COVID-19 patients with increasing age experience differential time to initial medical care and severity of symptoms.

We conducted a retrospective observational study in patients with laboratory-confirmed coronavirus disease (COVID-19) who received medical care in 688 COVID-19 ambulatory units and hospitals in Mexico City between 24 February 2020 and 24 December 2020, to study if the elderly seek medical care later than younger patients and their severity of symptoms at initial medical evaluation. Patients were categorised into eight groups (<20, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 and ≥80 years). Symptoms at initial evaluation were classified according to a previously validated classification into respiratory and non-respiratory symptoms. Comparisons between time from symptom onset to medical care for every age category were performed through variance analyses. Logistic regression models were applied to determine the risk of presenting symptoms of severity according to age, and mortality risk according to delays in medical care. In total, 286 020 patients were included (mean age: 42.8, s.d.: 16.8 years; 50.4% were women). Mean time from symptom onset to medical care was 4.04 (s.d.: 3.6) days and increased with older age categories (P < 0.0001). Mortality risk increased by 6.4% for each day of delay in medical care from symptom onset. The risk of presenting with the symptoms of severity was greater with increasing age categories. In conclusion, COVID-19 patients with increasing ages tend to seek medical care later, with higher rates of symptoms of severity at initial presentation in both ambulatory units and hospitals.

T-cell tolerance as a potential effect of congenital leishmaniasis on offspring immunity.

Congenital transmission of leishmaniasis is recognized in cases detected by passive surveillance. Most cases are from low-resource countries, limiting the study of several important aspects of this route of infection, including the offspring's immune response. Studies on natural and experimentally infected animals suggest that parasites might be transmitted to the embryo or foetus at any time during pregnancy. As immune system undergoes sequential stages of development, an infection before the time of self-recognition could lead to central tolerance, making an individual specifically tolerant and susceptible to infection. In the alternative scenario, infection after self-recognition would allow the proper development of T-lymphocyte clones in response to Leishmania antigens, providing resistance to the disease. Newborns undergo a transient period of low expression of several immune surface molecules and a naïve adaptive immune response with no memory, which together might contribute to slow elimination of the parasite over several months. This insight is a proposed independent mechanism of the previously proven T-cell exhaustion and must be investigated. Analyses of infected placenta, cord blood and infant immunity are required for a better understanding of immunity in congenital leishmaniasis infection.

Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals in vitro.

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps-SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps-SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.

A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice.

Ovine interferon tau (IFN-τ) is a unique type I interferon with low toxicity and a broad host range in vivo. We report the generation of a nonreplicative recombinant adenovirus expressing biologically active IFN-τ. Using the B6.A2G-Mx1 mouse model, we showed that single-dose intranasal administration of recombinant Ad5-IFN-τ can effectively prevent lethality and disease induced by highly virulent hv-PR8 influenza virus by activating the interferon response and preventing viral replication.

Metal enrichment of soils following the April 2012-2013 eruptive activity of the Popocatépetl volcano, Puebla, Mexico.

We analyzed the total (Zn, Pb, Ni, Hg, Cr, Cd, Cu, As) and partially leachable metals (PLMs) in 25 ash and soil samples from recent (2012-2013) eruptions of the Popocatépetl Volcano in Central Mexico. More recent ash and soil samples from volcanic activity in 2012-2013 had higher metal concentrations than older samples from eruptions in 1997 suggesting that the naturally highly volatile and mobile metals leach into nearby fresh water sources. The higher proportions of As (74.72%), Zn (44.64%), Cu (42.50%), and Hg (32.86%) reflect not only their considerable mobility but also the fact that they are dissolved and accumulated quickly following an eruption. Comparison of our concentration patterns with sediment quality guidelines indicates that the Cu, Cd, Cr, Hg, Ni, and Pb concentrations are higher than permissible limits; this situation must be monitored closely as these concentrations may reach lethal levels in the future.

Characterization of As and trace metals embedded in PM10 particles in Puebla City, México.

Forty-eight air-filter samples (PM10) were analysed to identify the concentration level of partially leached metals (PLMs; As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and V) from Puebla City, México. Samples were collected during 2008 from four monitoring sites: (1) Tecnológico (TEC), (2) Ninfas (NIN), (3) Hermanos Serdán (HS) and (4) Agua Santa (AS). The results indicate that in TEC, As (avg. 424 ng m(-3)), V (avg. 19.2 ng m(-3)), Fe (avg. 1,202 ng m(-3)), Cu (avg. 86.6 ng m(-3)), Cr (41.9 ng m(-3)) and Ni (18.6 ng m(-3)) are on the higher side than other populated regions around the world. The enrichment of PLMs is due to the industrial complexes generating huge dust particles involving various operations. The results are supported by the correlation of metals (Mn, Cd and Co) with Fe indicating its anthropogenic origin and likewise, As with Cd, Co, Fe, Mn, Pb and V. The separate cluster of As, Fe and Mn clearly signifies that it is due to continuous eruption of fumaroles from the active volcano Popocatépetl in the region.

Immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells.

Among cells of the immune system, CD11c(+) and DEC-205(+) splenic dendritic cells primarily express the cellular receptor (alpha-dystroglycan [alpha-DG]) for lymphocytic choriomeningitis virus (LCMV). By selection, strains and variants of LCMV that bind alpha-DG with high affinity are associated with virus replication in the white pulp, show preferential replication in a majority of CD11c(+) and DEC-205(+) cells, cause immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to alpha-DG are associated with viral replication in the red pulp, display minimal replication in CD11c(+) and DEC-205(+) cells, and generate a robust anti-LCMV cytotoxic T lymphocyte response that clears the virus infection. Differences in binding affinities can be mapped to a single amino acid change in the viral glycoprotein 1 ligand that binds to alpha-DG. These findings indicate that receptor-virus interaction on dendritic cells in vivo can be an essential step in the initiation of virus-induced immunosuppression and viral persistence.

Molecular analysis of the interaction of LCMV with its cellular receptor [alpha]-dystroglycan.

alpha-Dystroglycan (DG) has been identified as the cellular receptor for lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV). This subunit of DG is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ECM) and a beta-DG transmembrane component, which interacts with the actin-based cytoskeleton. In addition, DG exhibits a complex pattern of interaction with a wide variety of ECM and cellular proteins. In the present study, we characterized the binding of LCMV to alpha-DG and addressed the role of alpha-DG-associated host-derived proteins in virus infection. We found that the COOH-terminal region of alpha-DG's first globular domain and the NH2-terminal region of the mucin-related structures of alpha-DG together form the binding site for LCMV. The virus-alpha-DG binding unlike ECM alpha-DG interactions was not dependent on divalent cations. Despite such differences in binding, LCMV and laminin-1 use, in part, an overlapping binding site on alpha-DG, and the ability of an LCMV isolate to compete with laminin-1 for receptor binding is determined by its binding affinity to alpha-DG. This competition of the virus with ECM molecules for receptor binding likely explains the recently found correlation between the affinity of LCMV binding to alpha-DG, tissue tropism, and pathological potential. LCMV strains and variants with high binding affinity to alpha-DG but not low affinity binders are able to infect CD11c+ dendritic cells, which express alpha-DG at their surface. Infection followed by dysfunction of these antigen-presenting cells contributes to immunosuppression and persistent viral infection in vivo.

Altered lymphocyte homeostasis after oral prion infection in mouse.

Transmissible spongiform encephalopathies (TSEs) or prion diseases develop as central nervous system (CNS) disorders characterized by extremely long incubation periods. Although TSEs do not go along with inflammatory infiltrates and/or antibody production against the prion protein (PrP(Sc)), the immune system plays an important role in pathogenesis as long as different lymphoid organs (Peyer's patches, lymph nodes and spleen) may facilitate the accumulation and further spread of prions after peripheral exposure. In this work we investigated the changes in lymphoid and dendritic cell (DC) populations as well as the implications of different cytokines during disease progression after experimental oral inoculation of prions in a transgenic mouse model. At different days post-inoculation (dpi), T and B lymphocytes and DC populations from lymphoid organs, blood and brain were analyzed by flow cytometry and immunohistochemistry. Besides time related variations in lymphoid cell numbers due to the aging of the animals significant changes related with the infection were found in mesenteric lymph nodes, peripheral blood leukocytes (PBLs) as well as in spleen, affecting the CD4/CD8 ratio. In contrast, little or no variation was detected in Peyer's Patches or in thymus either associated with aging or the infection status. At individual time points significant differences between infected and control mice were seen in the CD8, CD4 and DC populations, with less evidence of differences in the B cell compartment. Finally, a pro-inflammatory phenotype occurred at early times in the spleen, where the levels of lymphotoxin-beta mRNA were found augmented with respect to controls. Altogether, these results suggest that normal regulation of lymphocyte populations becomes altered along the progression of a prion infection.

Arenavirus diversity and evolution: quasispecies in vivo.

Arenaviruses exist as viral quasispecies due to the high mutation rates of the low-fidelity viral RNA-dependent RNA polymerase (RdRp). This genomic heterogeneity is advantageous to the population, allowing for adaptation to rapidly changing environments that present varying types and degrees of selective pressure. The significant variation in biological properties observed among lymphocytic choriomeningitis virus (LCMV) strains, the prototypic arenavirus, indicates to what extent a quasis-pecies dynamics may play a role in arenavirus adaptability and pathogenesis. Several aspects of arenavirus variability and its contribution to pathogenesis will be discussed.

Bioaccumulation of trace metals in farmed pacific oysters Crassostrea gigas from SW Gulf of California coast, Mexico.

The aim of the study was to evaluate the bioavailability of trace metals (Chromium, Copper, Nickel, Lead, Zinc, Cadmium, Arsenic, and Mercury) in the commercially consumed Crassostrea gigas oysters collected over a 12-month growth period (2011-12) from an experimental cultivation farm in La Pitahaya, Sinaloa State, Mexico. Sediment and water samples were also collected from four different zones adjacent to the cultivation area to identify the concentration patterns of metals. The results revealed that sewage disposals, fertilizers used for agricultural practices and shrimp culture are the major sources for the enrichment of certain toxic metals. The metal concentrations in oysters presented a decreasing order of abundance (all values in mg Kg-1): Zn (278.91 ± 93.03) > Cu (63.13 ± 31.72) > Cr (22.29 ± 30.23) > Cd (14.54 ± 4.28) > Ni (9.41 ± 11.33) > Pb (2.22 ± 1.33) > As (0.58 ± 0.91) > Hg (0.04 ± 0.06). Bioconcentration Factor (BCF) and Biota Sediment Accumulation Factor (BSAF) exhibited that C. gigas in the region are strong accumulators for Zn and Cd respectively. Thus, the present study proves to fulfill the gap in understanding the rate of bioaccumulation of metals in C. gigas which is regarded as the most sought after oyster species globally.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.

Infection of dendritic cells by lymphocytic choriomeningitis virus.

Dendritic cells (DCs) comprise the major antigen-presenting cells (APCs) of the host, uniquely programmed to stimulate immunologically naïve T lymphocytes. Viruses that can target and disorder the function of these cells enjoy a selective advantage. The cellular receptor for lymphocytic choriomeningitis virus (LCMV), Lassa fever virus (LFV), and several other arenaviruses is alpha-dystroglycan (alpha-DG). Among cells of the immune system, CD11c+ and DEC-205+ DCs primarily and preferentially express alpha-DG. By selection, strains and variants of LCMV generated as quasi-species that bind alpha-DG with high affinity replicate in the majority of CD11c+ and DEC-205+ (>75%) DCs, causing a generalized immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to alpha-DG display minimal replication in CD11c+ and DEC-205+ DCs (<10%), rarely replicate in the white pulp, and generate a robust anti-LCMV CTL response that clears the virus infection. Hence, receptor-virus interaction on DCs in vivo is an essential step in the initiation of virus-induced immunosuppression and viral persistence. Investigation into the mechanism of how virus-infected DCs cause immunosuppression reveals loss of MHC class II surface expression and costimulatory molecules on surface of such DCs. As a consequence DCs are unable to act as APCs, initiate immune responses, and have a defect in migration into the T cell area. These data indicate that LCMV infection influences DC maturation and migration, leading to decreased T cell stimulatory capacity of DCs, events essential for the initiation of immune responses. Because several other viruses known to cause immunosuppression (HIV, measles) interact with DCs, the observations noted here are likely a common selective mechanism by which viruses also are able to evade the host's immune system.

Biochemical and structural studies with neutralizing antibodies raised against foot-and-mouth disease virus.

The function of a loop exposed on the aphthovirus capsid (the G-H loop of protein VP1) has been explored by combining genetic and structural studies with viral mutants. The loop displays a dual function of receptor recognition and interaction with neutralizing antibodies. Remarkably, some amino acid residues play a critical role in both such disparate functions. Therefore residues subjected to antibody pressure for variation may nevertheless maintain a role in receptor recognition for which invariance is a requirement. Evolution of FMDV in cell culture may relax the requirements at this site and allow further increase of antigenic diversification. Essential residues at one stage of virus evolution may become dispensable at another not very distant point in the evolutionary landscape. Implications for FMDV evolution and vaccine design are discussed.

Population dynamics in the evolution of RNA viruses.

RNA virus quasispecies are subjected to processes of positive Darwinian selection, to a very active and continuous negative selection and to random genetic drift. The course of RNA virus evolution is often unpredictable, and recent results suggest that even highly conserved motifs, once regarded as essential for infectivity, may be rendered dispensable by singular evolutionary events. An immediate consequence of the quasispecies genetic organization of RNA viruses is a surprising ability to gain fitness once a minimal replication ability is established in a biological environment. The unique features of RNA genetics should not be underestimated since they are at the basis of the emergence of new viral diseases and of the current difficulties to control many diseases associated variable viruses.

Evidence of activation and suppression during the early immune response to foot-and-mouth disease virus.

Foot-and-mouth disease virus causes a serious disease of livestock species, threatening free global trade and food security. The disease spreads rapidly between animals, and to ensure a window of opportunity for such spread, the virus has evolved multiple mechanisms to subvert the early immune response. The cycle of infection in the individual animal is very short, infection is initiated, disseminated throughout the body and infectious virus produced in <7 days. Foot-and-mouth disease virus has been shown to disrupt the innate response in vitro and also interacts directly with antigen-presenting cells and their precursors. This interaction results in suboptimal immune function, favouring viral replication and the delayed onset of specific adaptive T-cell responses. Detailed understanding of this cycle is crucial to effectively control disease in livestock populations. Knowledge-based vaccine design would specifically target and induce the immunological mechanisms of early protection and of robust memory induction. Specifically, information on the contribution of cytokines and interferon, innate immune cells as well as humoral and cellular immunity can be employed to design vaccines promoting such responses. Furthermore, understanding of viral escape mechanisms of immunity can be used to create attenuated viruses that could be used to develop novel vaccines and to study viral pathogenesis.

Metal concentrations in water and sediments from tourist beaches of Acapulco, Mexico.

A survey on the metal concentrations (As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, V, Zn) in beach water and sediments is reported from the tourist destination of Acapulco city on the Pacific coast of Mexico. The concentration of dissolved trace metals (DTMs) in beach water and acid leachable trace metals (ALTMs) in sediments indicated that they are anthropogenic in nature due to the increased tourist activities in the crowded beach locations. The statistical analysis indicates Fe and Mn play a major role as metal scavengers in both the medium (water and sediment) and the higher value of other metals is site specific in the study area, indicating that they are transported from the local area. Comparison results suggest that the beach water quality has deteriorated more than the sediments and special care needs to be taken to restore the beach quality.