Assessing refrigerated preservation performance using Listeria predictive microbiology models and temperature data: Refrigerator performance indicator and time-temperature equivalent.

Time-temperature data for queso fresco (QF) cheese varieties stored in a residential refrigerator operating at 5°C and a predictive microbiology secondary model for Listeria monocytogenes in QF were used to estimate a refrigerator performance indicator (RPI) of microbial preservation. RPI values were used to assess how compressor technology (single [SS] and variable speed [VS]), ambient temperature (21.1°C [LT] and 32.2°C [HT]), and refrigerator load (22.5 kg regular load and 39 kg higher load) affected preservation performance. All deterministic and probabilistic RPI estimations slightly exceeded the desirable 1.0 value, i.e., the variable temperatures for the QF kept in the refrigerator were worse than keeping it constantly at the temperature recommended by food safety agencies for QF. Furthermore, the mean comparison of estimates of the time-temperature equivalent indicator previously developed by French researchers showed similar behavior to those observed for RPI. Finally, statistical analysis showed that Tambient was the factor with the highest impact on refrigerator performance because of its impact on the sample temperature increase during door openings and when exposed to ambient temperature during product use. This highlights the need to reduce the time for product temperature recovery by improving the compressor operation logic. Also important are consumer behavior changes such as a reduction in product exposure to ambient temperature and in the door opening duration and frequency. PRACTICAL APPLICATION: This study demonstrated how a quantitative tool (RPI) can assess refrigerator preservation performance. Although the findings presented can be applied to any cold chain segment, the data used was collected for its weakest link, the domestic refrigerator. Surveys show that 77% of them operate above the recommended 4°C. The RPI methodology is ready for use by refrigerator designers to assess performance improvements possible by modifications of the compressor operation logic. Moreover, it can be integrated into smart-hubs monitoring the frequency and duration of refrigerator door openings to inform consumers when their habits are compromising the preservation performance of the refrigerator.

Incidence of obstetric anal sphincter injuries according to the type of forceps used in the Mexican population.

OBJECTIVE: This study describes the frequency of obstetric anal sphincter injuries (OASIS) in patients after instrumental delivery according to the type of forceps used. METHODS: A retrospective comparative cohort study was conducted on patients who underwent instrumental delivery from January 2017 to April 2022. The primary outcome was the presence of OASIS following delivery. Patients were categorized into Cohort A if only rotation forceps were used, Cohort B for only traction forceps, and Cohort C if both types were used sequentially. Statistical analysis was performed with SPSS (IBM, New York, NY) with χ2, Fisher's exact, and analysis of variance testing. A P-value <0.05 was considered significant. RESULTS: OASIS occurred in 45 of 328 instrumental deliveries. OASIS after rotation forceps occurred in 12.9% (n = 8) of cases, after traction forceps in 13.2% (n = 34), and after sequential use of rotation and traction forceps in 37.5% (n = 3) of cases (p = 0.141). An odds ratio (OR) of 0.91 (95% confidence interval [CI] 0.40-2.08) for OASIS was obtained with the use of rotation forceps, 0.81 (95% CI 0.38-1.70) for traction forceps, and 3.97 (95% CI 0.91-17.2) for the sequential use of rotation and traction forceps. CONCLUSION: There were no significant differences in the presence of OASIS comparing traction and rotation forceps. A non-significant trend of higher OASIS following the sequential use of traction and rotation forceps was observed.

Alpha-Synuclein Gene Alterations Modulate Tyrosine Hydroxylase in Human iPSC-Derived Neurons in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) caused by SNCA gene triplication (3XSNCA) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3XSNCA and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3XSNCA, a gene-edited isogenic line with a frame-shift mutation on all SNCA alleles (SNCA 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the SNCA 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3XSNCA and SNCA 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, SNCA gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight SNCA's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.

Hepatitis C virus NS5A and core protein induce fibrosis-related genes regulation on Huh7 cells through activation of LX2 cells.

INTRODUCTION AND OBJECTIVES: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. MATERIALS AND METHODS: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. RESULTS: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFß1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. CONCLUSIONS: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection.

Uncovering a novel mechanism: Butyrate induces estrogen receptor alpha activation independent of estrogen stimulation in MCF-7 breast cancer cells.

Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients' health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs.

Influência da exposição ambiental na percepção do estado de saúde de indivíduos de cinco países latino-americanos / Effect of environmental exposure on the perceived health status of individuals from five Latin American countries

OBJETIVO: A relação entre exposição ambiental e risco à saúde é amplamente reconhecida e a avaliamos em cinco países da América Latina com condições culturais distintas, mas com Índices de Desenvolvimento Humano semelhantes. MÉTODOS: Estudo transversal envolvendo 3.016 indivíduos (18 a 75 anos) oriundos de: Argentina (n = 878), Brasil (n = 1.030), México (n = 272), Paraguai (n = 508) e Peru (n = 328). A seleção foi aleatória e todos responderam questionário padronizado (fatores sociodemográficos, fatores ambientais e hábitos de vida) derivado do Clinical Screening Tool for Air Pollution Risk. Segundo o estado atual de saúde, foram categorizados em: saúde regular/má/péssima ou excelente/boa. Tendo-a como desfecho, realizou-se análise multivariada.Os dados foram apresentados como razão de verossimilhança (RV) e intervalos de confiança de 95% (IC 95%), tendo-se 5% o nível de significância. RESULTADOS: Foram significantemente associados a pior percepção de situação de saúde: morar em qualquer um dos países, ter umidade na residência (OR = 1,68; IC 95%: 1,33-2,12), dirigir automóvel com janelas abertas (OR = 1,31; IC 95%: 1,03-1,65), ter baixa renda familiar (OR = 1,59; IC 95%: 1,26-2,01), nível educacional incompleto (OR = 1,54; IC 95%: 1,22-1,94), histórico pessoal/familiar de hipertensão arterial (OR = 2,25; IC 95%: 01,64-3,09), doença pulmonar obstrutiva crônica/asma (OR = 1,74; IC 95%: 1,28-2,36), diabete melito (OR = 3,74; IC 95%: 2,23-6,29), obesidade (OR = 1,84; IC 95%: 1,84-3,19) ou comorbidades oftalmológicas (OR = 1,89; IC 95%: 1,55-2,30); realizar exercícios ao ar livre (OR = 1,60; IC 95%: 1,31-1,96). CONCLUSÕES: Apesar das diferentes exposições a que foram submetidos, alguns fatores permanecem muito significativos, e ter baixa renda familiar, expor-se à poluição e ter antecedentes de doenças crônicas foram associados à percepção de condição ruim de saúde.

OBJECTIVE: The relationship between environmental exposure and health outcomes is well known.We investigated this relationship in five Latin American countries with different cultural backgrounds but similar Human Development Indexes. METHODS: This was a cross-sectional study involving 3,016 individuals (18 to 75 years old) from Argentina (n=878), Brazil (n=1030), Mexico (n=272), Paraguay (n=508), and Peru (n=328). Participants were randomly selected and responded to a standardized questionnaire (including sociodemographic and environmental factors and lifestyle habits) derived from a clinical screening tool for air pollution risk. Based on their current health status, participants were categorized as having regular/bad/very bad or excellent/good health. Multivariate analysis was conducted, and data were presented as likelihood ratios and 95% confidence intervals (95%CI).The significance level was set at 5%. RESULTS: Living in any of the study countries; indoor humidity (OR=1.68; 95%CI: 1.33-2.12); driving with the windows open (OR=1.31; 95%CI: 1.03-1.65); low family income (OR=1.59; 95%CI: 1.26-2.01); incomplete education (OR=1.54; 95%CI: 1.22-1.94); personal/family history of hypertension (OR=2.25; 95%CI: 01.643.09), chronic obstructive pulmonary disease/asthma (OR=1.74; 95%:CI: 1.28-2.36), diabetes (OR=3.74; 95%CI:2.23-6.29), obesity (OR=1.84; 95%CI: 1.84-3.19), or ocular comorbidities (OR=1.89; 95%CI: 1.55-2.30); and exercising outdoors (OR=1.60; 95%CI: 1.31-1.96) were significantly associated with a worse perceived health status. CONCLUSIONS: Despite the different exposures to which participants were subjected, some factors remain very significant. Low family income, exposure to pollution, and a history of chronic diseases were associated with the perception of a poor health condition.

Rational Design of Benzobisheterocycle Metallo-ß-Lactamase Inhibitors: A Tricyclic Scaffold Enhances Potency against Target Enzymes.

Antimicrobial resistance is a global public health threat. Metallo-ß-lactamases (MBLs) inactivate ß-lactam antibiotics, including carbapenems, are disseminating among Gram-negative bacteria, and lack clinically useful inhibitors. The evolving bisthiazolidine (BTZ) scaffold inhibits all three MBL subclasses (B1-B3). We report design, synthesis, and evaluation of BTZ analogues. Structure-activity relationships identified the BTZ thiol as essential, while carboxylate is replaceable, with its removal enhancing potency by facilitating hydrophobic interactions within the MBL active site. While the introduction of a flexible aromatic ring is neutral or detrimental for inhibition, a rigid (fused) ring generated nM benzobisheterocycle (BBH) inhibitors that potentiated carbapenems against MBL-producing strains. Crystallography of BBH:MBL complexes identified hydrophobic interactions as the basis of potency toward B1 MBLs. These data underscore BTZs as versatile, potent broad-spectrum MBL inhibitors (with activity extending to enzymes refractory to other inhibitors) and provide a rational approach to further improve the tricyclic BBH scaffold.

Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson's Disease.

In Parkinson's disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson's model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.

Changes in the Proliferation of the Neural Progenitor Cells of Adult Mice Chronically Infected with Toxoplasma gondii.

During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ® software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.

Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.

Efectividad de refuerzos homólogos y heterólogos luego de esquemas primarios con Sputnik V, Astra-Zeneca y Sinopharm durante el período omicron en adultos mayores de 50 años en la provincia de Buenos Aires / Effectiveness of homologous and heterologous boosters after primary regimens with Sputnik V, AstraZeneca, and Sinopharm during the omicron variant period in adults over 50 years old in the province of Buenos Aires

Objetivo: Evaluar la efectividad de esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o combinaciones heterólogas seguidos de refuerzos a vector viral (Sputnik V, Astra-Zeneca) o ARNm (Pfizer-BioNTech, Moderna) frente a infecciones, hospitalizaciones y muertes por SARS-CoV-2. Material y métodos: Estudio de casos y controles con test negativo realizado en la provincia de Buenos Aires, durante el predominio de ómicron BA.1, que incluyó individuos ≥ 50 años con test positivo para SARS-CoV-2 que habían recibido 2 o 3 dosis de vacunas. Se registraron infecciones, hospitalizaciones y muertes después de administrar refuerzos con Sputnik V, Astra-Zeneca o ARNm. Resultados: De 422 124 personas analizadas para SARS-Cov-2, 221 993 (52.5%) presentaron test positivos; 190 884 (45.2%) y 231.260 (54.8%) recibieron esquemas de vacunación de 2 y 3 dosis, respectivamente. Los esquemas primarios con Astra-Zeneca, Sputnik V o vector viral, combinados con un refuerzo a vector viral, mostraron protección contra infecciones (OR: 0.94 [0.92 a 0.97]), hospitalizaciones (OR: 0.30 [0.26 a 0.35]) y muertes (OR: 0.29 [0.25 a 0.33]. Los esquemas primarios con Astra-Zeneca y Sputnik V más refuerzo de ARNm, o con Sinopharm más refuerzo de ARNm o vector viral otorgaron protección adicional contra infecciones (OR: 0.70 [0.68 a 0.71]). Hubo un efecto protector frente a hospitalizaciones y muertes (OR: 0.26 [0.22 a 0.31] y 0.22 [0.18 a 0.25]) en todos los casos. Conclusiones: Durante el predominio de ómicron, los refuerzos heterólogos con vacunas a vector viral y de ARNm, posteriores a los esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o heterólogos, podrían proporcionar mejor protección y mayor duración del efecto contra la muerte en personas mayores de 50 años, en comparación con refuerzos homólogos

Objective: To evaluate the effectiveness of primary vaccination regimens involving Sputnik V, Astra-Zeneca, Sinopharm, or heterologous combinations followed by viral vector boosters (Sputnik V, As-traZeneca) or mRNA boosters (Pfizer-BioNTech, Moderna) against infections, hospitalizations and deaths caused by SARS-CoV-2. Material and methods: Case-control studies with negative tests conducted in the Buenos Aires province during the Omicron BA.1 predominance. The study included patients ≥ 50 years of age, who tested positive for SARS-CoV-2 and had received two or three doses of vaccines. Infections, hospitalizations, and deaths were registered following the administration of Sputnik V, AstraZeneca, or mRNA boosters. Findings: Out of 422 124 people tested for SARS-Cov-2, 221 993 (52.5%) had positive test results; 190,884 (45.2%) and 231 260 (54.8%) received two-dose and three-dose vaccination schemes, respectively. Primary regimens with AstraZeneca, Sputnik V, or viral vector, combined with a viral vector booster demonstrated protection against infections (OR 0.94 [0.92 to 0.97]), hospitalizations (OR 0.30 [0.26 to 0.35]) and deaths (OR 0.29 [0.25 to 0.33]. Primary regimens with AstraZeneca and Sputnik V combined with mRNA boosters, as well as pri-mary schemes with Sinopharm combined with mRNA or viral vectored boosters showed additional protection against infections (OR 0.70 [0.68 to 0.71]). There was a protective effect against hospi-talizations and deaths (OR 0.26 [0.22-0.31] and 0.22 [0.18 -0.25]) in all cases. Conclusions: During Omicron predominance, heterologous boosters with viral-vector and mRNA vaccines, administered after Sputnik V, AstraZeneca, Sinopharm, or heterologous primary regimens, could provide enhanced protection and prolonged effectiveness against mortality in individuals aged ≥ 50, compared to ho-mologous boosters

Safety and immunogenicity of a SARS-CoV-2 Gamma variant RBD-based protein adjuvanted vaccine used as booster in healthy adults.

A Gamma Variant RBD-based aluminum hydroxide adjuvanted vaccine called ARVAC CG was selected for a first in human clinical trial. Healthy male and female participants (18-55 years old) with a complete COVID-19-primary vaccine scheme were assigned to receive two intramuscular doses of either a low-dose or a high-dose of ARVAC CG. The primary endpoint was safety. The secondary objective was humoral immunogenicity. Cellular immune responses were studied as an exploratory objective. The trial was prospectively registered in PRIISA.BA (Registration Code 6564) and ANMAT and retrospectively registered in ClinicalTrials.gov (NCT05656508). Samples from participants of a surveillance strategy implemented by the Ministry of Health of the Province of Buenos Aires that were boosted with BNT162b2 were also analyzed to compare with the booster effect of ARVAC CG. ARVAC CG exhibits a satisfactory safety profile, a robust and broad booster response of neutralizing antibodies against the Ancestral strain of SARS-CoV-2 and the Gamma, Delta, Omicron BA.1 and Omicron BA.5 variants of concern and a booster effect on T cell immunity in individuals previously immunized with different COVID-19 vaccine platforms.

Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires / Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study

Resumen Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes >18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró adminis tración temprana o tardía a la infusión de TCZ ≤ ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no inva siva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Abstract Introduction: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. Methods: Multicenter, retrospective cohort study in cluding patients>18 years hospitalized between 7/1/2021- 8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. Results: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Com pared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). Discussion: This study supports the early use of TCZ in patients with severe or critical COVID-19.

[Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study]. / Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires.

INTRODUCTION: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. METHODS: Multicenter, retrospective cohort study including patients >18 years hospitalized between 7/1/2021-8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were 28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. RESULTS: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Compared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). DISCUSSION: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes > 18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró administración temprana o tardía a la infusión de TCZ = ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no invasiva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

A comprehensive case study on the sustainability of tropical dairy cattle farming in Oaxaca, Mexico / Um estudo de caso abrangente sobre a sustentabilidade da pecuária leiteira tropical em Oaxaca, México

Tropical dairy cattle farming is one the most relevant economic activities for food production; although, currently faces increasing scrutiny from society due to its potential harm to natural resources and the environment. Moreover, some factors are paramount for the evaluation of the sustainability and productive potential of any given tropical dairy farm: soil quality, profitability, and energy efficiency. This study carried out a sustainability analysis in four types of tropical dairy cattle ranches, through three key indicators (economic profitability, energy efficiency and soil quality) and with a comprehensive approach in the Costa region of Oaxaca, Mexico. Therefore, four farms of different sizes (i.e., small, medium, large, and very large) were selected in Costa de Oaxaca, Mexico. The data collection was carried out for daily milk production, the dynamics of farm inputs (introduction or removal) from the production system, alongside with collection of soil samples. The agroecosystems evaluated were economically profitable, and those with greater intensification of their pasture areas display higher profit margins and energy efficiency. In terms of soil quality, there is a regular potential for its rational utilization.

A pecuária leiteira tropical é uma das atividades econômicas mais relevantes para a produção de alimentos, embora atualmente enfrente crescente discussão da sociedade devido ao seu potencial dano aos recursos naturais e ao meio ambiente. Além disso, alguns fatores são primordiais para a avaliação da sustentabilidade e potencial produtivo de qualquer popriedade leiteira tropical: qualidade do solo, rentabilidade e eficiência energética. O objetivo deste estudo foi realizar uma análise de sustentabilidade em quatro tipos de propriedades de gado leiteiro tropical, por meio de três indicadores chave (rentabilidade econômica, eficiência energética e qualidade do solo) e com uma abordagem abrangente na região da Costa de Oaxaca, México. Portanto, quarto propriedades de diferentes tamanhos (isto é, pequenas, médias, grandes e muito grandes) foram selecionadas na Costa de Oaxaca, México. A coleta de dados foi realizada para a produção diária de leite, a dinâmica dos insumos da fazenda (introdução ou retirada) do sistema de produção, juntamente com coleta de amostras de solo. Os agroecossistemas avaliados foram economicamente rentáveis, sendo que aqueles com maior intensificação de suas áreas de pastagens apresentam maiores margens de lucro e eficiência energética. Em termos de qualidade do solo, existe um potencial regular para a sua utilização racional.

Resultados del taller para residentes de ginecoobstetricia en reparación de episiotomías y desgarros obstétricos / Results of workshop for obstetrics and gynecology residents on episiotomy and injury obstetric tear repair

Resumen OBJETIVO: Evaluar los conocimientos, satisfacción y nivel de confianza de los médicos residentes de Ginecología y Obstetricia luego de haber participado en un taller de simulación de reparación de episiotomías y desgarros perineales severos. MATERIALES Y MÉTODOS: Estudio observacional y transversal efectuado en residentes de la especialidad de Ginecología y Obstetricia en junio del 2022. Se aplicaron cuestionarios de conocimientos antes y después del taller, una encuesta de satisfacción y nivel de confianza, así como una lista de cotejo para valorar el desempeño en la ejecución de la técnica de reparación de episiotomías y desgarros. Se utilizó estadística descriptiva y prueba de t pareada para la comparación antes y después de las muestras relacionadas. Se consideró significancia estadística una p < 0.05. RESULTADOS: Se incluyeron 37 médicos residentes de todos los grados académicos. La media de la evaluación preprueba fue de 14.89 ± 0.54 puntos y 15.81 ± 0.41 puntos en la posprueba (p = 0.233). Durante la práctica de reparación de la episiotomía, 34 de los 37 residentes reconocieron estructuras anatómicas y todos seleccionaron adecuadamente el material de sutura. En el taller de desgarros perineales 25 de 37 reconocieron las estructuras anatómicas y todos, menos uno, seleccionaron adecuadamente el material. CONCLUSIONES: El taller con modelos animales de simulación tiene un alto grado de satisfacción y nivel de confianza; sin embargo, en este estudio no se observó mejoría en los conocimientos. Este efecto positivo en los médicos en vías de especialización permite identificar, de manera oportuna, las lesiones del esfínter anal, llevar a cabo una correcta reparación y, en consecuencia, disminuir la incidencia de disfunciones asociadas con el traumatismo obstétrico perineal.

Abstract OBJECTIVE: To assess the knowledge, satisfaction and level of confidence of Gynaecology and Obstetrics residents after participating in a simulation workshop on episiotomy and severe perineal tear repair. MATERIALS AND METHODS: Observational and cross-sectional study carried out in residents of the speciality of Gynaecology and Obstetrics in June 2022. Knowledge questionnaires were administered before and after the workshop, a satisfaction and confidence level survey, as well as a checklist to assess the post-workshop episiotomy and tear repair technique. Descriptive statistics and paired t-test were used for pre- and post-test comparison. A p < 0.05 was considered statistically significant. RESULTS: Thirty-seven resident physicians of all academic grades were included. The mean pre-test assessment was 14.89 ± 0.54 points and 15.81 ± 0.41 points at post-test, p = 0.233. During episiotomy repair practice, 34 of the 37 residents recognized anatomical structures and all selected suture material appropriately. In the perineal tears workshop 25 of 37 recognized anatomical structures and all but one selected material appropriately. CONCLUSIONS: The workshop with simulation animal models has a high satisfaction and confidence level; however, no improvement in knowledge was observed in this study. This positive effect on trainee doctors allows early identification of anal sphincter injuries, correct repair and consequently a decrease in the incidence of dysfunction associated with perineal obstetric trauma.

Tratamiento del síndrome de vejiga hiperactiva mediante estimulación transcutánea bilateral del nervio tibial posterior / Treatment of overactive bladder syndrome by bilateral transcutaneous posterior tibial nerve stimulation

Resumen OBJETIVO: Determinar si la estimulación transcutánea bilateral del nervio tibial posterior disminuye los síntomas de la vejiga hiperactiva y mejora la calidad de vida. MATERIALES Y MÉTODOS: Estudio de cohorte simple, retrospectivo, efectuado en pacientes atendidas en la clínica de Urología Ginecológica del Instituto Nacional de Perinatología Isidro Espinosa de los Reyes en la Ciudad de México, del 8 de octubre de 2021 al 14 de julio de 2022 a quienes se aplicó terapia de electroestimulación bilateral transcutánea del nervio tibial posterior para tratar el síndrome de vejiga hiperactiva.Parámetros de estudio: severidad, calidad de vida y diario miccional en las sesiones 1, 6 y 12. Para la comparación al inicio y al final del tratamiento se utilizó estadística descriptiva y prueba de t pareada; la p < 0.05 se consideró estadísticamente significativa. RESULTADOS: Se estudiaron 25 pacientes: 23 con disminución del puntaje en el cuestionario de calidad de vida King's Health de 24.5 entre las sesiones 1 y 12 (p < 0.001). La disminución del puntaje de severidad de síntomas (Overactive Bladder Symptom Severity [OABSS]) fue de 16.6 entre las sesiones 1 y 12 (p < 0.001). Se observó mejoría significativa en todos los parámetros del diario miccional. CONCLUSIÓN: En esta muestra, la estimulación transcutánea bilateral del nervio tibial posterior disminuyó de manera importante los síntomas de vejiga hiperactiva y mejoró la calidad de vida.

Abstract OBJECTIVE: To determine whether bilateral transcutaneous stimulation of the posterior tibial nerve reduces symptoms of overactive bladder and improves quality of life. MATERIALS AND METHODS: Simple, retrospective, cohort study carried out in patients attended at the gynaecological urology clinic of the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes in Mexico City, from 8 October 2021 to 14 July 2022 to whom bilateral transcutaneous electrostimulation therapy of the posterior tibial nerve was applied to treat overactive bladder syndrome. Study parameters: severity, quality of life and voiding diary in sessions 1, 6 and 12. Descriptive statistics and paired t-test were used for comparison at baseline and at the end of treatment; p < 0.05 was considered statistically significant. RESULTS: Twenty-five patients were studied: 23 with a decrease in King's Health quality of life score of 24.5 between sessions 1 and 12 (p < 0.001). The decrease in symptom severity score (OABSS) was 16.6 between sessions 1 and 12 (p < 0.001). Significant improvement was observed in all voiding diary parameters. CONCLUSION: In this sample, bilateral transcutaneous posterior tibial nerve stimulation significantly decreased overactive bladder symptoms and improved quality of life.

Distribución de las garrapatas exófilas en las principales ecorregiones de Guatemala / Distribution of exophilic ticks in the main ecoregions of Guatemala

Las garrapatas son ectoparásitos hematófagos obligados que actúan como vectores biológicos de diversos patógenos ya que parasitan aves, reptiles y mamíferos. Las enfermedades en las cuales actúan como vectores son la anaplasmosis, piroplasmosis, borreliosis, theileriosis y diversas enfermedades rickettsiales. La presencia de garrapatas es mediada por factores ambientales, geográficos y microclimáticos incluso es influenciada por la abundancia de hospedadores, además de ser estos considerados indicadores filogenéticos, ecológicos y biogeográficos de las especies que parasitan. El objetivo del estudio fue conocer la diversidad de especies de garrapatas exófilas en las principales ecorregiones de Guatemala, con la finalidad de determinar la abundancia y su distribución, así como su potencial vectorial ante agentes patógenos de interés veterinario y zoonótico. Se muestrearon cuatro áreas protegidas que representan las ecorregiones más extensas de Guatemala. Se realizaron tres repeticiones en cada sitio de muestreo utilizando la técnica del bandereo. Las garrapatas colectadas fueron colocadas en frascos con etanol al 90% para su preservación y posterior análisis microscópico. Se observaron las garrapatas colectadas utilizando un estero microscopio y claves morfológicas para su identificación. Los datos fueron resumidos utilizando tablas de frecuencia y estadística descriptiva. Las especies encontradas fueron Ixodes affinis en estadío adulto y larvas del género Rhipicephalus sp. El promedio del índice de abundancia para garrapatas adultas fue de 1.68 y para larvas de 33.51. Las especies encontradas en el presente estudio se consideran vectores de interés en medicina veterinaria. Sin embargo, el género Rhipicephalus sp. puede parasitar al humano y transmitir enfermedades Rickettsiales.

Ticks are obligate hematophagous ectoparasites that act as biological vectors of various pathogens since they parasitize birds, reptiles and mammals. The diseases in which they act as vectors are anaplasmosis, piroplasmosis, borreliosis, theileriosis and various rickettsial diseases. The presence of ticks is mediated by environmental, geographic and microclimatic factors and is even influenced by the abundance of hosts, in addition to these being considered phylogenetic, ecological and biogeographic indicators of the species they parasitize. The objective of the study wasto know the diversity of exophilic tick speciesin the main ecoregions of Guatemala, with the purpose of determining their abundance and distribution, as well as their vector potential against pathogenic agents of veterinary and zoonotic interest. Four protected areas that represent the largest ecoregions of Guatemala were sampled. Three repetitions were carried out at each sampling site using the flagging technique. The collected ticks were placed in jars with 90% ethanol for preservation and subsequent microscopic analysis. The collected ticks were observed using a stereomicroscope and morphological keys for identification. Data were summarized using frequency tables and descriptive statistics. The species found were Ixodes affinis in the adult stage and larvae of the genus Rhificephalus sp. The average abundance index for adult ticks was 1.68 and for larvae was 33.51. The species found in the present study are considered vectors of interest in veterinary medicine. However, the genus Rhipicephalus sp. It can parasitize humans and transmit Rickettsial diseases.

[Combination of modifying therapies in type 2 spinal muscular atrophy]. / Combinación de terapias modificadoras en atrofia muscular espinal tipo 2.

Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disorder showing peripheral hypotonia, atrophy, and weakness in the extremities and bulbar muscles. It is caused by the homozygous deletion of the SMN1 gene on chromosome 5q13. Before 2016, there was no treatment to modify the disease, and in that year it was approved nusinersen, the first drug available to treat this disease, whose action mechanism consists in regulating the SMN2 gene to increase the survival motor neuron (SMN) levels. More recently, the gene therapy onasemnogene aberparvovec-xioi (OAX) was approved for patients under two years of age. The human SMN1 gene is delivered intravenously through an adeno-associated viral type 9 vector. Both therapies appear to show significant improvement in motor function without the presence of severe adverse effects. However, it is unclear whether both treatments can be used together. Clinical case: A 24-month-old male patient with a diagnosis of SMA at 18 months of age. First, he was treated with intrathecal nusinersen administration and later with OAX. When assessing the CHOP INTEND and HFSME function scales, the patient showed an increase in the performance of his motor functions. Conclusion: OAX and nusinersen could be considered in sequence therapies in the presence of SMA. However, this therapy is not yet well established and has not been studied in the long term.

Introducción: la atrofia muscular espinal (AME) es un trastorno neuromuscular autosómico recesivo que se presenta con hipotonía periférica, atrofia y debilidad en las extremidades y músculos bulbares. Es causada por la deleción en estado homocigoto del gen SMN1 en el cromosoma 5q13. Antes de 2016, no había tratamiento modificador de la enfermedad y en ese año fue aprobado el nusinersen, el primer medicamento disponible para esta enfermedad, cuyo mecanismo de acción es modular el gen SMN2 para producir mayor cantidad de proteína de supervivencia de la motoneurona (SMN). En 2019 se aprobó el onasemnogene abeparvovec-xioi (OAX), primer fármaco disponible que utiliza terapia génica. Este se puede emplear únicamente en pacientes menores de dos años y consiste en administrar vía intravenosa el gen humano SMN1 mediante un vector viral adenoasociado tipo 9, con lo que se inicia la producción de proteína SMN. Ambas terapias han demostrado mejoría significativa de la función motora y sin presencia de eventos adversos serios. Sin embargo, aún no está claramente establecido si ambas terapias pueden usarse en conjunto. Caso clínico: paciente de sexo masculino de 24 meses de edad con diagnóstico de AME a los 18 meses, el cual fue tratado inicialmente con nusinersen intratecal y posteriormente con OAX. Al evaluar las escalas de función CHOP INTEND y HFSME el paciente presentó un aumento en el desempeño de sus funciones motoras. Conclusión: el OAX y el nusinersen podrían considerarse terapias en secuencia ante la AME. Sin embargo, esta terapia aún no está bien establecida y no se ha estudiado a largo plazo.