Biogenic Synthesis of Copper Nanoparticles: A Systematic Review of Their Features and Main Applications.

Nanotechnology is an innovative field of study that has made significant progress due to its potential versatility and wide range of applications, precisely because of the development of metal nanoparticles such as copper. Nanoparticles are bodies composed of a nanometric cluster of atoms (1-100 nm). Biogenic alternatives have replaced their chemical synthesis due to their environmental friendliness, dependability, sustainability, and low energy demand. This ecofriendly option has medical, pharmaceutical, food, and agricultural applications. When compared to their chemical counterparts, using biological agents, such as micro-organisms and plant extracts, as reducing and stabilizing agents has shown viability and acceptance. Therefore, it is a feasible alternative for rapid synthesis and scaling-up processes. Several research articles on the biogenic synthesis of copper nanoparticles have been published over the past decade. Still, none provided an organized, comprehensive overview of their properties and potential applications. Thus, this systematic review aims to assess research articles published over the past decade regarding the antioxidant, antitumor, antimicrobial, dye removal, and catalytic activities of biogenically synthesized copper nanoparticles using the scientific methodology of big data analytics. Plant extract and micro-organisms (bacteria and fungi) are addressed as biological agents. We intend to assist the scientific community in comprehending and locating helpful information for future research or application development.

In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer's Disease.

BACKGROUND: Despite research on the molecular bases of Alzheimer's disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers. METHODS: We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials. RESULTS: Our results demonstrated the increased bioactivity of three plants' metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau. CONCLUSIONS: This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

Technological trends and market perspectives for production of microbial oils rich in omega-3.

In recent years, foods that contain omega-3 lipids have emerged as important promoters of human health. These lipids are essential for the functional development of the brain and retina, and reduction of the risk of cardiovascular and Alzheimer's diseases. The global market for omega-3 production, particularly docosahexaenoic acid (DHA), saw a large expansion in the last decade due to the increasing use of this lipid as an important component of infant food formulae and supplements. The production of omega-3 lipids from fish and vegetable oil sources has some drawbacks, such as complex purification procedures, unwanted contamination by marine pollutants, reduction or even extinction of several species of fish, and aspects related to sustainability. A promising alternative system for the production of omega-3 lipids is from microbial metabolism of yeast, fungi, or microalgae. The aim of this review is to discuss the various omega-3 sources in the context of the global demand and market potential for these bioactive compounds. To summarize, it is clear that fish and vegetable oil sources will not be sufficient to meet the future needs of the world population. The biotechnological production of single-cell oil comes as a sustainable alternative capable of supplementing the global demand for omega-3, causing less environmental impact.

Green Synthesis of Silver Nanoparticles Mediated by Punica granatum Peel Waste: An Effective Additive for Natural Rubber Latex Nanofibers Enhancement.

Pomegranate waste poses an environmental challenge in Arequipa. Simultaneously, interest in sustainable materials like natural rubber latex (NRL) is growing, with Peruvian communities offering a promising source. This study explores the green synthesis of silver nanoparticles (AgNPs) using pomegranate peel extract and their incorporation into NRL nanofibers for enhanced functionalities. An eco-friendly process utilized silver nitrate and pomegranate peel extract as a reducing and capping agent to synthesize AgNPs. The resulting AgNPs and NRL/AgNPs nanofibers were characterized using imaging and spectroscopic techniques such as UV-vis, TGA, FTIR, XRD, Raman, SEM, and DLS. Green-synthesized AgNPs were spherical and crystalline, with an average diameter of 59 nm. They showed activity against K. pneumoniae, E. coli, B. cereus, and S. aureus (IC50: 51.32, 4.87, 27.72, and 69.72 µg/mL, respectively). NRL and NRL/AgNPs nanofibers (300-373 nm diameter) were successfully fabricated. The composite nanofibers exhibited antibacterial activity against K. pneumoniae and B. cereus. This study presents a sustainable approach by utilizing pomegranate waste for AgNP synthesis and NRL sourced from Peruvian communities. Integrating AgNPs into NRL nanofibers produced composites with antimicrobial properties. This work has potential applications in smart textiles, biomedical textiles, and filtration materials where sustainability and antimicrobial functionality are crucial.

Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products: potential pH-dependent inhibition explored through computer-aided drug design.

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite's N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite's changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

A new species of Andean frog of the genus Phrynopus (Anura: Strabomantidae) from southeastern Peru.

The Cordillera de los Andes is one of the most important regions for biodiversity. Among amphibians, many endemic species of terrestrial-breeding frogs have recently been discovered. Herein we describe Phrynopus sancristobali from the Andes of southeastern Peru based on molecular and morphological data. The new species is known from the ecotone between humid puna and montane forest at 3910 m a.s.l. on the left side of the Apurímac Valley in the Department of Ayacucho. The new species differs from congeners by having dorsum bearing pustules and light brown with dark brown reticulations surrounding the areolas, and coloration consisting of flanks golden brown with gray or dark brown marks, palms pale orange, soles deep orange, toes IV and V dark brown in dorsal and ventral view, belly cream to yellow with gray to light brown marks, and groin and throat deep orange. The snout-vent length (SVL) is 20.7 and 22.2 in two females, and 19.5 mm in one male. According to our phylogeny inferred using Maximum Likelihood with a concatenated dataset of three mitochondrial and two nuclear genes, P. sancristobali is sister taxon of P. apumantarum, recently described from Department Huancavelica. Our description extends the known geographic range of Phrynopus 73 km to the south, and P. sancristobali is the only species in the genus known to occur south of the Mantaro River, whose deep valley is hypothesized to be a biogeographic barrier for high-Andean organisms. The discovery of P. sancristobali confirms the high levels of endemism and beta diversity of Phrynopus in the moist puna grasslands and montane forests of the high Andes of Peru, and suggests that further work will reveal the presence of additional species in southern Peru.

A Systematic Review and Meta-Analysis Comparing the Diagnostic Accuracy Tests of COVID-19.

In this paper, we present a systematic review and meta-analysis that aims to evaluate the reliability of coronavirus disease diagnostic tests in 2019 (COVID-19). This article seeks to describe the scientific discoveries made because of diagnostic tests conducted in recent years during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Between 2020 and 2021, searches for published papers on the COVID-19 diagnostic were made in the PubMed database. Ninety-nine scientific articles that satisfied the requirements were analyzed and included in the meta-analysis, and the specificity and sensitivity of the diagnostic accuracy were assessed. When compared to serological tests such as the enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLIA), lateral flow immunoassay (LFIA), and chemiluminescent microparticle immunoassay (CMIA), molecular tests such as reverse transcription polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR) performed better in terms of sensitivity and specificity. Additionally, the area under the curve restricted to the false-positive rates (AUCFPR) of 0.984 obtained by the antiviral neutralization bioassay (ANB) diagnostic test revealed significant potential for the identification of COVID-19. It has been established that the various diagnostic tests have been effectively adapted for the detection of SARS-CoV-2; nevertheless, their performance still must be enhanced to contain potential COVID-19 outbreaks, which will also help contain potential infectious agent outbreaks in the future.

Computer-aided drug design approaches applied to screen natural product's structural analogs targeting arginase in Leishmania spp.

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions by MM-GBSA and FEP methods. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

The Potential of Xylooligosaccharides as Prebiotics and Their Sustainable Production from Agro-Industrial by-Products.

In recent years, concerns about a good-quality diet have increased. Food supplements such as prebiotics have great nutritional and health benefits. Within the diverse range of prebiotics, xylooligosaccharides (XOs) show high potential, presenting exceptional properties for the prevention of systemic disorders. XOs can be found in different natural sources; however, their production is limited. Lignocellulosic biomasses present a high potential as a source of raw material for the production of XOs, making the agro-industrial by-products the perfect candidates for production on an industrial scale. However, these biomasses require the application of physicochemical pretreatments to obtain XOs. Different pretreatment methodologies are discussed in terms of increasing the production of XOs and limiting the coproduction of toxic compounds. The advance in new technologies for XOs production could decrease their real cost (USD 25-50/kg) on an industrial scale and would increase the volume of market transactions in the prebiotic sector (USD 4.5 billion). In this sense, new patents and innovations are being strategically developed to expand the use of XOs as daily prebiotics.

Co-occurring pathogenic variants in 6q27 associated with dementia spectrum disorders in a Peruvian family.

Evidence suggests that there may be racial differences in risk factors associated with the development of Alzheimer's disease and related dementia (ADRD). We used whole-genome sequencing analysis and identified a novel combination of three pathogenic variants in the heterozygous state (UNC93A: rs7739897 and WDR27: rs61740334; rs3800544) in a Peruvian family with a strong clinical history of ADRD. Notably, the combination of these variants was present in two generations of affected individuals but absent in healthy members of the family. In silico and in vitro studies have provided insights into the pathogenicity of these variants. These studies predict that the loss of function of the mutant UNC93A and WDR27 proteins induced dramatic changes in the global transcriptomic signature of brain cells, including neurons, astrocytes, and especially pericytes and vascular smooth muscle cells, indicating that the combination of these three variants may affect the neurovascular unit. In addition, known key molecular pathways associated with dementia spectrum disorders were enriched in brain cells with low levels of UNC93A and WDR27. Our findings have thus identified a genetic risk factor for familial dementia in a Peruvian family with an Amerindian ancestral background.

A new species of Andean lizard, Proctoporus (Gymnophthalmidae: Cercosaurinae), from the highland of Parque Nacional Otishi in Peru.

The gymnophthalmid Andean lizards of the genus Proctoporus (Gymnophthalmidae, Cercosaurinae) are semifossorial species that inhabit the montane forests, inter-Andean valley, and humid grasslands across the Cordillera de los Andes from Peru to Argentina. The distribution range of Proctoporus is discontinuous, with many places lacking herpetological surveys. Here, based on morphological data, we describe a new species of Proctoporus from a remote location on a mountaintop north of the Cordillera de Vilcabamba in southeastern Peru. The new species is readily distinguished from all other species of Proctoporus by the presence of three anterior infralabials, three rows of pregular scales and the absence of enlarged pregular scales. With this new species, the species diversity has increased to 19 since 18 species have previously been identified.

Bioprospecting lipid-producing microorganisms: From metagenomic-assisted isolation techniques to industrial application and innovations.

Traditionally, lipid-producing microorganisms have been obtained via conventional bioprospecting based on isolation and screening techniques, demanding time and effort. Thus, high-throughput sequencing combined with conventional microbiological approaches has emerged as an advanced and rapid strategy for recovering novel oleaginous microorganisms from target environments. This review highlights recent developments in lipid-producing microorganism bioprospecting, following (i) from traditional cultivation techniques to state-of-the-art metagenomics approaches; (ii) related topics on workflow, next-generation sequencing platforms, and knowledge bioinformatics; and (iii) biotechnological potential of the production of docosahexaenoic acid (DHA) by Aurantiochytrium limacinum, arachidonic acid (ARA) by Mortierella alpina and biodiesel by Rhodosporidium toruloides. These three species have been shown to be highly promising and studied in research articles, patents and commercialized products. Trends, innovations and future perspectives of these microorganisms are also addressed. Thus, these microbial lipids allow the development of food, feed and biofuels as alternative solutions to animal and vegetable oils.

Alzheimer's Disease: A Silent Pandemic - A Systematic Review on the Situation and Patent Landscape of the Diagnosis.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment, tau protein deposits, and amyloid beta plaques. AD impacted 44 million people in 2016, and it is estimated to affect 100 million people by 2050. AD is disregarded as a pandemic compared with other diseases. To date, there is no effective treatment or diagnosis. OBJECTIVE: We aimed to discuss the current tools used to diagnose COVID-19, point out their potential to be adapted for AD diagnosis, and review the landscape of existing patents in the AD field and future perspectives for AD diagnosis. METHODS: We carried out a scientific screening following a research strategy in PubMed; Web of Science; the Derwent Innovation Index; the KCI-Korean Journal Database; Sci- ELO; the Russian Science Citation index; and the CDerwent, EDerwent, and MDerwent index databases. RESULTS: A total of 326 from 6,446 articles about AD and 376 from 4,595 articles about COVID-19 were analyzed. Of these, AD patents were focused on biomarkers and neuroimaging with no accurate, validated diagnostic methods, and only 7% of kit development patents were found. In comparison, COVID-19 patents were 60% about kit development for diagnosis; they are highly accurate and are now commercialized. CONCLUSION: AD is still neglected and not recognized as a pandemic that affects the people and economies of all nations. There is a gap in the development of AD diagnostic tools that could be filled if the interest and effort that has been invested in tackling the COVID-19 emergency could also be applied for innovation.

In vitro cytotoxic effect of a chitin-like polysaccharide produced by Mortierella alpina on adrenocortical carcinoma cells H295R, and its use as mitotane adjuvant.

This study presents an in vitro evaluation of the antitumor potential of a chitin-like exopolysaccharide (EPS, produced by Mortierella alpina) on Adrenocortical carcinoma cells (ACC) compared to mitotane, a commercial drug commonly used in ACC treatment, and known for its side effects. Techniques of cellular viability determination such as MTT and fluorescence were used to measure the cytotoxic effects of the EPS and mitotane in tumoral cells (H295R) and non-tumoral cells (VERO), observing high cytotoxicity of mitotane and a 10% superior pro-apoptotic effect of the EPS compared to mitotane (p < 0.05). The cytotoxic effect of the EPS was similar to the effect of 50 µM mitotane on tumoral cells (p < 0.05). A decrement of the lysosomal volume was also noted in tumoral cells treated with the EPS. To enhance the antitumor effect, a combination of mitotane at a lower dosage and the EPS (as adjuvant) was also tested, showing a slight improvement of the cytotoxicity effect on tumoral cells. Therefore, the results indicate a cytotoxic effect of the EPS produced by Mortierella alpina on adrenocortical carcinoma, and a possible application in biomedical formulations or additional treatments.

Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease.

Despite the emerging evidence implying early vascular contributions to neurodegenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease (AD) is still not well understood. Herein, we show that VSMCs in brains of patients with AD and animal models of the disease are deficient in multiple VSMC contractile markers which correlated with Tau accumulation in brain arterioles. Ex vivo and in vitro experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205, and S262. We also observed that VSMC dysfunction occurred in an age-dependent manner and that expression of Sm22α protein was inversely correlated with CD68 and Tau expression in brain arterioles of the 3xTg-AD and 5xFAD mice. Together, these findings further support the contribution of dysfunctional VSMCs in AD pathogenesis and nominate VSMCs as a potential therapeutic target in AD.

Development of a Web Database System for a Comprehensive Hypertension Management Program in the Primary Health Care Setting of Urban Areas of Peru.

OBJECTIVES: The objective of this case report is to introduce the development process, structure, characteristics, and effectiveness of the web database (DB) system developed for the hypertension management program in the primary health care setting in the low-income urban areas of Peru. METHODS: A Korean research team cooperated with a Peruvian IT startup company to develop a web DB system to improve the data management of the hypertension management program. The entire web application infrastructure was hosted using the Amazon Web Service. Two different web platforms were established for the user groups of health workers and researchers (program managers). RESULTS: A total of 2,827 program participants were registered in the web DB system until December 2017. Health professionals can input the participant data while providing consultation to the program participants, and the data is accumulated in the web DB in real time. Input errors or data loss is prevented by setting restrictions in the data entry system. During the 4-year project period, 7,696 hours of working time and USD 39,536.48 for data management were saved as the result of web DB system utilization. CONCLUSIONS: The developed web DB system contributed to improve the health condition of the health program participants by providing necessary information to the health professionals at the right time. This case report could be a reference for other researcher to develop web databases for their own context, especially in developing countries.

Epidemiologia de la leucemia neonatal en Bolivia / Epidemiology of neonatal leukemia in Bolivia

Introducción. La leucemia neonatal se presenta durante las cuatro primeras semanas de vida extrauterina, corresponde al 1% de todas las leucemias pediátricas. Se caracteriza por leucemogénesis en útero y está relacionada con la genotoxicidad y el medio ambiente contaminado. La leucemia mieloide aguda representa la gran mayoría de los casos (60%), las alteraciones cromosómicas afectan a la región 11q23. La infiltración cutánea leucémica, la hepatoesplenomegalia y la leucocitosis mayor a 100.000/ul son signos comunes en esta enfermedad. Objetivo. Determinar las características epidemiológicas de la leucemia neonatal en Bolivia. Material y métodos. Estudio descriptivo retrospectivo de leucemias neonatales diagnosticadas entre 2007 y 2023. Se recolectó datos epidemiológicos concernientes a características clínicas, características morfológicas e immunofenotípicas, resultados de laboratorio correspondientes al momento del diagnóstico y seguimiento, así como, la radicatoria de la madre durante la gestación. Resultados. Se evidenció 13 casos, la edad media neonatal fue 20 días y mayor incidencia en neonatos varones (n=9, 69%). La LMA (9 casos, 69 %) fue el tipo de leucemia más frecuente (subtipo preponderante LMA M7), seguida de la LLA-B (n=4). 7 casos fueron procedentes de Santa Cruz (54 %), 3 de Cochabamba (23 %), sucesivamente La Paz, Beni y Chuquisaca con un caso cada uno (23 %). Leucocitosis media 106.000/ul, hemoglobina media 13,2 g/dl y plaquetas 209.000/ul fueron características laboratoriales. Conclusiones. La incidencia de leucemia neonatal en Santa Cruz y Cochabamba constituye un interés de salud pública, lo que demanda escudriñar sobre factores de riesgo relacionados con su etiología y el impacto de la contaminación del medio ambiente en esas regiones.

Introduction. Neonatal leukemia occurs during the first four weeks after birth, corresponding to 1% of all pediatric leukemias. It is characterized byleukemogenesis in the uterus, which is related to genotoxicity and polluted environment. Acute myeloid leukemia representas the vast majority of cases (60%), chromosomal alterations concerning 11q23 region. Common signs involve leukemia cutis, hepatosplenomegaly and leukocytosis higher than 100,000/ul. Objective. To determine the epidemiological characteristics of neonatal leukemia in Bolivia. Material and methods. Retrospective descriptive study of neonatal leukemias diagnosed between 2007 and 2023. Epidemiological data regarding clinical characteristics, morphological and immunophenotypic features, laboratory results at diagnosis and follow-up, as well as, residency of the mother during pregnancy were collected. Results. A total of 13 cases were evidenced, mean neonatal age was 20 days, with a higher incidence in male neonates (n=9, 69%). AML (9 cases, 69%) was the most common type of leukemia (mainly AML M7 subtype), followed by B-ALL (n=4). 7 cases were from Santa Cruz (54%), 3 from Cochabamba (23%), consecutively La Paz, Beni and Chuquisaca with 1 case each (23%). Laboratory characteristics displayed mean leukocytosis of106,000/ul, mean Hb 13,2 g/dl and platelets 209.000/ ul. Conclusions. The incidence of neonatal leukemia in Santa Cruz and Cochabamba stands a public health interest, which requires scrutinizing risk factors related to its etiology and the impact of environmental pollution in those region.

Estratificacion de riesgo y pronostico de las eritrocitosis patologicas en la altura / Risk stratification and prognosis of pathological erythrocytoses at altitude

Introducción. Las eritrocitosis patológicas en la altura afectan al 10 % de la población constituyéndose una causa importante de morbilidad por enfermedades no transmisibles. Suscita emergente categorizar la severidad de estas eritrocitosis para estimar su evolución y tratamientos adecuados. Objetivo. Estratificar el riesgo de las eritrocitosis patológicas en la altura considerando parámetros de severidad que sean de utilidad clínica en el pronóstico y tratamiento. Material y métodos. Estudio transversal retrospectivo de 283 historias clínicas de pacientes con eritrocitosis patológica de altura (EPA) o eritrocitosis secundaria (ES), residentes en altura (>3600 m s. n. m) y diagnosticados entre gestiones 2000 a 2021. Se identificó características clínico-laboratoriales diferenciales respecto del diagnóstico, respuesta al tratamiento y evolución de pacientes. Se planteó 3 niveles de estratificación de riesgo (bajo, intermedio, alto) considerando variaciones en síntomas de hiperviscosidad, eritropoyetina, complicaciones y comorbilidades. Resultados. 194 pacientes correspondieron al grupo de riesgo bajo, 67 al riesgo intermedio y 22 al riesgo alto. Riesgo bajo conllevó Epo 30 mUI/ml (30-100 mUI/ml), tratamiento con atorvastatina-aspirina, respuestas parciales y pronóstico regular, concerniendo pacientes con ES asociada a patologías pulmonares leves. Riesgo alto reflejó Epo >100 mUI/ml, inclusión de hidroxiurea al tratamiento con atorvastatina, menor respuesta y pronóstico desfavorable, incumbiendo pacientes >60 años con ES asociada a patologías pulmonares crónicas severas o complicaciones por eritrocitosis. Conclusiones. Contar con niveles de riesgo para las eritrocitosis patológicas permite conjeturar su pronóstico y optimizar decisiones terapéuticas.

Introduction. Pathological erythrocytoses at altitude affect 10% of the population, representing an important cause of morbidity from non-communicable diseases. Categorizing the severity of such erythrocytoses to estimate their evolution and suitable treatments becomes emergent. Objective. To stratify the risk of the pathological erythrocytoses at high altitude considering severity parameters useful for prognosis and treatment. Material and methods. Retrospective cross-sectional study that included 283 medical records of patients with Chronic Mountain Sickness-erythrocytosis (CMS-e) or Secondary Erythrocytosis (SE), inhabitants at high altitude (>3600 m a. s. l.) diagnosed between 2000 to 2021. Differential clinical-laboratory characteristics regarding the diagnosis, response to treatment and evolution of patients were identified. Three risk groups (low, intermediate, high) were raised, considering variations about hyperviscosity symptoms, erythropoietin levels, complications, and comorbidities. Results. 194 patients corresponded to the low-risk group, 67 to the intermediaterisk and 22 to the high-risk. Low-risk group involved Epo 30 mIU/ml (30-100 mIU/ ml), treatment with atorvastatin-aspirin, partial responses and favorable prognosis, concerning patients with SE attributed to mild lung diseases. High-risk reflected Epo >100 mIU/ml, inclusion of hydroxyurea to the treatment with atorvastatin, poor response and unfavorable prognosis, involving patients >60 years of age with SE attributed to severe and chronic lung diseases or complications due to erythrocytosis. Conclusion. Counting on a risk stratification for pathological erythrocytosis at high altitude allows to assess the prognosis and optimize therapeutic decisions.

Variaciones fenotípicas relacionadas a respuestas hipóxicas entre andinos a distintas altitudes / Phenotypic variations related to hypoxic responses among Andeans at different altitudes

Introducción. La adaptación a grandes altitudes implica cambios evolutivos que conllevan respuestas adaptativas, como a la hipoxia. Los andinos desarrollaron fenotipos eritroides diferentes en relación con otras poblaciones a gran altitud que pueden variar dependiendo la altitud. Objetivo. Determinar las variaciones fenotípicas de hemoglobina (Hb), saturación de oxígeno (SpO2), P50 y lactato en andinos bolivianos con radicatorias entre 400, 4000 y 5000 msnm. Material y métodos. Estudio descriptivo transversal de tipo prospectivo. Se recolectó sangre venosa periférica de andinos bolivianos (n=124) nacidos a 4000 m, pero con radicatoria en altitudes diferentes (400 m, 4000 m, 5000 m), así como de aquellos con eritrocitosis patológicas. Adicionalmente, se recolectó muestras de europeos residentes a 4000 m (n=11). Se realizó estudios de hemograma, oximetría y gasometría. La P50 fue calculada con fórmula de Lichtman. Resultados. Los andinos sanos, comparados entre distintas altitudes, reflejaron aumento de Hb al ser mayor la altitud (p: 0,001), empero disminución de SpO2 (p: 0,001) y P50 (p: 0,001); sin variaciones en lactato. Los europeos a 4000 m, en relación con andinos a la misma altitud, presentaron Hb incrementada (p: 0,01), SpO2 y P50 sin variaciones, pero lactato significativamente aumentado (p: 0,001). Los pacientes con eritrocitosis comparados con sujetos sanos, a 4000 m y 5000 m respectivamente, presentaron Hb aumentada (p: 0,001); SpO2 disminuida (p: 0,001); P50 sin variaciones, pero lactato incrementado (p: 0,01). El lactato elevado en sujetos a 5000 m con eritrocitosis fue llamativo (1,7 mmol/L). Conclusiones. Las variaciones fenotípicas observadas entre andinos en diferentes altitudes constituyen una expresión de una adaptación parcial a la altura.

Introduction. Human adaptation to high altitude involves evolutionary changes leading adaptive responses, such as to hypoxia. Andeans developed different erythroid phenotypes in relation to other populations at high altitude, which can vary depending on the altitude. Objective. To determine the phenotypic variations of hemoglobin (Hb), oxygen saturation (SpO2), P50 and lactate in Bolivian Andeans residing between 400, 4000 or 5000 masl. Material and methods. Prospective cross-sectional descriptive study. Peripheral venous blood from Bolivian Andeans (n=124) born at 4000 m, but residing at different altitudes (400 m, 4000 m, 5000 m), likewise from those with pathological erythrocytosis were collected. Additionally, samples from Europeans residing at 4000 m (n=11) were collected. CBC, oximetry and blood gas studies were performed. P50 was calculated using the Lichtman formula. Results. Healthy Andeans, compared between different altitudes, reflected an increased Hb (p: 0.001), but a decreased SpO2 (p: 0.001) and P50 (p: 0.001) as the altitude was higher; without variations in lactate. Europeans at 4000 m, related to Andeans at the same altitude, presented increased Hb (p: 0.01), SpO2 and P50 without variations, but significantly increased lactate (p: 0.001). Patients with erythrocytosis compared to healthy subjects, at 4000 m and 5000 m respectively, depicted increased Hb (p: 0.001); decreased SpO2 (p: 0.001); P50 without changes, but increased lactate (p: 0.01). Increased lactate in subjects with erythrocytosis at 5000 m was remarkable (1.7 mmol/L). Conclusion. The phenotypic variations observed among Andeans residing at different altitudes constitute an expression of partial adaptation to altitude.