Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Generalized pustular psoriasis triggered by Zika virus infection.

Zika virus is an emerging arbovirus, which is expanding in epidemic proportions through tropical and subtropical areas of the world. Although Zika is linked to a number of congenital and neurological complications, there is scarce knowledge on the impact of ZIKV infection in human skin. We report the case of a 68-year old woman who presented with generalized pustular psoriasis after a preceding and otherwise uneventful episode of ZIKV infection. Based on recent experimental data on the biology of ZIKV infection in the cutaneous environment, we speculate that ZIKV may have directly triggered the development of generalized pustular psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a polyfunctional T-cell driven immune reaction in the cutaneous milieu.

Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model.

Synthetic cannabinoids (SCs) represent an emerging class of abused drugs associated with psychiatric complications and other substantial health risks. These ligands are largely sold over the internet for human consumption, presumably because of their high cannabinoid 1 receptor (CB1R) affinity and their potency in eliciting pharmacological effects similar to Δ9-tetrahydrocannabinol (THC), as well as circumventing laws illegalizing this plant. Factors potentially contributing to the increased prevalence of SC abuse and related hospitalizations, such as increased CB1R efficacy and non-CB1R targets, highlight the need for quantitative pharmacological analyses to determine receptor mediation of the pharmacological effects of cannabinoids. Accordingly, the present study used pA2 and pKB analyses for quantitative determination of CB1R mediation in which we utilized the CB1R-selective inverse agonist/antagonist rimonabant to elicit rightward shifts in the dose-response curves of five SCs (i.e., A-834,735D; WIN55,212-2; CP55,950; JWH-073; and CP47,497) and THC in producing common cannabimimetic effects (i.e., catalepsy, antinociception, and hypothermia). The results revealed overall similarity of pA2 and pKB values for these compounds and suggest that CB1Rs, and not other pharmacological targets, largely mediated the central pharmacological effects of SCs. More generally, affinity estimation offers a powerful pharmacological approach to assess potential receptor heterogeneity subserving in vivo pharmacological effects of SCs.

Stratification of Cannabinoid 1 Receptor (CB1R) Agonist Efficacy: Manipulation of CB1R Density through Use of Transgenic Mice Reveals Congruence between In Vivo and In Vitro Assays.

Synthetic cannabinoids (SCs) are an emerging class of abused drugs that differ from each other and the phytocannabinoid ∆9-tetrahydrocannabinol (THC) in their safety and cannabinoid-1 receptor (CB1R) pharmacology. As efficacy represents a critical parameter to understanding drug action, the present study investigated this metric by assessing in vivo and in vitro actions of THC, two well-characterized SCs (WIN55,212-2 and CP55,940), and three abused SCs (JWH-073, CP47,497, and A-834,735-D) in CB1 (+/+), (+/-), and (-/-) mice. All drugs produced maximal cannabimimetic in vivo effects (catalepsy, hypothermia, antinociception) in CB1 (+/+) mice, but these actions were essentially eliminated in CB1 (-/-) mice, indicating a CB1R mechanism of action. CB1R efficacy was inferred by comparing potencies between CB1 (+/+) and (+/-) mice [+/+ ED50 /+/- ED50], the latter of which has a 50% reduction of CB1Rs (i.e., decreased receptor reserve). Notably, CB1 (+/-) mice displayed profound rightward and downward shifts in the antinociception and hypothermia dose-response curves of low-efficacy compared with high-efficacy cannabinoids. In vitro efficacy, quantified using agonist-stimulated [35S]GTPγS binding in spinal cord tissue, significantly correlated with the relative efficacies of antinociception (r = 0.87) and hypothermia (r = 0.94) in CB1 (+/-) mice relative to CB1 (+/+) mice. Conversely, drug potencies for cataleptic effects did not differ between these genotypes and did not correlate with the in vitro efficacy measure. These results suggest that evaluation of antinociception and hypothermia in CB1 transgenic mice offers a useful in vivo approach to determine CB1R selectivity and efficacy of emerging SCs, which shows strong congruence with in vitro efficacy.

Agricultural activity shapes the communication and migration patterns in Senegal.

The communication and migration patterns of a country are shaped by its socioeconomic processes. The economy of Senegal is predominantly rural, as agriculture employs over 70% of the labor force. In this paper, we use mobile phone records to explore the impact of agricultural activity on the communication and mobility patterns of the inhabitants of Senegal. We find two peaks of phone calls activity emerging during the growing season. Moreover, during the harvest period, we detect an increase in the migration flows throughout the country. However, religious holidays also shape the mobility patterns of the Senegalese people. Hence, in the light of our results, agricultural activity and religious holidays are the primary drivers of mobility inside the country.

How many patients with post-chikungunya chronic inflammatory rheumatism can we expect in the new endemic areas of Latin America?

Post-chikungunya chronic inflammatory rheumatism (pCHIK-CIR) is one of the consequences that are impacting new endemic countries, such as those in the Americas. The relative frequency of pCHIK-CIR is highly variable, ranging from 14.4 % to 87.2 % (including variable number of patients and follow-up times). Based on those non-weighted values, it is difficult to estimate which would be the expected number of patients with CHIK who will develop CIR. For these reasons, we modeled weighted estimations based on pooled data extracted from those eight representative studies in order to provide cumulative proportion of pCHIK-CIR over time and median time of it, but also estimations of the number of patients with CHIK reported in Latin American countries (within a 95 % CI). This model estimated a prevalence of 47.57 % for pCHIK-CIR (95 % CI 45.08-50.13), with a median time to 50 % of pCHIK-CIR in 20.12 months. Given the reported number of patients with acute CHIK during 2014 in the Americas, our estimates suggest that from those patients, 385,835-429,058 patients will develop pCHIK-CIR. Despite the limitations of these estimates, the provided figures of pCHIK-CIR presented here are preliminary approximations of what the future burden of related rheumatic disease in the region as a consequence of CHIK infection for 2015-2016 could be, given the timeframe of median time of occurrence.

Measuring political polarization: Twitter shows the two sides of Venezuela.

We say that a population is perfectly polarized when divided in two groups of the same size and opposite opinions. In this paper, we propose a methodology to study and measure the emergence of polarization from social interactions. We begin by proposing a model to estimate opinions in which a minority of influential individuals propagate their opinions through a social network. The result of the model is an opinion probability density function. Next, we propose an index to quantify the extent to which the resulting distribution is polarized. Finally, we apply the proposed methodology to a Twitter conversation about the late Venezuelan president, Hugo Chávez, finding a good agreement between our results and offline data. Hence, we show that our methodology can detect different degrees of polarization, depending on the structure of the network.

Secondary hemophagocytic lymphohistiocytosis in zoonoses. A systematic review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that is often fatal despite treatment. It is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of histiocytes with uncontrolled hemophagocytosis and cytokines overproduction. The syndrome is characterized by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinemia. HLH can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections. AIM: To focus on secondary HLH complicating zoonotic diseases. MATERIALS AND METHODS: PubMed search of human cases of HLH occurring during zoonotic diseases was performed combining the terms (haemophagocytic or haemophagocytosis or hemophagocytosis or hemophagocytic or erythrophagocytosis or macrophage activation syndrome) with each one of the etiological agents of zoonoses. RESULTS: Among bacterial diseases, most papers reported cases occurring during brucellosis, rickettsial diseases and Q fever. Regarding viral diseases, most of the cases were reported in patients with avian influenza A subtype H5N1. Among the protozoan zoonoses, most of the cases were reported in patients with visceral leishmaniasis. Regarding zoonotic fungi, most of the cases were reported in AIDS patient with histoplasmosis. No cases of secondary HLH were reported in patient with zoonotic helminthes. CONCLUSIONS: Zoonotic diseases are an important cause of HLH. Secondary HLH can delay the correct diagnosis of the zoonotic disease, and can contribute to an adverse outcome.

Characterizing and modeling an electoral campaign in the context of Twitter: 2011 Spanish Presidential election as a case study.

Transmitting messages in the most efficient way as possible has always been one of politicians' main concerns during electoral processes. Due to the rapidly growing number of users, online social networks have become ideal platforms for politicians to interact with their potential voters. Exploiting the available potential of these tools to maximize their influence over voters is one of politicians' actual challenges. To step in this direction, we have analyzed the user activity in the online social network Twitter, during the 2011 Spanish Presidential electoral process, and found that such activity is correlated with the election results. We introduce a new measure to study political sentiment in Twitter, which we call the relative support. We have also characterized user behavior by analyzing the structural and dynamical patterns of the complex networks emergent from the mention and retweet networks. Our results suggest that the collective attention is driven by a very small fraction of users. Furthermore, we have analyzed the interactions taking place among politicians, observing a lack of debate. Finally, we develop a network growth model to reproduce the interactions taking place among politicians.

Clinical and epidemiological features of patients with COVID-19 reinfection: a systematic review.

Recurrent positivity in a patient with COVID-19 may be due to various reasons, not necessarily reinfection. There is concern about the occurrence frequency of reinfection. Five databases and a preprint/preprint repository were searched. All case reports, case series, and observational studies were included. Bias was assessed for each study with the Newcastle-Ottawa Scale tool and reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA-2020). After eligibility, 77 studies were included for qualitative synthesis (52 case reports, 21 case series, and four case-controls; 1131 patients included). Of these, 16 studies described a second contact with the SARS-CoV-2 positive case, five studies described healthcare profession-related infection, ten studies described that the source of reinfection was likely to be from the community, one study described travel-related infection, nine studies described vulnerability-related infection due to comorbidity. The mean number of days from discharge or negative test to reinfection ranged from 23.3 to 57.6 days across the different included studies. The risk of bias for all case report/series studies was moderate/high. For observational studies, the risk of bias was low. Reinfection of patients with COVID-19 occurs between the first and second month after the first infection, but beyond, and 90 days have been proposed as a point to begin to consider it. The main factor for reinfection is contact with COVID-19 positive cases.

Fungi and humans: closer than you think.

The budding yeast, Saccharomyces cerevisiae, has long been used as a model system to study the functions of human genes. Now that the genome sequences from several other fungal species are nearly complete, we can characterize the genetic diversity in the fungal kingdom at the genomic level. This diversity means that the number of human genes with homologues in the fungal kingdom is double that with homologues in S. cerevisiae only. Therefore, functional studies of human genes in the fungal model systems should look beyond S. cerevisiae.

Antioxidant: a new role for RU-486 and related compounds.

RU-486 (17 beta-hydroxy-4-dimethylaminophenyl-17-alpha-propenyl estrone 4,9 diene-3-one; mifepristone) is suggested to act by binding to progesterone and glucocorticoid receptors. Based on its chemical nature, we anticipated that RU-486 may have potent antioxidant properties. We used the oxidation of LDL as our model system. RU-486 and a similar compound, onapristone, at 1-5-microM concentrations, decreased the formation of oxidized LDL. LDL isolated from plasma of subjects who were orally supplemented with RU-486 was resistant to oxidation, as compared to LDL isolated from control plasma. The antioxidant effect of RU-486 appears to reside in the dimethylaminophenyl side chain moiety. Reduction of the A-ring of the steroid molecule had no effect on its antioxidant property. Analogs of RU-486 which lack the dimethylaminophenyl group, were without antioxidant activity. Levonorgestrel, which lacks the dimethylaminophenyl group failed to inhibit the oxidation of LDL even at 100-microM levels. In contrast, ethinylestradiol and estradiol which do not possess the dimethylamino group, were able to inhibit the oxidation of LDL by virtue of their phenolic steroid "A" ring. Thus RU-486, with its long half life, high plasma concentrations, association with lipoproteins, and ability to readily enter the cell may have additional intra- and extra-cellular antioxidant effects.

Epidemiology of American tegumentary leishmaniasis in domestic dogs in an endemic zone of western Venezuela.

Domestic dogs are not only reservoir hosts of the American zoonotic visceral leishmaniasis (ZVL) but of the American zoonotic tegumentary leishmaniasis (ATL) as well, for different reasons. However it is still controversial to state that dogs are incriminated as ATL reservoir hosts as there is evidence that humans and dogs are likely to be exposed in the same way to sandfly vector. In Venezuela this issue has not been completely addressed, for this reason we selected a location inside Trujillo city to study eco-epidemiological conditions as well as to survey a significant sample of dogs by Montenegro Skin Test (MST). Antigen was prepared according to standard procedure using Leishmania (V) braziliensis promastigotes (80 microg/ml); response was read 48 hours post-inoculation with an induration size > 5 mm being considered as positive. The study place is an endemic mountainous semi-urban area located at 850-950 masl with an average rainfall of 150 mm/year. We evaluated 61 dogs in 46 houses with 168 human beings. Among the human population 27 cases of ATL were reported (16.1%). With the MST we found 19 positive-reaction dogs (31%) (mean MST size of 9.58 mm, 95% CI: 8.41-10.75) in 13 houses (28%). Multivariate analysis did not reveal significant association between domestic MST positive-dog ownership and human ATL cases (RR = 1.48, p = 0.28). Although some studies have indicated that dog ownership and dog infection rates are associated with an increased risk of human disease in different evaluated places, this question has not been completely answered in Venezuelan studied zones, further research is necessary.

Congenital and Neonatal Chikungunya in Colombia.

In Latin America and the Caribbean (LAC), chikungunya (CHIK) viral infection has emerged as a significant arboviral disease. This rapidly expanding vector-borne viral illness is associated with a substantial burden of disease in terms of acute illness and also in terms of long-term sequelae. In addition, this viral pathogen has the ability to impact different populations including pregnant women and newborns. Despite the growing threat of this arboviral infection to the region, there are insufficient reports or studies attempting to delineate the clinical and epidemiological features of congenital and neonatal cases of CHIK in LAC. In this study, we present a case of congenital CHIK and a case of neonatal CHIK infection identified in Santander, Colombia. We discuss the potential neurological impact and sequelae of CHIK infection acquired during the neonatal period. There is an urgent need for further epidemiological and clinical studies to better understand the impact of CHIK in endemic areas in LAC.