Lactate-carried Mitochondrial Energy Overflow.

We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate.

Flow cytometry protocol for GLUT4-myc detection on cell surfaces.

Insulin and muscle contraction trigger GLUT4 translocation to the plasma membrane, which increases glucose uptake by muscle cells. Insulin resistance and Type 2 diabetes are the result of impaired GLUT4 translocation. Quantifying GLUT4 translocation is essential for comprehending the intricacies of both physiological and pathophysiological processes involved in glucose metabolism. The most commonly used methods for measuring GLUT4 translocation are the ELISA-type assay and the immunofluorescence assay. While some reports suggest that flow cytometry could be useful in quantifying GLUT4 translocation, this technique is not frequently used. Much of our current understanding of the regulation of GLUT4 has been based on experiments using the rat myoblast cell line (L6 cell) which expresses GLUT4 with a myc epitope on the exofacial loop. In the present study, we use the L6-GLUT4myc cell line to develop a flow cytometry-based approach to detect GLUT4 translocation. Flow cytometry offers the advantages of both immunofluorescence and ELISA-based assays. It allows easy identification of separate cell populations in the sample, similar to immunofluorescence, while providing results based on a population-level analysis of multiple individual cells, like an ELISA-based assay. Our results demonstrate a 0.6-fold increase with insulin stimulation compared with basal conditions. Finally, flow cytometry consistently yielded results across different experiments and exhibited sensitivity under the tested conditions.

[Concordance between essential medicines lists and diabetes guidelines in Latin America and the CaribbeanConcordância entre as listas de medicamentos essenciais e diretrizes para diabetes na América Latina e no Caribe]. / Concordancia entre las listas de medicamentos esenciales y las guías para diabetes en América Latina y el Caribe.

Objective: Conduct an analysis to determine the existence and updating of national essential medicines lists (EMLs) and clinical practice guidelines (CPGs) for the treatment of diabetes in Latin America and the Caribbean (LAC); and compare the medicines included in each country's list and guidelines both with each other and with those of the World Health Organization (WHO). Methods: Cross-sectional study. EMLs and CPGs for diabetes were found on the websites of the Pan American Health Organization and national health authorities. Medicines were noted and analyzed according to pharmacological group, based on the fourth level of nomenclature of the Anatomical Therapeutic Chemical (ATC) classification system. F1 scoring was used to assess the proximity of EMLs to the WHO Model List of Essential Medicines (MLEM). Results: Of the total number of countries, 87.2% have EMLs, and 91% have CPGs (78% and 45% updated in the last five years, respectively). Compared to the six hypoglycemic groups of the MLEM, the EMLs had a median (range) of 6 (4-13) and an F1 score of 0.80; This indicates proper alignment. CPGs had a median (range) of 12 (1-12) hypoglycemic drugs compared to eight in the WHO guidelines. CPGs had a median of 15 more drugs than their respective EMLs. Conclusions: While most LAC countries have EMLs and CPGs for diabetes, the lack of concordance among them limits their effectiveness. It is necessary to align the processes and criteria for the development of these two tools for policymaking on medicines.

Objetivos: Analisar a existência e a atualização das listas nacionais de medicamentos (LNMs) e guias de prática clínica (GPCs) para o tratamento do diabetes na América Latina e no Caribe (ALC). Comparar os medicamentos incluídos nas listas e nas diretrizes de cada país entre si e com as da Organização Mundial da Saúde (OMS). Métodos: Estudo transversal. Foram identificadas LMNs e GPCs para o diabetes nos sites da Organização Pan-Americana da Saúde e das autoridades sanitárias nacionais. Os medicamentos foram pesquisados e analisados por grupo farmacológico de acordo com o quarto nível da classificação ATC. A pontuação F1 foi utilizada para avaliar o grau de proximidade das LMNs com a lista-modelo de medicamentos essenciais (LMME) da OMS. Resultados: Do total de países, 87,2% dispõem de uma LNM e 91%, de GPCs (78% e 45%, respectivamente, atualizadas nos últimos 5 anos). Em comparação com os seis grupos de agentes hipoglicemiantes da LMME, as LMNs tinham uma mediana (intervalo) de 6 (4 a 13) e uma pontuação F1 de 0,80, o que indica uma conformidade adequada. As GPCs tinham uma mediana (intervalo) de 12 (1 a 12) agentes hipoglicemiantes, em comparação com 8 nos guias da OMS. As GPCs tinham uma mediana de 15 medicamentos a mais do que as respectivas LNMs. Conclusões: Embora a maioria dos países da América Latina e do Caribe disponha de LNMs e GPCs para o diabetes, a falta de concordância entre elas limita sua eficácia. É necessário alinhar os processos e os critérios de desenvolvimento dessas duas ferramentas da política de medicamentos.

Concordancia entre las listas de medicamentos esenciales y las guías para diabetes en América Latina y el Caribe / Concordance between essential medicines lists and diabetes guidelines in Latin America and the Caribbean / Concordância entre as listas de medicamentos essenciais e diretrizes para diabetes na América Latina e no Caribe

[RESUMEN]. Objetivo. Analizar la existencia y actualización de las listas de medicamentos nacionales (LMN) y guías de práctica clínica (GPC) para el tratamiento de la diabetes en América Latina y el Caribe (ALC). Comparar los fármacos incluidos en las listas y guías de cada país, entre sí y con los de la Organización Mundial de la Salud (OMS). Métodos. Estudio de corte transversal. Se identificaron las LMN y GPC para diabetes en los sitios web de la Organización Panamericana de la Salud y de las autoridades sanitarias nacionales. Se relevaron los fármacos y se analizaron por grupo farmacológico según el cuarto nivel de la nomenclatura ATC. Se utilizó el puntaje F1 para evaluar la proximidad de las LMN con la lista modelo de medicamentos esenciales (LMME) de la OMS. Resultados. Del total de países, 87,2% cuentan con LMN, y 91% con GPC (78% y 45% actualizadas en los últimos 5 años, respectivamente). En comparación con los 6 grupos de hipoglucemiantes de la LMME, las LMN tenían una mediana (rango) de 6 (4-13) y un puntaje F1 de 0,80; esto indica una consonancia adecuada. Las GPC tenían una mediana (rango) de 12 (1-12) hipoglucemiantes frente a los 8 de las guías de la OMS. Las GPC tuvieron una mediana de 15 fármacos más que las respectivas LMN. Conclusiones. Si bien la mayoría de los países de ALC cuentan con LMN y GPC para diabetes, la falta de concordancia entre ellas limita su eficacia. Es necesario alinear los procesos y criterios de elaboración de estas dos herramientas de la política de medicamentos.

[ABSTRACT]. Objective. Conduct an analysis to determine the existence and updating of national essential medicines lists (EMLs) and clinical practice guidelines (CPGs) for the treatment of diabetes in Latin America and the Carib- bean (LAC); and compare the medicines included in each country's list and guidelines both with each other and with those of the World Health Organization (WHO). Methods. Cross-sectional study. EMLs and CPGs for diabetes were found on the websites of the Pan Amer- ican Health Organization and national health authorities. Medicines were noted and analyzed according to pharmacological group, based on the fourth level of nomenclature of the Anatomical Therapeutic Chemical (ATC) classification system. F1 scoring was used to assess the proximity of EMLs to the WHO Model List of Essential Medicines (MLEM). Results. Of the total number of countries, 87.2% have EMLs, and 91% have CPGs (78% and 45% updated in the last five years, respectively). Compared to the six hypoglycemic groups of the MLEM, the EMLs had a median (range) of 6 (4–13) and an F1 score of 0.80; This indicates proper alignment. CPGs had a median (range) of 12 (1–12) hypoglycemic drugs compared to eight in the WHO guidelines. CPGs had a median of 15 more drugs than their respective EMLs. Conclusions. While most LAC countries have EMLs and CPGs for diabetes, the lack of concordance among them limits their effectiveness. It is necessary to align the processes and criteria for the development of these two tools for policymaking on medicines.

[RESUMO]. Objetivos. Analisar a existência e a atualização das listas nacionais de medicamentos (LNMs) e guias de prática clínica (GPCs) para o tratamento do diabetes na América Latina e no Caribe (ALC). Comparar os medicamentos incluídos nas listas e nas diretrizes de cada país entre si e com as da Organização Mundial da Saúde (OMS). Métodos. Estudo transversal. Foram identificadas LMNs e GPCs para o diabetes nos sites da Organização Pan-Americana da Saúde e das autoridades sanitárias nacionais. Os medicamentos foram pesquisados e analisados por grupo farmacológico de acordo com o quarto nível da classificação ATC. A pontuação F1 foi utilizada para avaliar o grau de proximidade das LMNs com a lista-modelo de medicamentos essenciais (LMME) da OMS. Resultados. Do total de países, 87,2% dispõem de uma LNM e 91%, de GPCs (78% e 45%, respectivamente, atualizadas nos últimos 5 anos). Em comparação com os seis grupos de agentes hipoglicemiantes da LMME, as LMNs tinham uma mediana (intervalo) de 6 (4 a 13) e uma pontuação F1 de 0,80, o que indica uma con- formidade adequada. As GPCs tinham uma mediana (intervalo) de 12 (1 a 12) agentes hipoglicemiantes, em comparação com 8 nos guias da OMS. As GPCs tinham uma mediana de 15 medicamentos a mais do que as respectivas LNMs. Conclusões. Embora a maioria dos países da América Latina e do Caribe disponha de LNMs e GPCs para o diabetes, a falta de concordância entre elas limita sua eficácia. É necessário alinhar os processos e os critérios de desenvolvimento dessas duas ferramentas da política de medicamentos.

Concordancia entre las listas de medicamentos esenciales y las guías para diabetes en América Latina y el Caribe / Concordance between essential medicines lists and diabetes guidelines in Latin America and the Caribbean / Concordância entre as listas de medicamentos essenciais e diretrizes para diabetes na América Latina e no Caribe

RESUMEN Objetivo. Analizar la existencia y actualización de las listas de medicamentos nacionales (LMN) y guías de práctica clínica (GPC) para el tratamiento de la diabetes en América Latina y el Caribe (ALC). Comparar los fármacos incluidos en las listas y guías de cada país, entre sí y con los de la Organización Mundial de la Salud (OMS). Métodos. Estudio de corte transversal. Se identificaron las LMN y GPC para diabetes en los sitios web de la Organización Panamericana de la Salud y de las autoridades sanitarias nacionales. Se relevaron los fármacos y se analizaron por grupo farmacológico según el cuarto nivel de la nomenclatura ATC. Se utilizó el puntaje F1 para evaluar la proximidad de las LMN con la lista modelo de medicamentos esenciales (LMME) de la OMS. Resultados. Del total de países, 87,2% cuentan con LMN, y 91% con GPC (78% y 45% actualizadas en los últimos 5 años, respectivamente). En comparación con los 6 grupos de hipoglucemiantes de la LMME, las LMN tenían una mediana (rango) de 6 (4-13) y un puntaje F1 de 0,80; esto indica una consonancia adecuada. Las GPC tenían una mediana (rango) de 12 (1-12) hipoglucemiantes frente a los 8 de las guías de la OMS. Las GPC tuvieron una mediana de 15 fármacos más que las respectivas LMN. Conclusiones. Si bien la mayoría de los países de ALC cuentan con LMN y GPC para diabetes, la falta de concordancia entre ellas limita su eficacia. Es necesario alinear los procesos y criterios de elaboración de estas dos herramientas de la política de medicamentos.

ABSTRACT Objective. Conduct an analysis to determine the existence and updating of national essential medicines lists (EMLs) and clinical practice guidelines (CPGs) for the treatment of diabetes in Latin America and the Caribbean (LAC); and compare the medicines included in each country's list and guidelines both with each other and with those of the World Health Organization (WHO). Methods. Cross-sectional study. EMLs and CPGs for diabetes were found on the websites of the Pan American Health Organization and national health authorities. Medicines were noted and analyzed according to pharmacological group, based on the fourth level of nomenclature of the Anatomical Therapeutic Chemical (ATC) classification system. F1 scoring was used to assess the proximity of EMLs to the WHO Model List of Essential Medicines (MLEM). Results. Of the total number of countries, 87.2% have EMLs, and 91% have CPGs (78% and 45% updated in the last five years, respectively). Compared to the six hypoglycemic groups of the MLEM, the EMLs had a median (range) of 6 (4-13) and an F1 score of 0.80; This indicates proper alignment. CPGs had a median (range) of 12 (1-12) hypoglycemic drugs compared to eight in the WHO guidelines. CPGs had a median of 15 more drugs than their respective EMLs. Conclusions. While most LAC countries have EMLs and CPGs for diabetes, the lack of concordance among them limits their effectiveness. It is necessary to align the processes and criteria for the development of these two tools for policymaking on medicines.

RESUMO Objetivos. Analisar a existência e a atualização das listas nacionais de medicamentos (LNMs) e guias de prática clínica (GPCs) para o tratamento do diabetes na América Latina e no Caribe (ALC). Comparar os medicamentos incluídos nas listas e nas diretrizes de cada país entre si e com as da Organização Mundial da Saúde (OMS). Métodos. Estudo transversal. Foram identificadas LMNs e GPCs para o diabetes nos sites da Organização Pan-Americana da Saúde e das autoridades sanitárias nacionais. Os medicamentos foram pesquisados e analisados por grupo farmacológico de acordo com o quarto nível da classificação ATC. A pontuação F1 foi utilizada para avaliar o grau de proximidade das LMNs com a lista-modelo de medicamentos essenciais (LMME) da OMS. Resultados. Do total de países, 87,2% dispõem de uma LNM e 91%, de GPCs (78% e 45%, respectivamente, atualizadas nos últimos 5 anos). Em comparação com os seis grupos de agentes hipoglicemiantes da LMME, as LMNs tinham uma mediana (intervalo) de 6 (4 a 13) e uma pontuação F1 de 0,80, o que indica uma conformidade adequada. As GPCs tinham uma mediana (intervalo) de 12 (1 a 12) agentes hipoglicemiantes, em comparação com 8 nos guias da OMS. As GPCs tinham uma mediana de 15 medicamentos a mais do que as respectivas LNMs. Conclusões. Embora a maioria dos países da América Latina e do Caribe disponha de LNMs e GPCs para o diabetes, a falta de concordância entre elas limita sua eficácia. É necessário alinhar os processos e os critérios de desenvolvimento dessas duas ferramentas da política de medicamentos.

Drosophila nasuta (Diptera, Drosophilidae) in Brazil: a decade of invasion and occupation of more than half of the country.

As a result of human activities and natural dispersal, exotic species can be brought to new areas, where they become established and spread, becoming invaders. These species are responsible for the loss of biodiversity and cause ecosystemic harm throughout the world. In this paper, we report the rapid, broad geographic expansion of the invasive fly Drosophila nasuta in Brazil. An 84% increase was found in its area of occupation in the country compared to previous studies. The present data reveal its arrival to the Pantanal wetlands in a location more than one thousand kilometers from the closest previous record in the Cerrado biome. We present the first record of D. nasuta in the Atlantic Forest in the states of Paraíba and Bahia. We report its introduction in the Amazon Forest in the state of Amazonas approximately 700 kilometers from previous records. The relative abundance of D. nasuta in this biome increased fivefold in comparison to a previous study. In the first decade of invasion in Brazil, D. nasuta has already colonized more than half of the country. The present data reveal its invasive potential and underscore the importance of following up the possible negative effects of this biological invasion.

Activity of domain III-specific antibodies in early convalescence: A case study.

The Dengue virus complex (DENV), formed by four serotypes, constitutes the most important arbovirus affecting humans. The structural domain III of their envelope protein (DIII) elicits strongly neutralizing serotype-specific antibodies. Contrasting results have been obtained regarding their role in the serum neutralizing activity of infected patients. We used a DENV immune serum from a secondary infection to examine the impact of characterizing the anti-DIII antibody response after affinity purification with recombinant DIII proteins to eliminate potential interferences from the interactions with human plasma proteins and other anti-DENV antibodies. Total anti-DENV IgG repertoire and anti-DIIIE antibodies were compared in functionality. In early convalescence, reactivity of anti-DIII antibodies is serotype specific and exhibits the strongest reactivity with infecting serotypes. Purification of anti-DIII antibodies emphasizes the reactivity profile as compared to total IgG fraction and serum. Serotype-specificity of the virus neutralization activity correlated with the apparent kD of the binding to recombinant DIIIs.

Estimation of Reference Evapotranspiration in a Semi-Arid Region of Mexico.

Reference evapotranspiration (ET0) is the first step in calculating crop irrigation demand, and numerous methods have been proposed to estimate this parameter. FAO-56 Penman-Monteith (PM) is the only standard method for defining and calculating ET0. However, it requires radiation, air temperature, atmospheric humidity, and wind speed data, limiting its application in regions where these data are unavailable; therefore, new alternatives are required. This study compared the accuracy of ET0 calculated with the Blaney-Criddle (BC) and Hargreaves-Samani (HS) methods versus PM using information from an automated weather station (AWS) and the NASA-POWER platform (NP) for different periods. The information collected corresponds to Module XII of the Lagunera Region Irrigation District 017, a semi-arid region in the North of Mexico. The HS method underestimated the reference evapotranspiration (ET0) by 5.5% compared to the PM method considering the total ET0 of the study period (26 February to 9 August 2021) and yielded the best fit in the different evaluation periods (daily, 5-day mean, and 5-day cumulative); the latter showed the best values of inferential parameters. The information about maximum and minimum temperatures from the NP platform was suitable for estimating ET0 using the HS equation. This data source is a suitable alternative, particularly in semi-arid regions with limited climatological data from weather stations.

Late Periprosthetic Femoral Stress Fracture Associated with Extra-articular Deformity in a Patient with Fibrous Dysplasia: A Case Report.

CASE: In the setting of a total hip arthroplasty performed in a patient with a proximal femoral deformity, atraumatic periprosthetic femoral stress fracture may arise as a complication. We report a rare case of a late periprosthetic femoral stress fracture around a cemented stem in a patient with a history of fibrous dysplasia of the proximal femur. After a 10-year uneventful period, the patient complained about a subtle, subacute pain in his left thigh induced by exercise but not with daily axial load. Diagnosis of a nondisplaced, incomplete (i.e., only compromising the lateral femoral cortex) periprosthetic femoral stress fracture was made with plain radiographs, blood work, and bone scintigraphy. Surgical treatment consisted of a minimally invasive plate osteosynthesis bridging the femoral deformity plus percutaneous osteoperiosteal decortication. At 5-year follow-up, the patient was asymptomatic with full return to physical activity, with radiographs evidencing callus formation. CONCLUSION: Stress fractures around well-fixed femoral stems, while infrequent, should be addressed in patients with a history of severe proximal femur deformity experiencing atraumatic thigh pain.

Intraoperative unfractionated heparin before femoral component cementation should be avoided in femoral neck fracture treated with hybrid total hip arthroplasty.

PURPOSE: To compare the incidence of perioperative thromboembolic events in femoral neck fracture (FNF) patients treated with hybrid total hip arthroplasty (THA) with intraoperative unfractionated heparin (UFH) versus a control group without intraoperative UFH before femoral component cementation. METHODS: We compared 139 cases without UFH (group A) versus 134 who received 10 UI/kg UFH (group B). Indication of UFH before cementation depended on the preferences of the anaesthesiologists in each case. We assessed intraoperative bone cement implantation syndrome (BCIS) and 30-day thromboembolic events, and 90-day and 1-year mortality. BCIS was classified as per Donaldson et al.'s classification according to the degree of hypotension, arterial desaturation or loss of consciousness. RESULTS: BCIS was observed in 51 (18%) cases, including 37 (13%) grade 1 and 14 (5%) grade 2. Forty-seven BCISs (35%) were observed in group B and 4 (3%) in group A (p < 0.001). Multivariate regression showed that intraoperative UFH (OR = 18, CI 95% 6-52) and consumption of oral anticoagulants (OR = 3.3, CI 95% 1-10) increased the risk of BCIS. Five patients further developed a 30-day pulmonary embolism in group B, while 2 presented this complication in group A (p = 0.231). No association between BCIS and 30-day thromboembolic events was found (p = 0.62). 90-day (1% each, p = 0.98) and 1-year (2% vs. 3%, p = 0.38) mortality were similar. CONCLUSIONS: BCIS was a frequent finding in FNF patients treated with hybrid THA. We found a paradoxically significant increase in BCIS with the use of UFH. Heparin did not seem to prevent BCIS, other thromboembolic events and mortality in this group of patients.

Three years of COVID-19 in children that attend the Mexican Social Security Institute's 1,350 child day-care centers, 2020-2023.

Background: Studies have suggested that children are less likely than adults to develop COVID-19; however, with the emergence of SARS-CoV-2 variants, hospitalization and death due to this cause have increased among the youngest ones. Methods: Retrospective, descriptive analytical study of the COVID-19 cases, hospitalizations and deaths occurred in children under five years who attended in Child Day-Care Centers (Centros de Atención Infantil-CAIs) of the Mexican Social Security Institute (IMSS) from 20th July 2020 to 31st March 2023. Results were compared with Mexico's and the US's national-level data. Incidence, attack (children and workers) and mortality rates were estimated. The risks of getting sick, being hospitalized and dying due to COVID-19 were calculated by year. Results: There were 4,369 COVID-19 cases among children from IMSS CAIs; 67 (1.5%) required hospitalization and only two deaths were reported (0.04%). Both at IMSS CAIs and at a national level in Mexico and the US, the highest incidences of COVID-19 among children under five years occurred during Omicron prevalence. The attack rate among workers (32.93%) was higher than children (4.99%). Hospitalization and mortality rates in the US decreased since the anti-COVID 19 vaccine was introduced in children older than six months, unlike the rates in Mexico, where the vaccine for this age group was not available. By the year 2020, the children that attended the IMSS CAIs were 77.3% less likely to be hospitalized; 80.9% in 2021, 93.2% in 2022, and 77.7% by March 2023, compared to same age children in Mexico. In 2021, the children that attended IMSS CAIs were 90.6% less likely to die due to COVID-19, and by March 2023, this likelihood was 34.3% lower than the rest of children in this age group in Mexico. Conclusions: Children that attended IMSS CAIs had a smaller risk of hospitalization and death due to COVID-19. However, the high rates of hospitalization and death due to SARS-CoV-2 in children under five years in our country point to the need and urgency of vaccination against this virus in this age group, as well as of the adherence to strict detection and medical referral protocols.

Single-Fluorophore Indicator to Explore Cellular and Sub-cellular Lactate Dynamics.

Lactate is an energy substrate and an intercellular signal, which can be monitored in intact cells with the genetically encoded FRET indicator Laconic. However, the structural complexity, need for sophisticated equipment, and relatively small fluorescent change limit the use of FRET indicators for subcellular targeting and development of high-throughput screening methodologies. Using the bacterial periplasmic binding protein TTHA0766 from Thermus thermophilus, we have now developed a single-fluorophore indicator for lactate, CanlonicSF. This indicator exhibits a maximal fluorescence change of 200% and a KD of ∼300 µM. The fluorescence is not affected by other monocarboxylates. The lactate indicator was not significantly affected by Ca2+ at the physiological concentrations prevailing in the cytosol, endoplasmic reticulum, and extracellular space, but was affected by Ca2+ in the low micromolar range. Targeting the indicator to the endoplasmic reticulum revealed for the first time sub-cellular lactate dynamics. Its improved lactate-induced fluorescence response permitted the development of a multiwell plate assay to screen for inhibitors of the monocarboxylate transporters MCTs, a pharmaceutical target for cancer and inflammation. The functionality of the indicator in living tissue was demonstrated in the brain of Drosophila melanogaster larvae. CanlonicSF is well suited to explore lactate dynamics with sub-cellular resolution in intact systems.

Medicines withdrawn in other countries due to safety concerns: should they continue to be available in the Argentine pharmaceutical market? / [Medicamentos retirados en otros países por problemas de seguridad: ¿Deben seguir presentes en el mercado farmacéutico argentino?]

Introduction: Numerous medicines have been withdrawn from the market because of the risks of serious adverse effects. The objective of this study was to identify in the Argentine pharmaceutical market (APM) the presence of medicines withdrawn in other countries due to safety problems, to analyze the information on their risks and to propose recommendations. Method: observational, descriptive study that explored the presence in the APM, until May 2021, of 462 medicines withdrawn in other countries. Those medicines on this list that are present in the APM and that are not currently authorized in countries with high sanitary surveillance were studied. Results: 17 medicines are still present in the APM, one over-the-counter. The package insert for 11 of the 17 medicines does not mention the adverse effects that led to their withdrawal. It was considered that the permanence in the APM of 16 of them should be reassessed. Conclusions: recommendations are made on actions to be taken by the regulatory authorities with the 17 medicines already present in the APM.

Introducción: Numerosos fármacos han sido retirados del mercado por sus riesgos de efectos adversos graves. El objetivo de este trabajo fue identificar en el mercado farmacéutico argentino (MFA) la presencia de medicamentos retirados en otros países por problemas de seguridad, analizar información sobre sus riesgos y proponer recomendaciones. Método: estudio observacional, descriptivo que exploró la presencia en el MFA, hasta mayo de 2021, de 462 medicamentos retirados en otros países. Se estudiaron aquellos medicamentos de esta lista presentes en el MFA y que no estuvieran autorizados actualmente en países de alta vigilancia sanitaria. Resultados: 17 medicamentos siguen presentes en el MFA, uno de venta libre.  El prospecto de 11 de los 17 fármacos no menciona los efectos adversos que motivaron su retiro. Se consideró que la permanencia en el MFA de 16 de ellos debería ser reevaluada. Conclusiones: se realizan recomendaciones sobre acciones a tomar por las autoridades reguladoras con los 17 medicamentos aún presentes en el MFA.

Exclusive circulation of canine parvovirus type 2c in the Guadalajara metropolitan area in western Mexico: a five-year study.

Canine parvovirus type 2 (CPV-2) infection in dogs is associated with severe gastroenteritis, bloody diarrhea, and vomiting, resulting in high rates of death, especially in unvaccinated puppies within the first months of age. There are three variants, called CPV-2a, CPV-2b, and CPV-2c, co-circulating worldwide. Our group previously reported that the only circulating CPV-2 variant in the Guadalajara metropolitan area in western Mexico was type 2c. Now, a five-year study was performed in order to investigate the possible dominance of CPV-2c in our region. Rectal swabs were collected from 146 dogs with clinical gastroenteritis from May 2014 to August 2019 at the Veterinary Hospital of the University of Guadalajara. Of these, 90 dogs tested positive for canine parvovirus by PCR. Most of the infected dogs with CPV-2 had a partial or incomplete vaccination status (n = 88, 97.8%). Approximately 65% (n = 59) of them were mixed-breed dogs, 77.8% (n = 70) were under 6 months of age, and 37.8% (n = 34) of them died from clinical complications. RFLP analysis of amplicons derived from the vp2 gene showed that all 90 DNA samples corresponded to CPV-2c, with no evidence of the presence of CPV-2a or CPV-2b variants. Twenty-nine of the 90 DNA samples were selected for amplification of a portion of the vp2 gene, and sequencing of these amplicons showed that all of them had the sequence GAA at codon 426, encoding the amino acid glutamic acid, which is characteristic of CPV-2c. Phylogenetic analysis showed that the CPV-2c sequences were related to those of viruses from Europe and South America. The present study indicates that CPV-2c is still the only variant circulating in the dog population of the Guadalajara metropolitan area.

Vaccine Effectiveness of CanSino (Adv5-nCoV) Coronavirus Disease 2019 (COVID-19) Vaccine Among Childcare Workers-Mexico, March-December 2021.

BACKGROUND: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) coronavirus disease 2019 (COVID-19) vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). METHODS: We evaluated CanSino VE within a childcare worker cohort that included 1408 childcare facilities. Participants were followed during March-December 2021 and tested through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% × (1 - hazard ratio for SARS-CoV-2 infection in fully vaccinated vs unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. RESULTS: The cohort included 43 925 persons who were mostly (96%) female with a median age of 32 years; 37 646 (86%) were vaccinated with CanSino. During March-December 2021, 2250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% confidence interval [CI], 10%-29%) against illness, 76% (95% CI, 42%-90%) against hospitalization, and 94% (95% CI, 66%-99%) against death. VE against illness declined from 48% (95% CI, 33%-61%) after 14-60 days following full vaccination to 20% (95% CI, 9%-31%) after 61-120 days. CONCLUSIONS: CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes.

[Septic hip arthritis after a closed acetabulum fracture treated conservatively. Case report]. / Artritis séptica de cadera luego de una fractura cerrada de acetábulo tratada en forma conservadora. Reporte de caso.

Necrotizing fasciitis is a life-threatening infection. Inmediate diagnosis and treatment are essential. Acetabulum fractures are a frequent identity in older adults today, associated with low-energy trauma. The indication for surgical or conservative treatment depends on multiple factors such as the age and comorbidities of the patient, the type and location of the fracture, and the socio-economic environment. We described an unusual case of infected hematoma, secondary to a closed acetabulum fracture, which led to septic arthritis of the hip joint.

Las fracturas de acetábulo asociadas a traumatismos de baja energía, son una identidad frecuente hoy en día en los adultos mayores. La indicación del tratamiento quirúrgico o conservador, depende de múltiples factores como la edad y las comorbilidades del paciente, el tipo y localización de la fractura, y el medio socio-económico. Independientemente del tratamiento elegido, ninguno está exento de complicaciones. Se describe a continuación un paciente con una fractura de acetábulo cerrada, de tratamiento conservador, que derivó en artritis séptica de la articulación coxofemoral.

[Results of surveys to users of IMSS children daycare centers during the COVID-19 pandemic]. / Resultados de encuestas a usuarios de guarderías IMSS durante la pandemia por COVID-19.

Background: Studies carried out in Mexico show that the COVID-19 pandemic has negatively impacted families in every field. Confinement has generated problems and economic, social and health instability in a large sector of the population, especially in the most vulnerable, to which children and adolescents are part of. Objective: To identify the impact of the confinement and closure of children daycare centers from the Instituto Mexicano del Seguro Social (IMSS) derived from the COVID-19 pandemic. Material and methods: Three questionnaire-type surveys were implemented via email for workers who were users of IMSS children daycare centers from September to November 2020. The surveys had a perception design, one- and two-stage, simple random and with results by segments. Results were obtained for independent proportions. The z-test was applied at 95% confidence. Results: Effects on workers and child users of the service derived from the closure of children daycare centers were observed, and it was greater in entities with closed children daycare centers than with those ones in operation (p < 0.0001). Conclusions: The negative impact derived from the closure of children daycare centers due to the confinement by COVID-19 in workers who use the service and their children was identified. The spheres with the greatest impact were the economic, the working environment, as well as the children's health (and their families).

Introducción: : estudios realizados en México muestran que la pandemia por COVID-19 ha impactado de forma negativa a las familias en todos los ámbitos. El confinamiento ha generado problemas e inestabilidad económica, social y en la salud en un gran sector de la población, especialmente en el más vulnerable, donde se encuentran los niños y adolescentes. Objetivo: identificar el impacto del confinamiento y el cierre de guarderías del Instituto Mexicano del Seguro Social (IMSS) derivado de la pandemia por COVID-19. Material y métodos: se aplicaron vía correo electrónico tres encuestas tipo cuestionario a trabajadores usuarios del servicio de guardería del IMSS de septiembre a noviembre de 2020. Las encuestas tenían diseño de percepción uni y bietápico, aleatorio simple y con resultados por segmentos. Se obtuvieron resultados para proporciones independientes. Se aplicó el z-test con un 95% de confianza. Resultados: se observó afectación en los trabajadores y en los niños usuarios del servicio derivado del cierre de las guarderías del IMSS, la cual fue mayor en las entidades con guarderías cerradas que en aquellas en operación (p < 0.0001). Conclusiones: se identificó el impacto negativo derivado del cierre de guarderías IMSS por el confinamiento por COVID-19 en trabajadores usuarios del servicio y sus hijos. Los ámbitos con más afectación fueron el económico, el laboral, así como la salud de los niños (y sus familias).

First Records of the Invading Species Drosophila Nasuta (Diptera: Drosophilidae) in the Amazon.

Invading species pose a growing threat to biodiversity, ecosystemic systems, regional economies, and public health. In recent decades, South America has received five exotic drosophilids species, some of which have invaded natural ecosystems and caused harm to agriculture. The most recent case is the Asian fly Drosophila nasuta Lamb. In the present study, we record D. nasuta in the Amazon, which is the largest and most biodiverse tropical rainforest in the world. Sampling of drosophilids was carried out between 2012 and 2017 in the Brazilian state of Pará. Drosophila nasuta was first detected on 1st July 2017, with 145 individuals of this species sampled among the 11,496 drosophilids caught. Although at low abundance, D. nasuta was recorded in forest fragments, anthropized fields, and urban environment. The records of the species occurred in the six municipalities of the state of Pará investigated at locations separated by approximately 700 km. In less than 10 years, D. nasuta has occupied approximately 2.5 million km2 in South America. The present findings assist in understanding the susceptibility of tropical forests to biological invasions.

Análisis epidemiológico multicéntrico de las fracturas de cadera en Uruguay: importancia y planificación de un registro nacional / Multicenter epidemiological analysis of hip fractures in Uruguay: importance and planning of a national register / Análise epidemiológica multicêntrica de fraturas de quadril no Uruguai: importância e planejamento de um registro nacional

Introducción: La incidencia de fracturas de cadera presenta un aumento dramático desde la mediana edad, constituyendo un problema de salud prevalente en adultos mayores. Se realizó una revisión bibliográfica de los registros internacionales de fracturas de cadera y un estudio epidemiológico multicéntrico para conocer la incidencia, los costos y la mortalidad de esta patología en nuestro país. Material y métodos: Se realizó una búsqueda, revisión y análisis de todos los registros internacionales de fracturas de cadera existentes en el mundo. Posteriormente, se llevó a cabo un análisis descriptivo observacional retrospectivo y multicéntrico en 4 instituciones de pacientes mayores de 50 años intervenidos quirúrgicamente con osteosíntesis por fractura de cadera en el año 2019. En los datos anonimizados se evaluaron edad, sexo, tipo de fractura, incidencia y costos. Se incluyeron y asociaron, además, datos estadísticos y económicos del Registro del Fondo Nacional de Recursos. Se utilizó el software estadístico SPSS para establecer asociaciones univariadas, bivariadas y multivariadas. Para comparar las proporciones se empleó el test estadístico de chi cuadrado. Resultados: Se resume la revisión de registros en una tabla. El análisis multicéntrico contó con 646 pacientes con fracturas de cadera. Destacamos la alta prevalencia de esta patología en pacientes mayores de 79 años (63,1%) y en el sexo femenino (77,6%), en concordancia con los registros internacionales, con asociación significativa entre ambas variables (p < 0,0001). A diferencia de otros registros, y quizás dato erróneo, la fractura más frecuente fue la del cuello de fémur (43%). El tiempo entre la fractura y la cirugía y los días de internación fueron de 2,6 y 7,2 días, respectivamente, en la institución de asistencia más efectiva. Nuestro cálculo mostró una incidencia de fractura de cadera en Uruguay que oscila entre 235 y 391 en 100.000 habitantes mayores de 50 años. El costo calculado de la serie evaluada fue de unos U$S 2.855.320 y, en general, esta patología provoca un gasto para nuestro país que se aproxima a U$S 20.000.000 por año. Conclusión: La fractura de cadera presenta una elevada incidencia, costos y morbimortalidad en la población de adultos mayores, comparable con datos internacionales. Es necesario contar con un Registro Nacional de Fracturas de Cadera que permita conocer datos estadísticos certeros para poder establecer políticas adecuadas de prevención, tratamiento y control de gastos.

Introduction: The incidence of hip fractures dramatically increases from middle age on, posing a prevalent health problem in elderly people. A literature review of the international hip fracture registers, as well as a multicenter, epidemiological study were carried out in order to assess the incidence, costs, and mortality of this pathology in our country. Material and methods: All international hip fracture registers in the world were searched, reviewed and analyzed. An observational, retrospective, multicenter descriptive analysis was then carried out in 4 health-care centers for patents over 50 years of age who underwent surgery with osteosynthesis due to hip fracture in 2019. Age, sex, type of fracture, incidence and costs were assessed from the anonymized data. Statistical and economic data from the National Resources Fund Register were also included and associated. The SPSS statistical software was used to establish univariate, bivariate, and multivariate associations. The chi-squared statistical test was used to compare proportions. Results: Review of the registers is summarized in a table. The multicenter analysis included 646 patients with hip fractures. Worth of note is the high prevalence of this pathology in patients over 79 years of age (63.1%) and females (77.6%), in line with the international registers, and a significant association between both variables (p < 0.0001). Unlike other registers, and probably due to inaccurate data, the most frequent fracture was that of femoral neck (43%). The time from fracture to surgery and inpatient days were 2.6 and 7.2 days, respectively, in the most effective health care center. Our calculation showed a hip fracture incidence in Uruguay between 235 and 391 per 100,000 inhabitants over 50 years of age. The estimated cost of the assessed series was about U$S 2,855,320, and in general this pathology generates an annual expense of about U$S 20,000,000 for our country. Conclusion: Hip fractures have high incidence, costs and mortality and morbidity in the elderly population comparable with international data. It is necessary to have a National Hip Fracture Register that provides accurate statistical data in order to establish adequate prevention, treatment and cost control policies.

Introdução: A incidência de fraturas de quadril apresenta um aumento dramático a partir da meia-idade, constituindo um problema de saúde prevalente em idosos. Uma revisão bibliográfica dos Registros Internacionais de Fratura de Quadril e um estudo epidemiológico multicêntrico foram realizados para determinar a incidência, os custos e a mortalidade dessa patologia em nosso país. Material e métodos: Foi realizada uma busca, revisão e análise de todos os Registros Internacionais de fraturas de quadril existentes no mundo. Posteriormente, foi realizada uma análise observacional descritiva retrospectiva e multicêntrica, em 4 Instituições, de pacientes maiores de 50 anos, submetidos à cirurgia com osteossíntese, para fratura de quadril em 2019. Nos dados anônimos foram avaliados idade e sexo, tipo de fratura , incidência e custos. Dados estatísticos e econômicos do Registro do Fundo Nacional de Recursos também foram incluídos e associados. O software estatístico SPSS foi usado para estabelecer associações univariadas, bivariadas e multivariadas. O teste estatístico do qui quadrado foi usado para comparar as proporções. Resultados: a revisão dos registros é resumida em uma tabela. A análise multicêntrica incluiu 646 pacientes com fraturas de quadril. Destaca-se a alta prevalência dessa patologia em pacientes maiores de 79 anos (63,1%) e no sexo feminino (77,6%), de acordo com registros internacionais, com associação significativa entre as duas variáveis ​​(p <0,0001). Ao contrário de outros registros, e talvez dados errôneos, a fratura mais frequente foi a do colo do fêmur (43%). O tempo decorrido entre a fratura e a cirurgia e os dias de internação foram de 2,6 e 7,2 dias, respectivamente, na instituição assistencial mais efetiva. Nosso cálculo mostrou uma incidência de fratura de quadril no Uruguai, variando entre 235 e 391 em 100.000 habitantes com mais de 50 anos de idade. O custo calculado da série avaliada foi em torno de US $ 2.855.320 e, em geral, essa patologia acarreta um gasto para o nosso país que é próximo a US $ 20.000.000 por ano. Conclusão: A fratura de quadril tem alta incidência, custo e morbimortalidade na população idosa, comparável a dados internacionais. É necessário um Cadastro Nacional de Fraturas de Quadril, que permita conhecer dados estatísticos precisos, para estabelecer políticas adequadas de prevenção, tratamento e controle de custos.