Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Diagnosis, performance and added value of assessing ventricular dyssynchrony by phase analysis in patients with three-vessel disease: A single-center cross-sectional study in Mexico.

BACKGROUND: Three-vessel disease (3VD) is a cardiovascular disorder that affects the three main coronary arteries. Gated myocardial perfusion SPECT (GMPS) evaluates ventricular function, synchrony, and myocardial perfusion. However, the diagnostic performance of GMPS parameters to assess 3VD has not been fully explored. AIMS: To assess the univariate performance capacity of GMPS parameters, and to evaluate whether phase parameters could provide additional predictive value for the detection of patients with 3VD compared to control subjects. METHODS: We designed paired retrospective samples of GMPS images of patients with 3VD (stenosis > 70% of left anterior descending, right coronary, and circumflex coronary arteries) and without 3VD. A GMPS in rest-stress protocol was performed using 99mTc-Sestamibi and thallium and analyzed with the 3D method. Area under the receiver-operating characteristic curves (AUROC), decision curve analyses and diagnostic test performance were obtained for univariable analyses and stepwise binomial logistic regression for multivariable performance. RESULTS: 474 Patients were included: 237 with 3VD (84% males, mean age 61.7 ± 9.9 years) and 237 with normal GMPS (51% women, mean age 63.8 ± 10.6 years). The highest AUROC for perfusion parameters were recorded for SSS, SRS and TID. For dyssynchrony parameters, both entropy and bandwidth in rest and stress phases displayed the highest AUROC and diagnostic capacity to detect 3VD. A multivariate model with SRS ≥ 4, SDS ≥ 2, TID > 1.19 and sBW ≥ 48° displayed the highest diagnostic capacity (0.923 [95% CI 0.897-0.923]) to detect 3VD. CONCLUSION: Perfusion and dyssynchrony were the parameters which were most able to discriminate patients with 3VD from those who did not have CAD.

Microscopic and submicroscopic Plasmodium infections in indigenous and non-indigenous communities in Colombia.

BACKGROUND: The indigenous population is considered a highly susceptible group to malaria because individuals usually live in areas with high exposure to Anopheles and poverty, and have limited access to health services. There is a great diversity of indigenous communities in Colombia living in malaria-endemic areas; however, the burden of infection in these populations has not been studied extensively. This study aimed to determine the prevalence of Plasmodium infections in indigenous and non-indigenous communities in two malaria-endemic areas in Colombia. METHODS: A community-based cross-sectional survey was conducted in seven villages of Turbo and El Bagre municipalities; three of these villages were indigenous communities. Inhabitants of all ages willing to participate were included. Sociodemographic and clinical data were recorded as well as household information. The parasitological diagnosis was performed by microscopy and nested PCR. The prevalence of microscopy and submicroscopic infection was estimated. An adjusted GEE model was used to explore risk factors associated with the infection. RESULTS: Among 713 participants, 60.7% were from indigenous communities. Plasmodium spp. was detected in 30 subjects (4.2%, CI 95% 2.9-5.9); from those, 29 were in the indigenous population, 47% of infections were afebrile, and most of them submicroscopic (10/14). Microscopic and submicroscopic prevalence was 2.5% (CI 95% 1.6-3.9) and 1.7% (CI 95% 0.9-2.9), respectively. In El Bagre, all infections occurred in indigenous participants (3.9%, CI 95% 2.2-7.1), and 81% were submicroscopic. By contrast, in Turbo, the highest prevalence occurred in indigenous people (11.5%; CI 95%: 7.3-17.5), but 88.8% were microscopic. Living in an indigenous population increased the prevalence of infection compared with a non-indigenous population (PR 19.4; CI 95% 2.3-166.7). CONCLUSION: There is a high proportion of Plasmodium infection in indigenous communities. A substantial proportion of asymptomatic and submicroscopic carriers were detected. The identification of these infections, not only in indigenous but also in the non-indigenous population, as well as their associated factors, could help to implement specific malaria strategies for each context.

Quantification of malaria antigens PfHRP2 and pLDH by quantitative suspension array technology in whole blood, dried blood spot and plasma.

BACKGROUND: Malaria diagnostics by rapid diagnostic test (RDT) relies primarily on the qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and Plasmodium spp lactate dehydrogenase (pLDH). As novel RDTs with increased sensitivity are being developed and implemented as point of care diagnostics, highly sensitive laboratory-based assays are needed for evaluating RDT performance. Here, a quantitative suspension array technology (qSAT) was developed, validated and applied for the simultaneous detection of PfHRP2 and pLDH in a variety of biological samples (whole blood, plasma and dried blood spots) from individuals living in different endemic countries. RESULTS: The qSAT was specific for the target antigens, with analytical ranges of 6.8 to 762.8 pg/ml for PfHRP2 and 78.1 to 17076.6 pg/ml for P. falciparum LDH (Pf-LDH). The assay detected Plasmodium vivax LDH (Pv-LDH) at a lower sensitivity than Pf-LDH (analytical range of 1093.20 to 187288.5 pg/ml). Both PfHRP2 and pLDH levels determined using the qSAT showed to positively correlate with parasite densities determined by quantitative PCR (Spearman r = 0.59 and 0.75, respectively) as well as microscopy (Spearman r = 0.40 and 0.75, respectively), suggesting the assay to be a good predictor of parasite density. CONCLUSION: This immunoassay can be used as a reference test for the detection and quantification of PfHRP2 and pLDH, and could serve for external validation of RDT performance, to determine antigen persistence after parasite clearance, as well as a complementary tool to assess malaria burden in endemic settings.

Malaria in Pregnancy in Endemic Regions of Colombia: High Frequency of Asymptomatic and Peri-Urban Infections in Pregnant Women with Malaria.

Background: Malaria in pregnancy (MiP) has been associated with adverse pregnancy outcomes. There is limited information on MiP in low transmission regions as Colombia. This study aimed to describe the epidemiology of MiP through active surveillance of infections by microscopy and polymerase chain reaction (PCR). Methods: A cross-sectional study was conducted between May 2016 and January 2017 in five municipalities (Apartadó, Turbo, El Bagre, Quibdó, and Tumaco) in Colombia. Pregnant women self-presenting at health centers for antenatal care visits, seeking medical care for suspected malaria, or delivery, were enrolled. Diagnosis of Plasmodium spp was made in peripheral and placental blood samples by microscopy and PCR. Results: A total of 787 pregnant women were enrolled; plasmodial infection was diagnosed by microscopy in 4.2% (95% CI 2.8-5.6; 33/787) or by nPCR in 5.3% (95% CI 3.8-6.9; 42/787) in peripheral blood. Most of the infections were caused by P. falciparum (78.5%), and 46% were afebrile (asymptomatic). Women in the first and second trimester of pregnancy were more likely to be infected (aOR = 3.06, 95%CI = 1.6 - 5.8). To live in the urban/peri-urban area (aOR = 3.04, 95%CI = 1.4 - 6.56), to have a history of malaria during last year (aOR = 5.45, 95%IC = 2.16 - 13.75), and the infrequent bed net usage (aOR = 2.8, 95%CI = 1.31 - 5.97) were associated with the infection. Pregnant infected women had a higher risk of anaemia (aOR = 2.18, 95%CI = 1.15 - 4.12) and fever (aOR = 14.2, 95%CI = 6.89 - 29.8). Conclusion: The screening for malaria during antenatal care in endemic areas of Colombia is highly recommended due to the potential adverse effects of Plasmodium spp. infection in pregnancy and as an important activity for the surveillance of asymptomatic infections in the control of malaria.

Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia.

Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies-one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naïve populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk.

Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for screening malaria in peripheral and placental blood samples from pregnant women in Colombia.

BACKGROUND: Pregnant women frequently show low-density Plasmodium infections that require more sensitive methods for accurate diagnosis and early treatment of malaria. This is particularly relevant in low-malaria transmission areas, where intermittent preventive treatment is not recommended. Molecular methods, such as polymerase chain reaction (PCR) are highly sensitive, but require sophisticated equipment and advanced training. Instead, loop mediated isothermal amplification (LAMP) provides an opportunity for molecular detection of malaria infections in remote endemic areas, outside a reference laboratory. The aim of the study is to evaluate the performance of LAMP for the screening of malaria in pregnant women in Colombia. METHODS: This is a nested prospective study that uses data and samples from a larger cross-sectional project conducted from May 2016 to January 2017 in three Colombian endemic areas (El Bagre, Quibdó, and Tumaco). A total of 531 peripheral and placental samples from pregnant women self-presenting at local hospitals for antenatal care visits, at delivery or seeking medical care for suspected malaria were collected. Samples were analysed for Plasmodium parasites by light microscopy (LM), rapid diagnostic test (RDT) and LAMP. Diagnostic accuracy endpoints (sensitivity, specificity, predictive values, and kappa scores) of LM, RDT and LAMP were compared with nested PCR (nPCR) as the reference standard. RESULTS: In peripheral samples, LAMP showed an improved sensitivity (100.0%) when compared with LM 79.5% and RDT 76.9% (p < 0.01), particularly in afebrile women, for which LAMP sensitivity was two-times higher than LM and RDT. Overall agreement among LAMP and nPCR was high (kappa value = 1.0). Specificity was similar in all tests (100%). In placental blood, LAMP evidenced a four-fold improvement in sensitivity (88.9%) when compared with LM and RDT (22.2%), being the only method, together with nPCR, able to detect placental infections in peripheral blood. CONCLUSIONS: LAMP is a simple, rapid and accurate molecular tool for detecting gestational and placental malaria, being able to overcome the limited sensitivity of LM and RDT. These findings could guide maternal health programs in low-transmission settings to integrate LAMP in their surveillance systems for the active detection of low-density infections and asymptomatic malaria cases.

[Genotyping of human papillomavirus in women under 25 years old treated in the screening program for cervical cancer]. / Genotipificación del virus papiloma humano en mujeres bajo 25 años de edad participantes del Programa Nacional del Cáncer Cérvico-uterino en la Región de la Araucanía, Chile.

BACKGROUND: In Chile, cervical cancer (CC) is the second leading cause of death from malignancy in women. The main causal agent of cervical cancer is the human papillomavirus (HPV). This virus is the most common sexually transmitted infection among sexually active youth. An early onset of sexual life increases the chances of HPV infection; this may involve a possible early development of cervical intraepithelial neoplasia and CC, creating a major public health problem. OBJECTIVE: To present HPV frequency in women under the age of 25, treated in the CC screening program and their follow-up after histopathological diagnosis. METHODS: 173 cervical samples were genotyped by polymerase chain reaction and non-radioactive reverse hybridization (line blot). RESULTS: The overall frequency of HPV was 84.8%. HPV16 was the most prevalent. In 12.1% of women the cervical lesion persisted or progressed. 28.9% of women had irregular follow-up; in this group, 88% were HPV(+) and 52% had no record of Pap smear in the past 3 years. DISCUSSION: The results reaffirm the usefulness of complementing the Pap and HPV detection as a primary screening tool in sexually active women. They also suggest the possibility of extending the age coverage of the national screening program.

[Phenotypic variability of cystic fibrosis: case report of twins with F508/F508 mutation]. / Variabilidad fenotípica de la fibrosis quística: reporte de 2 gemelos con la mutación F508/F508.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease caused by a mutation in the CFTR gene, resulting in an alteration of a protein involved in sodium and chloride transport in the apical plasma membrane of epithelial cells in respiratory and intestinal tracts. It primarily presents respiratory compromise, affecting other systems in different ways. Meconium ileus is a gastrointestinal manifestation that occurs in 10-20% of patients, which is not entirely attributable to a specific CFTR mutation. OBJECTIVE: To report a case of monozygotic twins diagnosed with CF (F508) in whom phenotypic variation is evident based on the expression of meconium ileus, showing that there are external modifiers in the development of this complication. CASE REPORT: monoamniotic monochorionic twin pregnancy which resulted in preterm births. One of the patient presented meconium ileus at birth leading to CF suspicion and establishing the diagnosis by (F508/F508) molecular analysis in both twins. CONCLUSION: Phenotypic variability in these twins supports the hypothesis proposed by different authors that there are other gene expression-modulation factors of the disease as well as environmental modifiers that must be taken into account when dealing with this disease.

Alteration of Trophoblast Syncytialization by Plasmodium falciparum-Infected Erythrocytes.

Malaria during pregnancy has been associated with significant risks to both the mother and the fetus, leading to complications such as anemia, low birth weight, and increased infant mortality. The trophoblast cells, a key component of the placenta, are crucial for nutrient and oxygen exchange between mother and fetus. The differentiation of cytotrophoblasts (CTBs) into syncytiotrophoblasts (STBs) is critical for proper pregnancy development. These cells form the bi-stratified epithelium surrounding the placental villi. While previous studies have described an inflammatory activation of STB cells exposed to Plasmodium falciparum-infected erythrocytes (P. falciparum-IE) or components such as hemozoin (HZ), little is known about the direct effect this parasite may have on the epithelial turnover and function of trophoblast cells. This study aims to contribute to understanding mechanisms leading to placental damage during placental malaria using a BeWo cell line as a differentiation model. It was found that P. falciparum-IE interferes with the fusion of BeWo cells, affecting the differentiation process of trophoblast. A reduction in syncytialization could be associated with the adverse effects of infection in fetal health, altering the remodeling of the trophoblast epithelial barrier and reducing their capacity to exchange substances. However, further studies are necessary to assess alterations in the functionality of this epithelium.

Assessment of the Integrity and Function of Human Term Placental Explants in Short-Term Culture.

Human placental explants (HPEs) culture has generated significant interest as a valuable in vitro model for studying tissue functions in response to adverse conditions, such as fluctuations in oxygen levels, nutrient availability, exposure to pathogenic microorganisms, and toxic compounds. HPEs offers the advantage of replicating the intricate microenvironment and cell-to-cell communication involved in this critical and transient organ. Although HPEs culture conditions have been extensively discussed, a protocol for assessing the viability and function of HPEs during short-term culture has not been previously outlined. In this study, we have developed a short-term HPEs culture protocol, specifically up to 72 h, and have employed quantitative, semi-quantitative, and qualitative analyses to evaluate tissue viability and function over time. Under our standardized conditions, placental villi explants began to regain their structural properties (the integrity of the trophoblast and villous stroma) and the functionality of the HPEs (production of angiogenic, endocrine, and immunological factors) starting from 48 h of culture. This restoration ensures a suitable environment for several applications. The data presented here can be highly valuable for laboratories aiming to implement an HPEs model, whether in the process of standardization or seeking to enhance and optimize working conditions and timing with placental tissue.

Induction of pro-inflammatory response of the placental trophoblast by Plasmodium falciparum infected erythrocytes and TNF.

BACKGROUND: Plasmodium falciparum placental malaria is characterized by the sequestration of infected erythrocytes (IEs) in the placental intervillous space via adherence to chondroitin sulphate A (CSA), production of inflammatory molecules, and leukocytes infiltration. Previous reports suggest that the syncytiotrophoblast (ST) immunologically responds to IEs contact. This study explores the inflammatory response induced in BeWo cells by adherence of IEs and TNFstimulation. METHODS: A non-syncitialized BeWo cells (trophoblast model) were used to evaluate its response to CSA-adherents IEs (FCB1csa, FCB2csa, FCR3csa, 3D7csa) and TNF stimulation. Expression of membrane ICAM-1 (mICAM-1) receptor in BeWo cells was quantified by flow cytometry and the IL-8, IL-6 and soluble ICAM-1 (sICAM-1) concentrations were quantified by enzyme-linked immunosorbentassay (ELISA) in BeWo stimulated supernatants. RESULTS: BeWo cells stimulated with TNF and CSA-adherents IEs of FCB1csa and 3D7csa (strains with higher adhesion) increase the expression of ICAM-1 on the surface of cells and the secretion of immune factors IL-8, IL-6 and sICAM-1. This inflammatory response appears to be related to the level of adherence of IEs because less adherent strains do not induce significant changes. CONCLUSIONS: It was found that BeWo cells responds to CSA-IEs and to TNF favouring a placental pro-inflammatory environment, evidenced by increases in the expression of membrane mICAM-1 and release of soluble ICAM-1, as well as the IL-8 and IL-6 secretion. The expression of ICAM-1 in BeWo cells might be associated to an increase in leukocyte adhesion to the trophoblast barrier, promoting greater inflammation, while the sICAM-1 release could be a protection mechanism activated by trophoblastic cells, in order to regulate the local inflammatory response.

How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.

Alteraciones en el nervio óptico y retina en pacientes con COVID-19. Una revisión teórica.

The objective of this research is to identify and systematize the medical conditions generated by SARS-CoV-2 on the optic nerve and retina of young, adult, and elderly adults who suffered from COVID-19 in the period 2019-2022. A theoretical documentary review (TDR) was conducted within the framework of an investigation to determine the current state of knowledge of the subject under study. The TDR includes the analysis of publications in the scientific databases PubMed/Medline, Ebsco, Scielo and Google. A total of 167 articles were found, of which 56 were studied in depth, and these evidence the impact of COVID-19 infection on the retina and optic nerve of infected patients, both during the acute phase and in subsequent recovery. Among the reported findings, the following stand out: anterior and posterior non-arteritic ischemic optic neuropathy, optic neuritis, central or branch vascular occlusion, paracentral acute medial maculopathy, neuroretinitis, as well as concomitant diagnoses such as possible Vogt-Koyanagi-Harada disease, multiple evanescent white dot syndrome (MEWDS), Purtscher-like retinopathy, among others.

Exploring the microbiome of two uterine sites in cows.

Bacterial communities in the mammalian reproductive system can be rich and diverse, differing in structure and quantity depending on location. In addition, its microbiome is associated with the state of health of this tract and reproductive success. This study evaluated the microbiome composition of the uterine body (UB) and uterine horn mucosa (UH) samples using 16S rRNA sequencing of samples extracted from cows in the Amazon region. It was observed that four main phyla were shared between the uterine sites: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Linear discriminant analysis effect size and heat tree analysis showed that members of Lachnospiraceae (NK3A20 group) and Oscillospiraceae were significantly more abundant in the UB than in UH. In addition, there are more unique genera in the UB than in the UH. A higher bacterial load in UB than in UH is expected because of the exposure to external factors of UB. However, comparing the site's communities through beta diversity did not generate well-defined clustering. Thus, it can be attributed to the closeness of the sites, which would make the niches similar ecologically and microbiologically. Therefore, this research provides knowledge to understand biomarkers in the prior reproduction period.

Psychiatric disorders after pediatric traumatic brain injury: a prospective, longitudinal, controlled study.

The objective was to examine the effects of traumatic brain injury (TBI), as compared with orthopedic injury (OI), relative to the risk for psychiatric disorder. There has only been one previous prospective study of this nature. Participants were age 7-17 years at the time of hospitalization for either TBI (complicated mild-to-severe) or OI. The study used a prospective, longitudinal, controlled design, with standardized psychiatric assessments conducted at baseline (reflecting pre-injury functioning) and 3 months post-injury. Assessments of pre-injury psychiatric, adaptive functioning, family adversity, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales. The outcome measure was the presence of a psychiatric disorder not present before the injury ("novel"), during the first 3 months after TBI. Enrolled participants (N=141) included children with TBI (N=75) and with OI (N=66). The analyses focused on 118 children (84%) (TBI: N=65; OI: N=53) who returned for follow-up assessment at 3 months. Novel psychiatric disorder (NPD) occurred significantly more frequently in the TBI (32/65; 49%) than the OI (7/53; 13%) group. This difference was not accounted for by pre-injury lifetime psychiatric status; pre-injury adaptive functioning; pre-injury family adversity, family psychiatric history, socioeconomic status, injury severity, or age at injury. Furthermore, none of these variables significantly discriminated between children with TBI who developed, versus those who did not develop, NPD. These findings suggest that children with complicated mild-to-severe TBI are at significantly higher risk than OI-controls for the development of NPD in the first 3 months after injury.

Uveitic Glaucoma and Hansen's disease, A case report.

BACKGROUND: The number of Hansen's disease cases in Latin America and the Caribbean has decreased in the last decade; nevertheless, the region is still struggling with infections caused by Mycobacterium leprae. This is a case report that portrays the diagnostic and management challenges associated with atypical uveitic glaucoma that is due to Hansen's disease. CASE PRESENTATION: A 62-year-old female was referred with a 2-year history of anterior uveitis of unknown etiology and ocular hypertension. Past medical history and general physical examination were unremarkable. Upon ocular examination, her best-corrected visual acuity (BCVA) was 20/25 in the OD and 20/60 in the OS. Tonometry showed intraocular pressures (IOPs) of 29 mmHg and 22 mmHg in her right and left eyes, respectively. The slit-lamp examination showed clinical signs of bilateral granulomatous anterior uveitis and cataracts; gonioscopy revealed open angles with some peripheral anterior synechiae for both eyes. Fundus examination and glaucoma tests revealed mild glaucomatous damage in the right eye. Given the presentation of uveitis, the respective questionnaire was completed by internal medicine and rheumatology. Four months later, after bilateral cataract surgery, the patient developed skin plaques on the face, neck, upper back, and extremities, which were biopsied and identified as positive for tuberculoid leprosy. CONCLUSION: This is the first case report in Ecuador of atypical glaucoma triggered by infectious uveitis produced by Mycobacterium leprae. We describe a female patient's clinical presentation with several ocular signs of leprosy and other nonspecific and rarely seen symptoms. Uveitis is a condition that often requires a multidisciplinary team of ophthalmologists and clinicians because of the possible manifestation of an underlying systemic disease, creating a challenge for all the medical personnel involved in the management of the case.

Case report: Infrequent littoral cell angioma of the spleen.

INTRODUCTION AND IMPORTANCE: Littoral cell angioma is a rare solid spleen tumor with uncertain malignant potential. It is usually asymptomatic; therefore, its diagnosis is usually incidental. There are approximately 150 cases reported in the medical literature, but none of them in the Hispanic population. CASE PRESENTATION: We present a case of a 54-year-old woman who presented to our clinic with nonspecific abdominal pain. Imaging studies show a splenic mass with littoral cell angioma characteristics. The patient underwent an open splenectomy with subsequent histopathologic and immunohistochemical studies that confirmed the presence of a littoral cell angioma of a diameter of 8 × 4.5 × 3.5 cm. The patient was discharged after an uneventful postoperative recovery and was referred to the outpatient clinic for follow up. CLINICAL DISCUSSION: This case report highlights the close relationship between the littoral cell angioma, neoplasias, and autoimmune diseases. Even though LCA has a good prognosis, there is still the possibility of malignant transformation, especially when the spleen weighs 1500 g; our patient's sample pointed towards a benign pathology. LCA has a positive IHC for endothelial and histiocyte tissues. The IHC results of our patient were positive for CD34+ and CD68+, confirming the LCA diagnosis. CONCLUSION: Within red pulp spleen tumors, LCA should be highly considered as a differential diagnosis in all types of populations. In the case of a confirmed LCA, routine screening for neoplasias and autoimmune diseases should be performed.

Association of variants in IL1B, TLR9, TREM1, IL10RA, and CD3G and Native American ancestry on malaria susceptibility in Colombian populations.

Host genetics is an influencing factor in the manifestation of infectious diseases. In this study, the association of mild malaria with 28 variants in 16 genes previously reported in other populations and/or close to ancestry-informative markers (AIMs) selected was evaluated in an admixed 736 Colombian population sample. Additionally, the effect of genetic ancestry on phenotype expression was explored. For this purpose, the ancestral genetic composition of Turbo and El Bagre was determined. A higher Native American ancestry trend was found in the population with lower malaria susceptibility [odds ratio (OR) = 0.416, 95% confidence interval (95% CI) = 0.234-0.740, P = 0.003]. Three AIMs presented significant associations with the disease phenotype (MID1752, MID921, and MID1586). The first two were associated with greater malaria susceptibility (D/D, OR = 2.23, 95% CI = 1.06-4.69, P = 0.032 and I/D-I/I, OR = 2.14, 95% CI = 1.18-3.87, P = 0.011, respectively), and the latter has a protective effect on the appearance of malaria (I/I, OR = 0.18, 95% CI = 0.08-0.40, P < 0.0001). After adjustment by age, sex, municipality, and genetic ancestry, genotype association analysis showed evidence of association with malaria susceptibility for variants in or near IL1B, TLR9, TREM1, IL10RA, and CD3G genes: rs1143629-IL1B (G/A-A/A, OR = 0.41, 95% CI = 0.21-0.78, P = 0.0051), rs352139-TLR9 (T/T, OR = 0.28, 95% CI = 0.11-0.72, P = 0.0053), rs352140-TLR9 (C/C, OR = 0.41, 95% CI = 0.20-0.87, P = 0.019), rs2234237-TREM1 (T/A-A/A, OR = 0.43, 95% CI = 0.23-0.79, P = 0.0056), rs4252246-IL10RA (C/A-A/A, OR = 2.11, 95% CI = 1.18-3.75, P = 0.01), and rs1561966-CD3G (A/A, OR = 0.20, 95% CI = 0.06-0.69, P = 0.0058). The results showed the participation of genes involved in immunological processes and suggested an effect of ancestral genetic composition over the traits analyzed. Compared to the paisa population (Antioquia), Turbo and El Bagre showed a strong decrease in European ancestry and an increase in African and Native American ancestries. Also, a novel association of two single nucleotide polymorphisms with malaria susceptibility was identified in this study.