Sexual dimorphism in the dwarf round ray Urotrygon nana.

This paper presents information on the morphological, morphometric, and dental sex differences in the dwarf round ray Urotrygon nana. We recorded 12 morphological traits, sex, the distribution pattern of dermal denticles, the number of tooth rows, and the tooth shape of 466 individuals. The disc width of females ranged from 50 to 172 mm and that of males ranged from 53 to 135 mm. A neuronal classification model and a correspondence analysis showed that female disc width was 21.5% broader, and the distance from the rostrum to the anus was 17.7% longer than that of males, whereas males presented 19.5% greater distance between the nostrils, 9.7% greater preorbital snout length, 6.8% greater cloaca to caudal-fin length, 2.7% greater interorbital distance, and 1.1% greater total length than females. The disc of adult males, including the abdominal cavity area, was densely covered with dermal denticles, which were slightly larger than those observed in females. Females presented homodont dentition with molariform teeth and a smooth lozenge-shaped crown with rounded margins. Males exhibited homodonty but with tooth morphology variations in individuals of different sizes (from molariforms to sharper cusp teeth). There were changes in disc shape (from subcircular to oval), distribution and size of dermal denticles (more abundant and larger), and tooth shape (from molariform to monocuspid teeth) during male development, from neonates to adults. U. nana exhibited sexual dimorphism in size, disc shape, number and shape of teeth, and distribution and size of dermal denticles.

Cadmium (Cd) distribution and soil-plant relationship in cacao farms in Costa Rica.

The current cadmium (Cd) regulations in chocolate threaten the cacao supply chain in several Latin American countries. The factors contributing to Cd accumulation in cacao beans have been poorly studied in Central America. The objective of this research was to identify the location of Cd hotspots as well as soil properties and management practices influencing the Cd concentration in cacao beans. A survey was carried out and soil, leaf, and beans were sampled from 150 farms in the three principal cacao-producing regions in Costa Rica. Total soil Cd concentration ranged from <0.1 to 1.05 (average 0.22 mg kg-1) which is typical of uncontaminated soils. Bean Cd concentration ranged from 0.12 to 3.23 (average 0.56 mg kg-1) and 22% of the samples exceeded the selected threshold of 0.80 mg kg-1, located mostly in the Huetar Caribe and Huetar Norte regions. Variability in bean Cd concentration was better explained by total soil Cd and soil organic carbon (SOC) (R2 = 0.62, p < 0.05). In addition, bean Cd concentration was affected by leaf nutrient content and management practices. Leaf Zn and P were positively correlated with bean Cd while K and Mn were negatively correlated (p < 0.05). Farm altitude and orchard age were also negatively correlated with bean Cd. Overall, this study shows that bean Cd contamination does not reach the extent observed in other Latin American countries such as Ecuador, Colombia, or Honduras. Nevertheless, research is needed in hotspot areas to assess the feasibility of potential mitigation strategies, particularly the use of mineral or organic soil amendments, which may allow better for planning in existing plantations or the expansion into new cacao-growing areas in the country.

Quasi-Diamond Platelet-Shaped Zinc Oxide Nanostructures Display Enhanced Antibacterial Activity.

The current study compares the antibacterial activity of zinc oxide nanostructures (neZnO). For this purpose, two bacterial strains, Escherichia coli (ATCC 4157) and Staphylococcus aureus (ATCC 29213) were challenged in room light conditions with the aforementioned materials. Colloidal and hydrothermal methods were used to obtain the quasi-round and quasi-diamond platelet-shape nanostructures. Thus, the oxygen vacancy (VO ) effects on the surface of neZnO are also considered to assess its effects on antibacterial activity. The neZnO characterization was achieved by X-ray diffraction (XRD), a selected area electron diffraction (SAED) and Raman spectroscopy. The microstructural effects were monitored by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, optical absorption ultraviolet visible spectrophotometry (UV-Vis) and X-ray photoelectron spectroscopy (XPS) analyses complement the physical characterization of these nanostructures; neZnO caused 50 % inhibition (IC50 ) at concentrations from 0.064 to 0.072 mg/mL for S. aureus and from 0.083 to 0.104 mg/mL for E. coli, indicating an increase in activity against S. aureus compared to E. coli. Consequently, quasi-diamond platelet-shaped nanostructures (average particle size of 377.6±10 nm) showed enhanced antibacterial activity compared to quasi-round agglomerated particles (average size of 442.8±12 nm), regardless of Vo presence or absence.

Monitoring cadmium concentrations in cacao: inter-laboratory variation and the effect of sample size on variability among ready-for-sale beans.

Since the implementation of new EU limits on cadmium (Cd) in cacao-derived products, reliable measurements of the Cd concentration in cacao samples have become even more important. This study was set up to analyse the robustness of the measured Cd concentrations in cacao as affected by sampling strategy and by the laboratory receiving these samples. Six different homogenised cacao liquor samples were sent to 25 laboratories, mainly located in Latin America. On average, only 76% of the laboratories reported acceptable results per sample using internationally accepted criteria. More unreliable data was obtained when Atomic Absorption Spectroscopy (AAS) rather than Inductively Coupled Plasma (ICP) instruments were used or where concentrations were outside the calibration range. Subsequently, four commercial lots in Ecuadorian warehouses were sampled to identify the variation among beans, bags and replicate chemical analyses of ground samples. Simulations indicate that a composite sample should be made from at least 10 bags on a pallet and at least 60 beans should be ground prior to analysis to obtain an acceptable CV below 15%. This study shows that current Cd analyses in cacao on the market are neither sufficiently accurate nor precise and that more control on laboratory certifications is needed for reliable screening of Cd in cacao.

Heavy metal(loid)s contamination in water and sediments in a mining area in Ecuador: a comprehensive assessment for drinking water quality and human health risk.

Elevated heavy metal(loid)s concentrations in water lower its quality posing a threat to consumers. This study aims to assess the human health risk caused by heavy metal(loid)s in tap water in Santa Rosa city, Ecuador, and the ecological risk of stream water and sediments in the Santa Rosa River. Concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were evaluated in tap waters, stream waters, and sediment samples during the rainy and dry seasons. The Metal Index (MI), Geo-accumulation Index (Igeo), Potential Ecological Risk Index (PERI), and the levels of carcinogenic (CR) and non-carcinogenic risk (HQ) were determined. The results revealed severe pollution levels, mainly in Los Gringos and El Panteon streams, both tributaries of the Santa Rosa River, the primary water source for Santa Rosa inhabitants. More than 20% of the surface water samples showed severe contamination (MI > 6), and 90% of the tap water samples presented a MI value between 1 and 4, which indicates slight to moderate pollution. Drinking water displayed high levels of As, with 83% of the tap water samples collected from households in the dry season above the recommended concentration set by the World Health Organization and Ecuadorian legislation. The Igeo-Cd in the sediment samples was significantly high (Igeo > 3), and the PERI showed very high ecological risk (PERI > 600), with Cd as the main pollutant. HQ and CR were above the safe exposure threshold, suggesting that residents are at risk from tap water consumption, with As being the primary concern.

Revealing the pathways of cadmium uptake and translocation in cacao trees (Theobroma cacao L.): A 108Cd pulse-chase experiment.

The pathways through which cadmium (Cd) is taken up and loaded into cacao beans (nibs) are yet to be revealed. Previous work suggested that Cd loading into cacao nibs may occur via direct xylem uptake rather than phloem-mediated redistribution from the leaves. A stable isotope (108Cd) pulse-chase experiment was set up to identify the pathways of Cd loading into cacao nibs. The topsoil beneath two mature cacao trees in the field was enriched in 108Cd via surface irrigation with a spiked solution. The increase in 108Cd isotopic abundance (IA) in the plant tissues was followed up for 548 days after spiking. The 108Cd IA in the plant tissues increased from natural abundance (0.89 %) to 7.0 % (tree A) and 10.1 % (tree B) at equilibrium. The tracer was taken up in the plant tissues in the order immature leaves > mature leaves > nibs in both trees, while tracer uptake in flowers and cherelles was less consistent between the trees. Half of the equilibrium 108Cd IA was reached in the nibs at 191 days after spiking, significantly later than corresponding values for mature (151 days) and immature leaves (117 days). Pod maturation from flower stage takes about 6 months with most Cd entering the nibs at the last stage of development. The rather slow rise in the 108Cd IA in the nibs compared to the leaves hence suggests that Cd in cacao nibs likely originates from phloem-redistribution from the stem, branches or mature leaves and not from direct root-to-nib transport via the xylem.

Reducing cadmium bioaccumulation in Theobroma cacao using biochar: basis for scaling-up to field.

The intake of Cd-enriched food is the main Cd pathway for the nonsmoking population. In some cases, Cd bioaccumulates in edible plant parts which comprise risk to consumers, because of Cd is a harmful heavy metal that can cause potent environmental and health hazards. For instance, Cd enrichment of cacao seeds have led to Cd enrichment of cacao-based products. In Latin America and the Caribbean, Cd bioaccumulation in cacao seeds occurs in different regions with diverse edaphoclimatic conditions, which makes it difficult to select soil remediation alternatives. Limited resources require that potential amendments must be carefully investigated through laboratory and/or greenhouse conditions before scaling up to field experiments. In this study, we evaluated the effectiveness of four biochars: coffee-, quinoa-, and inoculated- and palm-biochar, derived from three feedstocks: coffee husk, quinoa straw, and oil palm residues, respectively. Biochars were applied in two rates (1 and 2% w/w) in two soils, one moderately acidic and one slightly alkaline (Cd-spiked and non-spiked). CCN-51 cacao plants were used for the greenhouse experiment. After 130 days, biometric parameters, the bioavailability of Cd in the soil, and the concentration of Cd and mineral nutrients in the plants were measured. Quinoa biochar at the 2% significantly decreased (P < 0.01), by ∼71%, bioavailable Cd in moderately acidic and slightly alkaline soils, and leaf-Cd by ∼48%. Soil pH, electrical conductivity, and effective cation exchange capacity were significantly (P < 0.01) correlated with bioavailable soil and leaf-Cd. Biochar characteristics, such as ash contents, basic cations content, and surface functional groups could be used as indicators for the selection of biochars to reduce Cd uptake by cacao. Additionally, application of quinoa derived biochar provided P and K, which could increase productivity to offset mitigation costs. Overall, incorporation of quinoa biochar at 2% rate is effective for lowering bioavailable Cd in different soil types which reduces leaf-Cd in cacao plants.

HB-EGF Plays a Pivotal Role in Mucosal Hyperplasia During Otitis Media Induced by a Viral Analog.

Otitis media (OM), the most common childhood illness, can be caused by bacterial and/or viral infection. Hyperplasia of the middle ear (ME) mucosa is an important component of OM that contributes to its deleterious sequelae. Our previous research revealed that ME mucosal hyperplasia in bacterially induced OM was associated with expression of the heparin-binding epidermal growth factor (HB-EGF) gene, and that HB-EGF induced the proliferation of ME mucosal explants in culture. We used single-cell RNA-Seq to identify ME cells that express Hbegf and related genes involved in mediating responses to this factor. To determine the degree to which a viral infection might induce mucosal hyperplasia, and to assess the role of HB-EGF in hyperplasia in vivo, we used, Poly(I:C) to simulate a ME viral infection, Western blotting to confirm ME protein expression, and a specific inhibitor to block the effects of HB-EGF during OM. Genes for HB-EGF and its receptor were expressed in the ME primarily by epithelial, stromal and endothelial cells. Poly(I:C) induced prominent ME mucosal hyperplasia, peaking two days after ME injection. Immunostaining revealed that cleavage of proHB-EGF into its soluble form (sHB-EGF) was strongly induced in response to Poly(I:C). Inhibition of the sHB-EGF receptor dramatically reduced the hyperplastic response of the mucosa. The results demonstrate that a synthetic analog of viral double-stranded RNA interaction can induce OM including a strong proliferative response of the ME mucosa, independent of bacteria. They also indicate that HB-EGF is the dominant growth factor responsible for ME mucosal hyperplasia in vivo.

A transcytotic transport mechanism across the tympanic membrane.

Drug treatments for middle ear diseases are currently delivered systemically, or locally after opening the impermeable tympanic membrane (TM). We previously used bacteriophage display to discover novel peptides that are actively transported across the intact TM, with a variety of transport rates. Peptide structures were analyzed for evidence regarding the mechanism for this unexpected transport, which was then tested by the application of chemical inhibitors. Primary sequences indicated that trans-TM peptides share one of two amino acid motifs. Secondary structures revealed that linear configurations associate with higher transport rates than coiled structures. Tertiary analysis indicated that the shared sequence motifs are prominently displayed at the free ends of rapidly transported peptide phage. The shared motifs were evaluated for similarity to known motifs. The highest probability matches were for protein motifs involved in transmembrane transport and exosomes. Overall, structural findings suggest that the shared motifs represent binding sequences. They also implicate transcytosis, a polarized cell transport mechanism consisting of endocytosis, transcellular transport, and exocytosis. Inhibitor studies indicated that macropinocytosis, retrograde transport through Golgi and exocytosis participate in transport across the TM, consistent with transcytosis. This process can be harnessed to noninvasively deliver therapeutics to the middle ear.

A Screen of Autophagy Compounds Implicates the Proteasome in Mammalian Aminoglycoside-Induced Hair Cell Damage.

Introduction: Autophagy is a degradative pathway to safely break down and recycle dysfunctional cellular components. There is prior evidence of autophagy participation during hair cell (HC) damage. Our goal was to screen compounds targeting different aspects of autophagy for their effects on HC loss due to an ototoxic aminoglycoside, gentamicin (GM). Methods: The SELLECKChem autophagy compound library, consisting of 154 compounds with defined autophagy inducing or inhibitory activity, was used for targeted screening in vitro model of ototoxicity. Organ of Corti from postnatal days 3-5 pou4f3/GFP transgenic mice (HCs express green fluorescent protein) were utilized. The organs were micro-dissected, and basal and middle turns divided into micro-explants individually placed into the single wells of a 96-well plate. Samples were treated with 200 µM of GM plus three dosages of tested compound and cultured for 72 h. Negative controls were treated with media only; positive ototoxicity controls were treated with GM only. Results: The majority of the library compounds had no effect on GM-induced HC loss. However, 18 compounds exhibited a significant, protective effect, two compounds were protective at low dosage but showed enhanced GM toxicity at higher doses and one compound was toxic to HCs in the absence of GM. Conclusions: This study evaluated many autophagy compounds that have not been tested previously on HCs. The disparate results obtained underscore the complexity of autophagy events that can influence HC responses to aminoglycosides, but also implicate the proteosome as an important damage mechanism. The screening results can serve as basis for further studies with protective compounds as potential drug targets.

Probabilistic multi-pathway human health risk assessment due to heavy metal(loid)s in a traditional gold mining area in Ecuador.

Mining operations are important causes of environmental pollution in developing countries where mining waste management is not adequate. Consequently, heavy metal(loid)s are easily released into the environment, being a potential risk to human health. This study carries out a Bayesian probabilistic human health risk assessment, related to multi-pathway exposure to heavy metal(loid)s in a gold mining area in Southern Ecuador. Concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn in tap water, surface water, and soil samples, were analyzed to assess the potential adverse human health effects based on the Hazard Index (HI) and Total cancer risk (TCR). Adults and children residents were surveyed to adjust their exposure parameters to the site-specific conditions. Exposure to heavy metal(loid)s resulted in unacceptable risk levels for human health in the two age groups, both carcinogenic (TCR > 1 × 10-5) and non-carcinogenic (HI > 1) through ingestion of tap water and incidental ingestion of surface water. Sensitivity analysis showed that As concentration in waters and exposure frequency were the main contributors to risk outcome. Exposure to soil via accidental ingestion and dermal contact was below the safety limit, not posing a risk to human health. These findings can provide a baseline for the environmental management of the mining area and indicate the need for further research on As pollution in water and its implications on the health of the inhabitants of mining communities.

Ecological and probabilistic human health risk assessment of heavy metal(loid)s in river sediments affected by mining activities in Ecuador.

Gold mining is a significant source of metal(loid)s released into the environment. It is an issue of concern due to the potential adverse health effects associated with exposure to toxic elements. This study aimed to assess the ecological and human health risk caused by heavy metal(loid)s exposure in river sediments in Ponce Enríquez, one of the most important mining sites in Ecuador. Concentrations of As, Cd, Cu, Pb, and Zn were evaluated in 172 sediment samples to determine the Potential ecological risk (RI) and the carcinogenic (CR) and non-carcinogenic risk (HQ). The human exposure to polluted sediments during recreational activities was computed using Bayesian probabilistic models. Residents were randomly surveyed to adjust the risk models to the specific population data. More than 68% of the sampling stations pose a severe As and Cd ecological risk index ([Formula: see text] > 320). Likewise, residents exposed to river sediments showed a non-acceptable carcinogenic risk by incidental ingestion, being As the primary contributor to overall cancer in both children and adults receptors. Moreover, non-carcinogenic risk through the incidental ingestion of sediments was above the safe limit for children. This is the first study conducted in a mining region in Ecuador that reveals the severe levels of ecological and human health risk to which the population is exposed. These results can be applied as a baseline to develop public health strategies to monitor and reduce the health hazards of the residents of mining communities.

Spatial pattern of distribution and reproductive strategy of vermiculate electric-rays Narcine vermiculatus.

In the study, the authors evaluate the spatial distribution pattern of vermiculate electric-ray Narcine vermiculatus using geostatistical techniques to predict its spatial distribution and indicate its reproduction strategy. From January 2008 to December 2009, 3333 specimens of vermiculate electric-ray were caught. Total length (LT ), sex, maturity stage, catch location and depth were recorded for each specimen. The LT of vermiculate electric-ray ranged from 6.7-24.6 cm. The authors estimate an irregular spatial structure, with a high-density patch ( x ¯ = 53 ind. ha-1 ) located on the east coast, which concentrates 65.2% of the specimens. The high-density patch consists mainly of large juveniles (13.3-19.5 cm LT ), sub-adults (14.0-19.8 cm LT ) and young adults (14.7-21.3 cm LT ). Data indicate that adults migrate to the high-density patch to reproduce. Males reached maturity at 14.5 cm LT , whereas females reached maturity at 19.3 cm LT . Vitellogenesis in female vermiculate electric-ray begins in June; ovulation, mating, fertilization and gestation in October and birth begins in February. This indicates an annual cycle with vitellogenesis and consecutive gestation, in females synchronized in reproduction. Fecundity was 1-8 ( x ¯ = 4), and the sex ratio of embryos was 1:1. The birth occurred between February and April, with an average size at parturition of 6.3 cm LT . Incidental capture of sub-adults and adults of N. vermiculatus by bottom trawls threatens the survival of this species.

Surface soil liming reduces cadmium uptake in cacao seedlings but subsurface uptake is enhanced.

Cadmium concentrations in cacao (Theobroma cacao L.) beans from South America often exceed trade limits. Liming soil is advocated as a remediation option, but amendments cannot be incorporated into the entire root zone without harming the trees. An experiment was set up to identify how Cd uptake varies within the root zone when surface and subsurface soil layers are either limed or not. The experiment used 22-cm-height pots with top and bottom layers using surface and subsurface soil samples from a cacao field. The potted soils were either surface limed or not or fully limed and layers spiked with stable 108 Cd isotope in various combinations to trace the plant Cd provenance. The root distribution was neither affected by liming nor by soil source; 70% of the root biomass was present in the top layer. Plants grown on the fully limed surface soil had 1.7 times lower Cd concentrations in leaves than the unlimed treatments, whereas this concentration was 1.2 times lower when only the top layer was limed (surface soil used in both layers). The isotope dilution data showed that surface soil liming enhanced Cd uptake from the unlimed bottom layer compared with the unlimed soil, suggesting compensating mechanisms. The pots containing surface soil over subsurface soil also showed that compensating effect but, due to lower phytoavailable Cd in the subsurface soil, surface liming still effectively reduced foliar Cd. We conclude that liming might be a feasible mitigation strategy, but its effectiveness is limited when Cd phytoavailability remains untreated in the subsurface layer.

Selection of a Single Domain Antibody, Specific for an HLA-Bound Epitope of the Mycobacterial Ag85B Antigen.

T cells recognizing epitopes on the surface of mycobacteria-infected macrophages can impart protection, but with associated risk for reactivation to lung pathology. We aimed to identify antibodies specific to such epitopes, which carry potentials for development toward novel therapeutic constructs. Since epitopes presented in the context of major histocompatibility complex alleles are rarely recognized by naturally produced antibodies, we used a phage display library for the identification of monoclonal human single domain antibody producing clones. The selected 2C clone displayed T cell receptor-like recognition of an HLA-A*0201 bound 199KLVANNTRL207 peptide from the Ag85B antigen, which is known to be an immunodominant epitope for human T cells. The specificity of the selected domain antibody was demonstrated by solid phase immunoassay and by immunofluorescent surface staining of peptide loaded cells of the T2 cell line. The antibody affinity binding was determined by biolayer interferometry. Our results validated the used technologies as suitable for the generation of antibodies against epitopes on the surface of Mycobacterium tuberculosis infected cells. The potential approaches forward the development of antibody in immunotherapy of tuberculosis have been outlined in the discussion.

Presence of pregnant females of the Gorgona guitarfish, Pseudobatos prahli, in the Mexican tropical Pacific.

Five specimens (four females and one male) of the Gorgona guitarfish, Pseudobatos prahli, were sighted during two dives carried out off the western Gulf of Tehuantepec. This document describes the reproductive condition of three adult females captured, two of which had uterine eggs, whereas one had embryos. The sighting and capture of specimens occurred during two Tehuano wind events; the authors, therefore, believe that variations in temperature and dissolved oxygen could have affected P. prahli, leading it to carry out temporal migrations towards coastal shallow waters.

A kinase inhibitor screen identifies signaling pathways regulating mucosal growth during otitis media.

Otitis media, the most common disease of childhood, is characterized by extensive changes in the morphology of the middle ear cavity. This includes hyperplasia of the mucosa that lines the tympanic cavity, from a simple monolayer of squamous epithelium into a greatly thickened, respiratory-type mucosa. The processes that control this response, which is critical to otitis media pathogenesis and recovery, are incompletely understood. Given the central role of protein phosphorylation in most intracellular processes, including cell proliferation and differentiation, we screened a library of kinase inhibitors targeting members of all the major families in the kinome for their ability to influence the growth of middle ear mucosal explants in vitro. Of the 160 inhibitors, 30 were found to inhibit mucosal growth, while two inhibitors enhanced tissue proliferation. The results suggest that the regulation of infection-mediated tissue growth in the ME mucosa involves multiple cellular processes that span the kinome. While some of the pathways and processes identified have been previously implicated in mucosa hyperplasia others are novel. The results were used to generate a global model of growth regulation by kinase pathways. The potential for therapeutic applications of the results are discussed.

COVID-19. El manejo ambulatorio durante la transmisión comunitaria intensa / COVID-19. Ambulatory management during intense community transmission

RESUMEN La COVID-19, en los escasos seis meses de su presencia, ha provocado una crisis sanitaria mundial, con mayor impacto en los países más pobres. En la actualidad, existe un mejor conocimiento de la clínica de esta enfermedad y su relación con los fenómenos fisiopatológicos; sin embargo, dada la alta letalidad, el mayor enfoque de su manejo se ha orientado hacia el paciente hospitalizado o crítico. Esta información y experiencia se comparte con el fin de lograr reforzar una mejor atención a las personas afectadas por la COVID-19 desde sus primeros síntomas en el hogar, especialmente en estos momentos de amplia transmisión en la comunidad, donde los servicios de salud están seriamente limitados en recursos humanos y materiales. El objetivo es: i) evitar complicaciones más allá de las causadas por la propia evolución de la enfermedad; ii) determinar el momento adecuado para la referencia del paciente al hospital y reducir la letalidad; iii) reforzar el aislamiento de los casos; y iv) posiblemente, disminuir la progresión a una enfermedad severa. Incluye el manejo luego del alta hospitalaria, así como recomendaciones para considerar si los servicios de salud colapsan; indicaciones sobre cuándo dar de alta al paciente para que regrese al trabajo, y destaca la importancia del telemonitoreo para el éxito de este manejo en el contexto epidemiológico actual.

ABSTRACT The COVID-19, in the scant six months of its presence, has caused a global health crisis, with greater impact in the poorest countries. Currently, there is a better understanding of the clinic of this disease and its relationship with physiopathological phenomena; however, given the high lethality, the major focus of its management has been oriented towards the hospitalized or critical patient. This information and experience is shared in order to achieve and strengthen better care for people affected by COVID-19 from their first symptoms at home, especially at these times of extensive community transmission, where health services are seriously limited in human and material resources. The aim is to (i) avoid complications beyond those caused by the evolution of the disease itself; (ii) determine the appropriate time for patient referral to the hospital and reduce lethality; (iii) reinforce the isolation of cases; and (iv) possibly, decrease the progression to severe disease. It includes outpatient management after hospital discharge, as well as recommendations to consider if health services collapse; indications for when to discharge the patient for return to work, and highlights the importance of telemonitoring for the success of this practice in the current epidemiological context.

COVID-19: En este momento podría ser útil el tratamiento antiviral en casos leves / COVID-19: Antiviral treatment in mild cases could be useful at this time

RESUMEN La letalidad por COVID-19 así como su rápida diseminación son responsables de la actual crisis mundial; por ello, desde un inicio se buscaron medicamentos con acción antiviral frente a este agente. Es imposible, por ahora, saber qué persona en estado leve desarrollará una elevada carga viral o tiene una predisposición a desarrollar una respuesta extremada del sistema inmune, pero un tratamiento temprano en los casos leves no sólo garantizaría una mayor eficacia, sino que se evitarían los casos severos. En la actualidad no se dispone de ensayos clínicos, doble ciego, aleatroizados, ni metaanálisis para tomar decisiones seguras; mientras tanto, la pandemia avanza en nuestro país, generando dolor y muerte. En este contexto, en el Perú, las sociedades científicas han manifestado la necesidad del uso de medicamentos antivirales, aún con poca evidencia, basado en la probabilidad de éxito previo a un tratamiento, por sus efectos in vitro y por sus efectos clínicos tempranos, tales como: cloroquina, hidroxicloroquina, azitromicina, lopinavir, ritonavir. De esta manera, en el país desde el 29 de marzo de 2020, se dispone de una norma técnica del Ministerio de Salud, que facilita el uso de estos a nivel nacional para los casos moderados y severos. Consideramos que bajo un sistema estructurado, los centros de primer nivel de atención podrían tratar los casos leves de COVID-19. Nuestro país, a través de las estrategias de prevención y control de TB y de ITS/VIH/SIDA, tiene experiencia en el manejo de programas de tratamiento en dicho nivel. Los costos serán menores que los requeridos en el fortalecimiento del tercer nivel de atención.

ABSTRACT COVID-19's lethality as well as its rapid spread are responsible for the current world crisis; therefore, from the beginning, drugs with antiviral action against this agent were sought. It is impossible, for now, to know which person in a mild state will develop a high viral load or have a predisposition to develop an extreme response from the immune system, but early treatment in mild cases would not only guarantee greater efficacy, but would avoid severe cases. Currently, there are no double blind, randomized clinical trials or meta-analyzes available to make safe decisions; meanwhile, the pandemic is advancing in our country, generating pain and death. In this context, in Peru, scientific societies have expressed the need for the use of antiviral drugs, even with little evidence, based on the probability of success prior to treatment, for their in vitro effects and for their early clinical effects, such as: chloroquine, hydroxychloroquine, azithromycin, lopinavir, ritonavir. Thus, in the country since march 29, 2020, there is a technical standard from the Ministry of Health, which facilitates the use of these at the national level for moderate and severe cases. We believe that under a structured system, first-level care centers could treat mild cases of COVID-19. Our country, through strategies for the prevention and control of TB and ITS/HIV/AIDS, has experience in managing treatment programs at this level. The costs will be less than those required to strengthen the third level of care.