Neurodevelopment in preschool children exposed and unexposed to Zika virus in utero in Nicaragua: a prospective cohort study.

BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Cytogenetic damage by vanadium(IV) and vanadium(III) on the bone marrow of mice.

Vanadium is a strategic metal that has many important industrial applications and is generated by the use of burning fossil fuels, which inevitably leads to their release into the environment, mainly in the form of oxides. The wastes generated by their use represent a major health hazard. Furthermore, it has attracted attention because several genotoxicity studies have shown that some vanadium compounds can affect DNA; among the most studied compounds is vanadium pentoxide, but studies in vivo with oxidation states IV and III are scarce and controversial. In this study, the genotoxic and cytotoxic potential of vanadium oxides was investigated in mouse bone marrow cells using structural chromosomal aberration (SCA) and mitotic index (MI) test systems. Three groups were administered vanadium(IV) tetraoxide (V2O4) intraperitoneally at 4.7, 9.4 or 18.8 mg/kg, and three groups were administered vanadium(III) trioxide (V2O3) at 4.22, 8.46 or 16.93 mg/kg body weight. The control group was treated with sterile water, and the positive control group was treated with cadmium(II) chloride (CdCl2). After 24 h, all doses of vanadium compounds increased the percentage of cells with SCA and decreased the MI. Our results demonstrated that under the present experimental conditions and doses, treatment with V2O4 and V2O3 induces chromosomal aberrations and alters cell division in the bone marrow of mice.

Temephos, an organophosphate larvicide for residential use: a review of its toxicity.

Temephos (O,O,O',O'-tetramethyl O,O'-thiodi-p-phenylene bis(phosphorothioate)) is a larvicide belonging to the family of organophosphate pesticides used for the control of different vectors of diseases, such as dengue, Zika, chikungunya, and dracunculiasis. The aim of this review was to discuss the available published information about temephos toxicokinetics and toxicity in mammals. Temephos is quickly absorbed in the gastrointestinal tract, distributed to all organs, and then it accumulates mainly in adipose tissue. It is metabolized by S-oxidation, oxidative desulfuration, and hydrolysis reactions, with the possible participation of cytochrome P450 (CYP). Temephos is mainly eliminated by feces, whereas some of its metabolites are eliminated by urine. The World Health Organization classifies it as class III: slightly dangerous with a NOAEL (no-observed adverse effect level) of 2.3 mg/kg/day for up to 90 days in rats, based on brain acetylcholinesterase (AChE) inhibition. A LOAEL (lowest observable adverse effect level) of 100 mg/kg/day for up to 44 days in rats was proposed based on cholinergic symptoms. However, some studies have shown that temephos causes toxic effects in mammals. The inhibition of the enzyme acetylcholinesterase (AChE) is one of its main demonstrated effects; however, this larvicide has also shown genotoxic effects and some adverse effects on male reproduction and fertility, as well as liver damage, even at low doses. We performed an extensive review through several databases of the literature about temephos toxicokinetics, and we recommend to revisit current assessment of temephos with the new available data.

Vanadium(IV) oxide affects embryonic development in mice.

Vanadium(V) and vanadium(IV) are the predominant redox forms present in the environment, and epidemiological studies have reported that prenatal vanadium exposure is associated with restricted fetal growth and adverse birth outcomes. However, data about the toxic effects of vanadium(IV) oxide (V2 O4 ) on the development of mammals are still limited. Therefore, in this work, 4.7, 9.4, or 18.7 mg/kg body weight/injection/day V2 O4 was administered through an intraperitoneal (ip) injection to pregnant mice from gestational days 6 to 16. The results showed that V2 O4 produced maternal and embryo-fetal toxicity and external abnormalities in the offspring, such as malrotated and malpositioned hind limbs, hematomas and head injuries. Moreover, the skeletons of the fetuses presented reduced ossification of the cranial bones, including the frontal and parietal bones, corresponding to head injuries observed in the external assessment of the fetuses. These results demonstrate that administration of V2 O4 to pregnant females in the organogenesis period adversely affects embryonic development.

Atraumatic osteonecrosis of the humeral head: pathophysiology and current concepts of evaluation and treatment.

The humeral head is considered the second most common site for osteonecrosis to occur after the femoral head. As seen in the femoral head, the circulatory implications characteristic of this condition are attributable to the interaction between a genetic predisposition and the exposure to certain risk factors. There is no consensus regarding the pathogenesis of osteonecrosis, yet the final common pathway results in disrupted blood supply, increased intraosseous pressure, and bone death. Disease staging using radiography and magnetic resonance imaging is predictive of disease progression and can help the orthopedic surgeon to guide treatment. Although there is a myriad of treatment modalities, there is a lack of high-quality evidence to conclude what is the most appropriate treatment option for each stage of humeral head osteonecrosis. Nonoperative treatment is the preferred option in early-stage disease, and it may prevent disease progression. Nonetheless, in some cases, disease progression occurs despite nonoperative measures, and surgical treatment is required. The purpose of this article is to provide an updated review of the available evidence on risk factors, diagnosis, and treatment of atraumatic humeral head osteonecrosis.

Capecitabine induced fingerprint loss: Case report and review of the literature.

INTRODUCTION: Adermatoglyphia is defined as the medical condition clinically diagnosed to those who have a congenital or acquired loss of the epidermal ridges on the fingertips, commonly known as fingerprints. Capecitabine, a fluoropyrimidine, is the treatment of choice in a myriad of tumors and has occasionally been reported to cause adermatoglyphia as a secondary effect upon its use. CASE REPORT: A 52-year-old female patient, diagnosed with stage IV metastatic left breast cancer with extension to bone in late 2011 reported upon biopsy a hormone receptor positive Her2 negative ductal carcinoma. After initial treatment with a combined radiotherapy and chemotherapy palliative treatment, hepatic and lung metastasis progression obliged capecitabine oral intake. In 2018, after two years on the fluoropyrimidine (capecitabine), the patient reported adermatoglyphia. MANAGEMENT & OUTCOME: The patient opted to continue taking the medication, since such treatment was working with no other meaningful side effects. Her last work-up studies continue to show complete lung and liver response with stable bone disease. DISCUSSION: Capecitabine is a common drug in the therapy against metastatic breast cancer due to its manageable safety profile. Hand-foot syndrome is a frequent side effect caused by this drug, with dosage adjustment recommended with progression of symptoms. Recent publications have reported adermatoglyphia as a rare side effect of capecitabine use. Upon further examination through dermatoscopy and biopsy, the patient was evidenced to have lost the epidermal ridges that form fingerprints. A score of 9 on the Naranjo scale confirmed to be a consequence of the administration of capecitabine.

Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term.

Dengue virus serotypes 1 to 4 (DENV1­4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence after the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme-linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Unexpectedly, we found that overall DENV iELISA titers stabilized by 8 months after primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies after ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer set point, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

A rare cause of headache and fever in a healthy woman / Una rara causa de cefalea y fiebre en una mujer sana

Abstract Cryptococcocis is a fungal infection that primarily affects immunocompromised hosts; disseminated infection is uncommon in immunocompetent patients. We describe a case of a previously healthy woman without risk factors, who was admitted to the emergency department with headache, fever and altered mental status. As a result, a cryptococcal disseminated infection was diagnosed.

Resumen La criptococosis es una infección por hongos que afecta principalmente a huéspedes inmunodeprimidos; la infección diseminada es infrecuente en pacientes inmunocompetentes. Reportamos el caso de una mujer previamente sana, sin factores de riesgo, ingresada a urgencias por cefalea, fiebre y alteración del estado mental quien posteriormente fue diagnosticada con criptococosis diseminada.

Genotoxicity and cytotoxicity evaluation of two thallium compounds using the Drosophila wing somatic mutation and recombination test.

Thallium (Tl) is a heavy and toxic metal and a byproduct of several human activities, such as cement production, mining, and coal combustion. Thallium is found in fruits, vegetables, and animal fodder with high Tl contamination; therefore, it is an environmental pollution issue and a toxicological contamination problem for human beings and other organisms when exposed to it. The mutagenic potential of Tl and its compounds is controversial, and there are few in vivo studies on its effects. We conducted the animal bioassay Drosophila wing somatic mutation and recombination test (SMART) to test for genotoxicity and assessed the genotoxic effects of Tl acetate (TlCH3COO) and Tl sulfate (Tl2SO4) on Drosophila melanogaster. Third instar larvae from the SMART standard cross (ST) were fed Tl acetate [0.2, 2, 20, 200, 600 and 1200 µM] and Tl sulfate [0.2, 2, 20, 200, and 600 µM]. Hexavalent chromium [CrO3, 500 µM] served as the positive control, and Milli-Q water served as the negative control. Only the high Tl2SO4 [600 µM] concentration resulted in genotoxicity with 87.6% somatic recombination, and both salts disrupted cell division of wing imaginal disc cells, showing the expected cytotoxic effects. Genotoxic risks due to high metal levels by bioaccumulation of Tl+1 or its compounds require further evaluation with other in vivo and in vitro assays.

Síndrome de la bolsa de orina púrpura / Purple urine bag syndrome

Resumen El síndrome de la bolsa de orina púrpura es una condición clínica de prevalencia desconocida en Colombia debido al escaso reporte de casos a nivel nacional. Esta entidad se presenta exclusivamente en pacientes portadores de sonda vesical con factores de riesgo asociados como enfermedad renal crónica, patologías neurológicas, residentes de hogares geriátricos, sexo femenino, entre otros. La coloración púrpura de la orina se da en un ambiente urinario alcalino propiciado por bacterias específicas, en donde se genera una reacción de oxidación del indoxil sulfato en índigo e indirrubina por acción de las enzimas fosfatasas/sulfatasas de estos microorganismos, dichos pigmentos se mezclan generando la coloración púrpura en la bolsa urinaria. Se reporta el caso de un paciente masculino de 75 años con un cuadro clásico de síndrome de la bolsa urinaria púrpura, con el propósito de ampliar el conocimiento en la literatura nacional vigente. Adicionalmente, con esta publicación se busca que los profesionales de la salud comprendan los mecanismos fisiopatológicos por los cuales se produce esta entidad para saber abordarla apropiadamente.

Abstract Purple urine bag syndrome is a rare clinical condition, of unknown prevalence, with few reports published in our country that presents exclusively in catheterized patients with multiple risk factors, such as chronic kidney disease, neurological pathologies, residents of nursing homes and affects more females than males. The purple discoloration of urine is generated by indoxyl-sulfate degradation to indigo and indirubin lead by phosphatases/sulphatases enzymes produced by specific bacteria, associated to an alkaline urine environment, those two pigments combine which turns to purple discoloration appreciated in the urinary bag and catheter. The present case report is about a 75-year-old male, which appears with a classic clinical presentation. This case report has the objective, for health care workers, to remember the importance of basic care of urinary catheters, understand the underlying physiopathology and in consequence improve patient care.

Vanadium oxides modify the expression levels of the p21, p53, and Cdc25C proteins in human lymphocytes treated in vitro.

In vitro assays have demonstrated that vanadium compounds interact with biological molecules similar to protein kinases and phosphatases and have also shown that vanadium oxides decrease the proliferation of cells, including human lymphocytes; however, the mechanism, the phase in which the cell cycle is delayed and the proteins involved in this process are unknown. Therefore, we evaluated the effects of vanadium oxides (V2 O3 , V2 O4 and V2 O5 ) in human lymphocyte cultures (concentrations of 2, 4, 8, or 16 µg/ml) on cellular proliferation and the levels of the p53, p21 and Cdc25C proteins. After 24 h of treatment with the different concentrations of vanadium oxides, the cell cycle phases were determined by evaluating the DNA content using flow cytometry, and the levels of the p21, p53 and Cdc25C proteins were assessed by Western blot analysis. The results revealed that the DNA content remained unchanged in every phase of the cell cycle; however, only at high concentrations did protein levels increase. Although, according to previous reports, vanadium oxides induce a delay in proliferation, DNA analysis did not show this occurring in a specific cell cycle phase. Nevertheless, the increases in p53 protein levels may cause this delay.

Development of a risk indicator score for the identification of interstitial lung disease in patients with rheumatoid arthritis / Desarrollo de una regla de predicción clínica para identificar enfermedad pulmonar intersticial en pacientes con artritis reumatoidea

Background: Clinically evident interstitial lung disease (ILD) affects 10%–42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. Methods: Case–control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. Results: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79–0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. Conclusion: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.(AU)

Introducción: La enfermedad pulmonar intersticial (EPI) clínicamente evidente afecta al 10-42% de los pacientes con Artritis Reumatoidea (AR), con impacto en el pronóstico. El objetivo de este estudio fue identificar factores asociados y desarrollar una regla para estratificar el riesgo de EPI en pacientes con AR. Métodos: Estudio de casos y controles. Se incluyeron pacientes con AR de una clínica de enfermedades intersticiales y un servicio de reumatología. Se consignaron datos demográficos, manifestaciones extraarticulares, scores de actividad de la enfermedad, autoanticuerpos, tratamiento. Se analizó con regresión logística multivariada. Resultados: Se incluyeron 118 pacientes con AR, 52 (44%) con EPI (casos) y 66 (56%) sin EPI (controles). Veintiséis (22%) hombres, media de edad 56±15.6 años. Cinco variables se asociaron significativamente con la presencia de EPI: género masculino, tabaquismo, manifestaciones extraarticulares, CDAI> 28, y eritrosedimentación> 80mm/h. El área bajo la curva del modelo final fue 0.86 (IC 95% 0.79-0.92). Se escogieron dos potenciales puntos de corte del score: 2 puntos con una sensibilidad del 90.38% y una especificidad del 63.64%, y 4 puntos con una sensibilidad del 51.9% y una especificidad del 90.9%. Conclusión: Nuestro estudio identificó variables que podrían ayudar a identificar que pacientes con AR se encuentran en riesgo de presentar EPI.(AU)

Development of a risk indicator score for the identification of interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND: Clinically evident interstitial lung disease (ILD) affects 10%-42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. METHODS: Case-control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79-0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. CONCLUSION: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.

Regenerated Silk Fibers Obtained by Straining Flow Spinning for Guiding Axonal Elongation in Primary Cortical Neurons.

The recovery of injured nervous tissue, one of the main goals for regenerative therapeutic approaches, is often hindered by the limited axonal regeneration ability of the central nervous system (CNS). In this regard, the identification of scaffolds that support the reconstruction of functional neuronal tissues and guide the alignment of regenerating neurons is a major challenge in tissue engineering. Ideally, the usage of such scaffolds would promote and guide the axonal growth, a crucial phase for the restoration of neuronal connections and, consequently, the nerve function. Among the materials proposed as scaffolds for CNS regeneration, silk has been used to exploit its outstanding features as a biomaterial to promote axonal regeneration. In this study, we explore, for the first time, the possibility of using high-performance regenerated silk fibers obtained by straining flow spinning (SFS) to serve as scaffolds for inducing and guiding the axonal growth. It is shown that SFS fibers promote the spontaneous organization of dissociated cortical primary cells into highly interconnected cellular spheroid-like tissue formations. Neuronal projections (i.e., axons) from these cellular spheroids span hundreds of microns along the SFS fibers that act as guides and allow the connection of distant spheroids. In addition, it is also shown that SFS fibers serve as scaffolds for neuronal migration covering short and long distances. As a consequence, the usage of high-performance SFS fibers appears as a promising basis for the development of novel therapies, leading to directed axonal regeneration.

Effectiveness of a prevention program in the incidence of cardiovascular outcomes in a low-income population from Colombia: a real-world propensity score-matched cohort study.

BACKGROUND: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are among the leading cause of morbidity and mortality in low-and-middle-income countries (LMICs) but evidence in these contexts regarding the effectiveness of primary prevention interventions taking into account patient adherence is scarce. We aimed to evaluate the effectiveness of a cardiovascular risk management program (De Todo Corazón - DTC program) in the incidence of the first cardiovascular outcome (CVO) in a low-income population from the Caribbean region of Colombia using adherence as the main variable of exposure. METHODS: A retrospective propensity score-matched cohort study was conducted. Adult patients with a diagnosis of hypertension (HTA), diabetes mellitus (DM), chronic kidney disease (CKD), or dyslipidemia affiliated to the DTC program between 2013 and 2018 were considered as the study population. Patients with 30 to 76 years, without a history of CVOs, and with more than 6 months of exposure to the program were included. The main outcome of interest was the reduction in the risk of CVOs (stroke, myocardial infarction, or congestive heart failure) based on the adherence to the intervention (attendance to medical appointments with health care professionals and the control of cardiovascular risk factors). Kaplan Meier curves and propensity score-matched Cox regression models were used to evaluate the association between adherence and the incidence of CVOs. RESULTS: A total of 52,507 patients were included. After propensity score matching, a sample of 35,574 patients was analyzed. Mean (SD) exposure time was 1.97 (0.92) years. Being adherent to the program was associated to a 85.4, 71.9, 32.4 and 78.9% risk reduction of in the low (HR 0.14; 95% CI 0.05-0.37; p < 0.001), medium (HR 0.28; 95% CI 0.21-0.36; p < 0.001), high-risk with DM (HR 0.67; 95% CI 0.43-1.04; p = 0.075) and hig-risk without DM (HR 0.21; 95% CI 0.09-0.48; p < 0.001) categories, respectively. CONCLUSIONS: The DTC program is effective in the reduction of the risk of CVOs. Population-based interventions may be an important strategy for the prevention of CVOs in underserved populations in the context of LMICs. A more exhaustive emphasis on the control of diabetes mellitus should be considered in these strategies.

Zika virus infection enhances future risk of severe dengue disease.

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

The challenging diagnosis of overlapping oral primary/secondary syphilis with nonreactive serology.

The prevalence of oral syphilis, known as "the great imitator" because of its diagnostic complexity and varied clinical manifestations, is increasing worldwide, particularly in people living with HIV (PLWH), who could present false-negative serological results. Although some studies have described the variable presentation of oral syphilis in the context of HIV infection, the difficulty in distinguishing between the primary and secondary stages, clinically and histopathologically, underscores the need to describe atypical cases. We report the case of a 28-year-old HIV-positive man presenting with a 3-month history of painless white/red ulcerated lesion on the soft palate. Physical examination revealed an ulcerated lesion with local signs of inflammation. Initial biopsy revealed a nonspecific inflammatory process and immunohistochemistry (IHC) using anti-Treponema pallidum antibodies showed negative results. The results of serological tests for syphilis (Venereal Disease Research Laboratory and fluorescent treponemal antibody-absorption test) were negative on repeated occasions. Nonetheless, polymerase chain reaction (PCR) assay and subsequent IHC for T. pallidum showed positive results, confirming the diagnosis of oral syphilis. This case illustrates that the diagnosis of oral syphilis is challenging in the absence of serological evidence, and specific tests such as PCR and IHC are useful complementary diagnostic tools.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Clinical and epidemiological characteristics of patients diagnosed with covid-19 in a tertiary care center in Mexico City: a prospective cohort study

ABSTRACT Background: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. Objective: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). Methods: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. Results: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. Conclusions: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.