed within a slightly edematous stroma enriched by a delicate network of thin-walled vessels that were occasionally encircled by the tumor cells. Unequivocal evidence of tongue-like growth pattern into the myometrium, tumor-type necrosis or increased mitotic activity was not identified after sampling the entire lesion. The lesion showed patchy immunoreactivity for both smooth muscle actin-alpha and desmin while negative for CD10, HMB45, ALK (D5F3), and BCOR. An Archer FusionPlex panel assay demonstrated a fusion involving both exons 4 from the JAZF1 and BCORL1 genes. The JAZF1::BCORL1 has not, to the best of our knowledge, been previously reported in a benign/low-grade mesenchymal uterine lesion.

Pigmented intraepithelial Merkel cell carcinoma mimicking melanoma in situ.

Merkel cell carcinoma (MCC) is a rare neoplasm that arises in the skin of elderly patients on sun-exposed areas such as the head, neck, and extremities. Involvement of the epidermis by tumor cells is a relatively uncommon phenomenon. However, a few cases have been reported of Merkel cell carcinoma in situ (MCCIS) in which tumor cells are confined exclusively to the epidermis without dermal involvement. Herein, we present a peculiar MCCIS lesion in a 66-year-old man composed of tumor cells in a nested and lentiginous growth pattern, exhibiting variable quantities of intracytoplasmic dusty brown pigment consistent with melanin, thus closely mimicking melanoma in situ. In addition, the lesion was associated with invasive squamous cell carcinoma, which has not been previously reported in the literature. An extensive search of the PubMed-indexed, English-language literature yielded only 17 case reports of MCCIS without documented invasion in which clinical data were available. Out of the cases with available clinical information, individuals with strict MCCIS (n = 13) showed no evidence of recurrence or metastases. The median follow-up time in the cases with available data (n = 9) was 12 months (mean 12.8 months, range 6-21). Thus, MCCIS without invasion may have a favorable clinical course in contrast to invasive MCC tumors.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact assessment of synthesis parameter stirring speed in final physicochemical properties of PU microcapsules incorporated into epoxy matrixes.

A considerable number of papers have been published to assess self-healing capacity of several materials, as well as several applications in different areas. However, the impact assessment of changing synthesis parameters of microcapsules, hollow fibers or microvascular systems in its final physicochemical properties are still an emerging research field. This current paper presents a synthesis process of PU microcapsules containing TDI as core agent and the characterization of microcapsules physicochemical properties. During the synthesis, the reaction parameter stirring speed was changed to assess the impact that this parameter has in the final microcapsules' physicochemical properties. Microcapsules were characterized by FT-IR, TGA and image analysis (OM and SEM). Additionally, microcapsules were incorporated to an epoxy matrix (5% weight/weight) to assess the impact in the final physicochemical and mechanical matrix properties. Epoxy-based test specimens were also obtained within aramid and silica, which are traditional reinforcing loads in rubber synthesis. Final mechanical properties of matrixes within aramid and silica were compared to the properties of matrixes within microcapsules to determine what kind of behavior the microcapsules have when incorporated to epoxy matrixes.

Synthesis and characterization of Poly(urea-formaldehyde) microcapsules with 5-ethylidene-2-norbornene as self-healing agent and potential use in polymeric composites.

This study describes a methodology to prepare and characterize PUF [poly(urea formaldehyde)] microcapsules containing 5-ethylidene-2-norbornene (ENB) as self-healing agent, as well as the compatibility evaluation of ENB in the presence of Grubb's catalyst with an epoxy matrix. First, the results of an adhesion assay by lap shear proved chemical compatibility between the epoxy matrix and self-healing agent in the presence of Grubb's catalyst. After evaluating the chemical compatibility, microcapsules with ENB were synthesized in an oil-in-water emulsion system. Thereafter, the microcapsules were morphologically, chemically and thermally characterized in which a granulometric dispersion between 30-140 µm and an average size of 69.8 ± 4.9 µm were observed. The SEM (scanning electron microscope) results showed that the average thickness of microcapsules shell was 3.6 ± 0.4 µm. The thermogravimetric analysis (TGA) showed that microcapsules are susceptible to rupture and consequent ENB release in temperatures greater than 230 °C, demonstrating that microcapsules are suitable for applications in materials with self-healing capacity.

Trypanosoma cruzi in Mexican Neotropical vectors and mammals: wildlife, livestock, pets, and human population.

OBJECTIVE: To provide primary evidence of Trypanosoma cruzi landscape genetics in the Mexican Neotropics. MATERIALS AND METHODS: Trypanosoma cruzi and discrete typing units (DTU) prevalence were analyzed in landscape communities of vectors, wildlife, livestock, pets, and sympatric human populations using endpoint PCR and sequencing of all relevant amplicons from mitochondrial (kDNA) and nuclear (ME, 18S, 24Sα) gene markers. RESULTS: Although 98% of the infected sample-set (N=2 963) contained single or mixed infections of DTUI (TcI, 96.2%) and TcVI (22.6%), TcIV and TcII were also identified. Sensitivity of individual markers varied and was dependent on host taxon; kDNA, ME and 18S combined identified 95% of infections. ME genotyped 90% of vector infections, but 60% of mammals (36% wildlife), while neither 18S nor 24Sα typed more than 20% of mammal infections. CONCLUSION: Available gene fragments to identify or genotype T. cruzi are not universally sensitive for all landscape parasite populations, highlighting important T. cruzi heteroge- neity among mammal reservoir taxa and triatomine species.

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

The study of neurodevelopmental molecular mechanisms in schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously utilized cell lines with neural progenitor properties (CNON) derived from the superior or middle turbinates of patients with schizophrenia and control groups to study schizophrenia-specific gene expression. In this study, we analyzed single-cell RNA seq data from two CNON cell lines (one derived from an individual with schizophrenia (SCZ) and the other from a control group) and two biopsy samples from the middle turbinate (MT) (also from an individual with SCZ and a control). We compared our data with previously published data regarding the olfactory neuroepithelium and demonstrated that CNON originated from a single cell type present both in middle turbinate and the olfactory neuroepithelium and expressed in multiple markers of mesenchymal cells. To define the relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data derived from an embryonic brain and found that the expression profile of the CNON closely matched the expression profile one of the cell types in the embryonic brain. Finally, we evaluated the differences between SCZ and control samples to assess the utility and potential benefits of using CNON single-cell RNA seq to study the etiology of schizophrenia.

Presence and potential distribution of malaria-infected New World primates of Costa Rica.

BACKGROUND: In South and Central America, Plasmodium malariae/Plasmodium brasilianum, Plasmodium vivax, Plasmodium simium, and Plasmodium falciparum has been reported in New World primates (NWP). Specifically in Costa Rica, the presence of monkeys positive to P. malariae/P brasilianum has been identified in both captivity and in the wild. The aim of the present study was to determine the presence of P. brasilianum, P. falciparum, and P. vivax, and the potential distribution of these parasites-infecting NWP from Costa Rica. METHODS: The locations with PCR (Polymerase Chain Reaction) positive results and bioclimatic predictors were used to construct ecological niche models based on a modelling environment that uses the Maxent algorithm, named kuenm, capable to manage diverse settings to better estimate the potential distributions and uncertainty indices of the potential distribution. RESULTS: PCR analysis for the Plasmodium presence was conducted in 384 samples of four primates (Howler monkey [n = 130], White-face monkey [n = 132], Squirrel monkey [n = 50], and red spider monkey [n = 72]), from across Costa Rica. Three Plasmodium species were detected in all primate species (P. falciparum, P. malariae/P. brasilianum, and P. vivax). Overall, the infection prevalence was 8.9%, but each Plasmodium species ranged 2.1-3.4%. The niche model approach showed that the Pacific and the Atlantic coastal regions of Costa Rica presented suitable climatic conditions for parasite infections. However, the central pacific coast has a more trustable prediction for malaria in primates. CONCLUSIONS: The results indicate that the regions with higher suitability for Plasmodium transmission in NWP coincide with regions where most human cases have been reported. These regions were also previously identified as areas with high suitability for vector species, suggesting that enzootic and epizootic cycles occur.

Spectral Reflectance as a Unique Tissue Identifier in Healthy Humans and Inhalation Injury Subjects.

Tracheal intubation is the preferred method of airway management, a common emergency trauma medicine problem. Currently, methods for confirming tracheal tube placement are lacking, and we propose a novel technology, spectral reflectance, which may be incorporated into the tracheal tube for verification of placement. Previous work demonstrated a unique spectral profile in the trachea, which allowed differentiation from esophageal tissue in ex vivo swine, in vivo swine, and human cadavers. The goal of this study is to determine if spectral reflectance can differentiate between trachea and other airway tissues in living humans and whether the unique tracheal spectral profile persists in the presence of an inhalation injury. Reflectance spectra were captured using a custom fiber-optic probe from the buccal mucosa, posterior oropharynx, and trachea of healthy humans intubated for third molar extraction and from the trachea of patients admitted to a burn intensive care unit with and without inhalation injury. Using ratio comparisons, we found that the tracheal spectral profile was significantly different from buccal mucosa or posterior oropharynx, but the area under the curve values are not high enough to be used clinically. In addition, inhalation injury did not significantly alter the spectral reflectance of the trachea. Further studies are needed to determine the utility of this technology in a clinical setting and to develop an algorithm for tissue differentiation.

Systematic Review and Meta-Analysis of Mass Spectrometry Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Schizophrenia.

Mass spectrometry (MS)-based techniques can be a powerful tool to identify neuropsychiatric disorder biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids of schizophrenia (SCZ) patients to identify disease biomarkers and relevant networks of biological pathways. Following PRISMA guidelines, a search was performed for studies that used MS proteomics approaches to identify proteomic differences between SCZ patients and healthy control groups (PROSPERO database: CRD42021274183). Nineteen articles fulfilled the inclusion criteria, allowing the identification of 217 differentially expressed proteins. Gene ontology analysis identified lipid metabolism, complement and coagulation cascades, and immune response as the main enriched biological pathways. Meta-analysis results suggest the upregulation of FCN3 and downregulation of APO1, APOA2, APOC1, and APOC3 in SCZ patients. Despite the proven ability of MS proteomics to characterize SCZ, several confounding factors contribute to the heterogeneity of the findings. In the future, we encourage the scientific community to perform studies with more extensive sampling and validation cohorts, integrating omics with bioinformatics tools to provide additional comprehension of differentially expressed proteins. The produced information could harbor potential proteomic biomarkers of SCZ, contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.