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Introduction: Stress is a pervasive health concern known to induce physiological changes, particularly impacting the vulnerable hippocampus and the morphological integrity of its main residing cells, the hippocampal neurons. Eye Movement Desensitization and Reprocessing (EMDR), initially developed to alleviate emotional distress, has emerged as a potential therapeutic/preventive intervention for other stress-related disorders. This study aimed to investigate the impact of Acute Variable Stress (AVS) on hippocampal neurons and the potential protective effects of EMDR. Methods: Rats were exposed to diverse stressors for 7 days, followed by dendritic morphology assessment of hippocampal neurons using Golgi-Cox staining. Results: AVS resulted in significant dendritic atrophy, evidenced by reduced dendritic branches and length. In contrast, rats receiving EMDR treatment alongside stress exposure exhibited preserved dendritic morphology comparable to controls, suggesting EMDR's protective role against stressinduced dendritic remodeling. Conclusions: These findings highlight the potential of EMDR as a neuroprotective intervention in mitigating stress-related hippocampal alterations.

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Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.

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Las personas obesas enfrentan mayores complicaciones al contraer SARS-CoV-2 debido a su estado proinflamatorio crónico y respuesta inmune reducida, relacionados con el exceso de tejido adiposo. La interacción del virus con los receptores ACE2 y la retención de lípidos ectópicos renales son aspectos clave en este contexto. Objetivo. Analizar las características específicas de la obesidad que aumentan la susceptibilidad a síntomas graves de COVID-19, a partir de artículos publicados entre 2020 y 2022, y promover futuras investigaciones. Metodología. Se realizó una revisión sistemática de artículos originales entre 2020 y 2022 utilizando términos clave y operadores booleanos en bases de datos como PubMed, Scopus, ProQuest, etc. Se excluyeron estudios no originales para obtener investigaciones más específicas. Resultados. De 180 artículos encontrados, 42 fueron seleccionados. Entre estos, se destacó que pacientes obesos, especialmente hombres de edad avanzada, presentaron severas complicaciones. Sin embargo, jóvenes con obesidad severa y personas con bajo peso también mostraron mayor riesgo de mortalidad. La disminución de la función pulmonar, bajos niveles de vitamina D, y la alteración de ACE2 fueron implicados en la gravedad de la infección. La hiperglucemia asociada a la obesidad aumentó el riesgo de ingreso a UCI y ventilación mecánica, mientras que la resistencia a la insulina empeoró el pronóstico. Conclusión. La obesidad emerge como un factor de riesgo importante para la gravedad y mortalidad por COVID-19, señalando la necesidad de una atención específica para este grupo de pacientes y la continuación de investigaciones en el área.

Obese individuals face greater complications in contracting SARS-CoV-2 due to their chronic proinflammatory state and reduced immune response, related to excess adipose tissue. Virus interaction with ACE2 receptors and renal ectopic lipid retention are key issues in this context. Objective. To analyze the specific features of obesity that increase susceptibility to severe COVID-19 symptoms, from articles published between 2020 and 2022, and to promote future research. Methodology. A systematic review of original articles between 2020 and 2022 was conducted using key terms and Boolean operators in databases such as PubMed, Scopus, ProQuest, etc. Non-original studies were excluded to obtain more specific research. Results. Of 180 articles found, 42 were selected. Among these, it was highlighted that obese patients, especially elderly men, presented severe complications. However, young people with severe obesity and people with low weight also showed a higher risk of mortality. Decreased lung function, low vitamin D levels, and altered ACE2 were implicated in the severity of infection. Obesity-associated hyperglycemia increased the risk of ICU admission and mechanical ventilation, while insulin resistance worsened prognosis. Conclusion. Obesity emerges as an important risk factor for severity and mortality due to COVID-19, pointing to the need for specific attention to this group of patients and further research in the area.

As pessoas obesas enfrentam maiores complicações para contrair o SARS-CoV-2 devido ao seu estado pró-inflamatório crônico e à resposta imunológica reduzida, relacionados ao excesso de tecido adiposo. A interação do vírus com os receptores ACE2 e a retenção ectópica renal de lipídios são questões fundamentais nesse contexto. Objetivo. Analisar as características específicas da obesidade que aumentam a suscetibilidade a sintomas graves da COVID-19, com base em artigos publicados entre 2020 e 2022, e promover pesquisas futuras. Metodologia. Foi realizada uma revisão sistemática de artigos originais entre 2020 e 2022 usando termos-chave e operadores booleanos em bancos de dados como PubMed, Scopus, ProQuest, etc. Estudos não originais foram excluídos para obter pesquisas mais específicas. Resultados. Dos 180 artigos encontrados, 42 foram selecionados. Entre eles, destacou-se que os pacientes obesos, especialmente os homens mais velhos, apresentaram complicações graves. No entanto, jovens gravemente obesos e pessoas abaixo do peso também apresentaram maior risco de mortalidade. A diminuição da função pulmonar, os baixos níveis de vitamina D e a alteração da ACE2 foram implicados na gravidade da infecção. A hiperglicemia associada à obesidade aumentou o risco de internação na UTI e de ventilação mecânica, enquanto a resistência à insulina piorou o prognóstico. Conclusões. A obesidade surge como um importante fator de risco para a gravidade e a mortalidade da COVID-19, apontando para a necessidade de atenção específica a esse grupo de pacientes e de mais pesquisas na área.

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AIMS: Our cost-of-illness (COI) model adopted payer and societal perspectives over five years to measure the economic burden of Systemic Lupus Erythematosus (SLE) in Colombia. MATERIALS AND METHODS: A prevalence-based model was constructed to estimate costs and economic consequences for SLE patients in Colombia. The model included four health states: three phenotypes of SLE representing mild, moderate, and severe states and death. The clinical inputs were captured from the published literature and validated by the Delphi panel. Our model measured direct medical and indirect costs, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed. RESULTS: The number of Colombian SLE patients was 37,498. The number of SLE patients with mild, moderate, and severe phenotypes was 5343, 28757 and 3,397, respectively. SLE-patients with moderate (Colombian pesos; COP 146 billion) and severe phenotypes (COP276 billion) incurred higher costs than those with mild phenotypes (COP2 billion), over 5 years. The total SLE cost in Colombia over five years from the payer and societal perspectives was estimated to be COP 915 billion and 8 trillion, respectively. The costs per patient per year from the payer and societal perspectives were COP 4,881,902 ($3,510) and COP 46,637,054 ($33,528), respectively. CONCLUSION: The burden of SLE in Colombia over five years is substantially high, mainly due to the consequences of economic loss because it affects women and men of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Our COI indicated that disease management costs among patients with moderate and severe SLE were substantially higher than those among patients with a mild phenotype. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatment strategies that help in disease control.

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BACKGROUND: Basal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology. METHODS: An analytical cross-sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin-embedded samples with PTCH1 antibodies. Semi-quantitative analysis was performed to determine the expression level in the immunostained cells. RESULTS: We did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic-clinical characteristics (p > 0.05). CONCLUSION: The studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

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Introducción: La biopsia percutánea se ha convertido, en nuestros días, en el método diagnóstico más utilizado para la evaluación de las lesiones de mama sospechosas de malignidad. Objetivo: Caracterizar los resultados de biopsia por trucut en pacientes con categorías BI-RADS 4 y 5 sin criterio quirúrgico. Materiales y métodos: Se realizó un estudio observacional, descriptivo y transversal de 70 pacientes que presentaron lesión sospechosa de malignidad por ultrasonografía y que requirieron la realización de biopsia por aguja gruesa de la imagen reportada, entre enero de 2019 y diciembre de 2020. Se realizaron en la Consulta de Intervencionismo Mamario del Departamento de Imagenología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. Se analizaron las variables edad, categoría BI-RADS, resultado histopatológico, tamaño tumoral y complicaciones. Resultados: El grupo etario predominante fue el de 70-79 años (27,1). Se clasificaron 48 pacientes con categoría BI-RADS 5, para un 68,6 %. El carcinoma ductal infiltrante resulto ser el tipo histológico predominante, con 40 pacientes, representando el 57,1 % del total. Se obtuvo una media de 28,91 mm de diámetro de las lesiones biopsiadas. Todas las muestras resultaron útiles, aun en diámetros transversales inferiores a 2 cm. En la serie, las complicaciones reportadas fueron escasas. Conclusiones: La biopsia realizada con aguja gruesa bajo guía ecográfica con técnica de manos libres, es un método confiable para el diagnóstico de cáncer de mama, seguro y sin complicaciones graves. Se confirma que la categoría BI-RADS 5 coincide con diagnóstico histopatológico de cáncer mamario.

Introduction: Percutaneous biopsy has become, nowadays, the most used diagnostic method to evaluate breast lesions suspected of malignancy. Objective: To characterize the Tru-cut biopsy results in patients with BI-RADS 4 and 5 categories without surgical criteria. Materials and methods: An observational, descriptive and cross-sectional study was carried out between January 2019 and December 2020 on 70 patients who presented who presented a lesion suspicious of malignancy by ultrasonography and required a thick-needle biopsy of the reported image. They were performed at the Breast Intervention Clinic of the Imaging Department of the Clinical Surgical University Hospital Comandante Faustino Pérez Hernández, from Matanzas. The variables age, BI-RADS category, histopathological result, tumor size and complications were analyzed. Results: The predominant age group was the 70-79 years-old one (27.1). 48 patients were classified with BI-RADS 5 category, for 68.6%. Infiltrating ductal carcinoma resulted the predominant histological type, with 40 patients representing 57.1% of the total. An average diameter of 28.91 mm was obtained from the biopsied lesions. All samples were useful, even in transverse diameters less than 2cm. In the series, few complications were reported. Conclusion: Biopsy performed with thick needle under ultrasound guidance with free-hands technique, is a reliable method for breast cancer diagnosis, safe and without serious complications. It is confirmed that BI-RADS 5 category coincides with breast cancer pathological diagnosis.

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Introducción: El estudio de la comorbilidad requiere de un enfoque multilateral con vistas a mejorar la calidad de la atención de los enfermos por el sistema de atención. Objetivos: Explorar la magnitud de la comorbilidad de enfermedades crónicas en adultos internados en los hospitales. Métodos: Se realizó un estudio prospectivo-observacional-longitudinal-analítico. Se incluyeron pacientes internados en las Salas de Clínica Médica o pacientes clínicos en Salas de Internación Indiscriminada. Se realizó un estudio multicéntrico en 42 centros en un período de 2 años, con un muestreo consecutivo. Para el estudio se tuvo en cuenta la estadística descriptiva, inferencial y de regresión. Resultados: El total de pacientes en el estudio fue de 5925, masculinos con el 50,3 por ciento de edad 60,66 ± 0,25 años. Principal procedencia desde la guardia el 73 por ciento. La estadía hospitalaria de 12,61 ± 0,24 días, mayormente en pacientes quirúrgicos (15,45 ± 0,67 vs 11,76 ± 0,23; p < 0,00001). El 23 por ciento recibió tratamiento quirúrgico. El principal nivel educativo: secundario completo 21,6 por ciento. Dificultades económicas: 20 por ciento, mortalidad 9,26 por ciento; prevalencia de dislipemia, diabetes e hipertensión: 22,53 por ciento; 28,82 por ciento y 51,86 por ciento con 473 nuevos diagnósticos, IMC: 27,88 ± 0,65, Charlson global 2,09 ± 0,02 y en óbitos 3,84 ± 0,11. La media de patologías por paciente fue de 2,14 ± 0,01 y aumentó con la edad (p valor regresión lineal < 0,00001). Conclusiones: La hipertensión, la diabetes y la dislipemia representaron las entidades más prevalentes en Salas de Internación Clínica, Las enfermedades cardiovasculares, respiratorias, infectológicas, oncológicas, neurológicas, metabólicas y nefrológicas fueron predictores independientes de mortalidad(AU)

Introduction: The study of comorbidity requires a multilateral approach with a view to improving the quality of care for these patients by the care system. Objectives: To explore the magnitude of the comorbidity of chronic diseases in adults admitted to hospitals. Methods: Prospective-observational-longitudinal-analytical study. Patients hospitalized in a medical clinic room or clinical patients in indiscriminate hospitalization rooms are included, Multicenter study in 42 centers, with 2 years of recruitment. Consecutive sampling. Descriptive, inferential and regression statistics. Results: 5925 recruited, male gender 50,3percent, age 60,66 ± 0,25 years, main origin from the guard 73percent, stay 12,61 ± 0,24 days, longer in surgical (15,45 ± 0,67 vs 11,76 ± 0,23, p < 0,00001), 23percent received surgical treatment. Main educational level: complete secondary school 21,6%. Economic difficulties: 20percent, mortality 9,26percent, prevalence of dyslipidemia, diabetes and hypertension: 22,53percent, 28,82percent and 51,86percent with 473 new diagnoses in said pathologies, BMI: 27,88 ± 0,65, Global Charlson 2,09 ± 0,02 and in deaths 3,84 ± 0,11. The average number of pathologies per patient was 2,14 ± 0,01 and increased with age (p value for linear regression < 0,00001). Conclusions: Hypertension, diabetes and dyslipidemia represented the most prevalent entities in the clinical hospitalization room, cardiovascular, respiratory, infectious, oncological, neurological, metabolic and nephrological diseases were independent predictors of mortality(AU)

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BACKGROUND: Rickettsiae are obligate intracellular Gram-negative bacteria that are the causative agent of rickettsioses and are spread to vertebrate hosts by arthropods. There are no previous reports of isolation of Rickettsia amblyommatis for Colombia. METHODS: A convenience sampling was executed in three departments in Colombia for direct collection of adult ticks on domestic animals or over vegetation. Ticks were screened for the presence of Rickettsia spp. by real-time polymerase chain reaction (qPCR) amplifying the citrate synthase gene (gltA), and the positive sample was processed for isolation and further molecular characterization by conventional PCR. The absolute and relative frequencies were calculated for several tick species variables. All products from conventional PCR were further purified and sequenced by the Sanger technique. Representative sequences of 18 Rickettsia species were downloaded from GenBank. Consensus phylogenetic trees were constructed for the gltA, ompB, ompA, and htrA genes with 1000 replicates, calculating bootstrap values through the maximum likelihood method and the generalized time reversible substitution model in the MEGA 7.0 software program. RESULTS: One female Amblyomma mixtum collected on vegetation was amplified by qPCR (gltA), indicating a frequency of 1.6% (1/61) for Rickettsia spp. INFECTION: Sequence analysis of a rickettsial isolate from this tick in BLASTn showed 100% identity with gltA (340 base pairs [bp]), 99.87% for ompB (782 bp), 98.99% for htrA (497 bp), and 100% for ompA (488 bp) to R. amblyommatis. Concatenated phylogenetic analysis confirmed these findings indicating that the isolate is grouped with other sequences of Amblyomma cajennense complex from Panama and Brazil within the R. amblyommatis clade. CONCLUSIONS: This paper describes the isolation and early molecular identification of a R. amblyommatis strain from A. mixtum in Colombia.

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Monkeypox virus (MPXV) is an emerging zoonotic virus that belongs to the Orthopoxvirus genus and presents clinical symptoms similar to those of smallpox, such as fever and vesicular-pustular skin lesions. However, the differential diagnosis between smallpox and monkeypox is that smallpox does not cause lymphadenopathy but monkeypox generates swelling in the lymph nodes. Since the eradication of smallpox, MPXV has been identified as the most common Orthopoxvirus to cause human disease. Despite MPXV being endemic to certain regions of Africa, the current MPXV outbreak, which began in early 2022, has spread to numerous countries worldwide, raising global concern. As of the end of May 2023, over 87,545 cases and 141 deaths have been reported, with most cases identified in non-endemic countries, primarily due to human-to-human transmission. To better understand this emerging threat, this review presents an overview of key aspects of MPXV infection, including its animal reservoirs, modes of transmission, animal models, epidemiology, clinical and immunological features, diagnosis, treatments, vaccines, and prevention strategies. The material presented here provides a comprehensive understanding of MPXV as a disease, while emphasizing the significance and unique characteristics of the 2022 outbreak. This offers valuable information that can inform future research and aid in the development of effective interventions.

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Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).

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Introduction: The increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI. Material and methods: We studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. Results: -75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. Conclusions: The -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.

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Several arboviruses have emerged or reemerged into the New World during the past several decades, causing outbreaks of significant proportion. In particular, the outbreaks of Dengue virus (DENV), Zika virus, and Chikungunya virus (CHIKV) have been explosive and unpredictable, and have led to significant adverse health effects. These viruses are considered the leading cause of acute undifferentiated febrile illnesses in Colombia. However, Venezuelan equine encephalitis virus (VEEV) is endemic in Colombia, and arboviruses such as the Mayaro virus (MAYV) and the Oropouche virus (OROV) cause febrile illnesses in neighboring countries. Yet, evidence of human exposure to MAYV and OROV in Colombia is scarce. In this study, we conducted a serosurvey study in healthy individuals from the Cauca Department in Colombia. We assessed the seroprevalence of antibodies against multiple arboviruses, including DENV serotype 2, CHIKV, VEEV, MAYV, and OROV. Based on serological analyses, we found that the overall seroprevalence for DENV serotype 2 was 30%, 1% for MAYV, 2.6% for CHIKV, 4.4% for VEEV, and 2% for OROV. This study provides evidence about the circulation of MAYV and OROV in Colombia, and suggests that they-along with VEEV and CHIKV-might be responsible for cases of acute undifferentiated febrile illnesses that remain undiagnosed in the region. The study results also highlight the need to strengthen surveillance programs to identify outbreaks caused by these and other vector-borne pathogens.

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Background: Antitumor therapies targeting HER1/EGFR and HER2, such as monoclonal antibodies (MAbs) and tyrosine-kinase inhibitors (TKIs), have demonstrated a significant clinical benefit, but the emergence of resistance limits long-term efficacy. While secondary HER1 mutations confer tolerance to TKI, compensatory upregulation of HER2 drives resistance to anti-HER1 MAbs, which identifies MAb combinations targeting both receptors as an attractive therapeutic strategy. Nevertheless, toxicity hampers the clinical validation of this approach. Alternatively, cancer vaccines may induce antibodies directed against several antigens with less concern about induced toxicity. Methods: Polyclonal antibodies (PAbs) targeting HER1 and HER2 were induced in mice or rabbits through immunization. Recognition of different epitopes on targets by PAbs was validated by phage-display technology. Receptor downregulation was evaluated by flow cytometry, immunofluorescence, and Western blot. MTT assays assessed cytotoxicity, while the antitumor effect of PAbs was assayed in nude mice. Results: PAbs promoted degradation of HER1 and HER2 regarding clinical MAbs or their combinations. As a result, inhibition of cytotoxicity on tumor cell lines was improved, even in the presence of oncogenic mutations in HER1, as well as in cetuximab-insensitive cells. Accordingly, the antitumor effect of vaccination-induced PAbs was observed in lung tumor lines representative of sensitivity or resistance to HER1 targeting therapies. Conclusions: Immunization against HER1 and HER2 receptors offers an alternative to passive administration of combinations of MAbs, since vaccination-induced PAbs promote the downregulation of both receptors and they have a higher impact on the survival of tumor cells.

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Introduction: There is increasing evidence that immunohistochemical expression of p53, Ki-67, and Bcl-2 is associated with aggressive (aBCC) and less aggressive (nBCC) histological subtypes and may have a prognostic role. Aim: To investigate the clinicopathological features and immunohistochemical expressions of p53, Ki-67, and Bcl-2 in cutaneous basal cell carcinoma focusing on histological subtypes. Their roles and possible interactions in the development and progression of BCC are discussed. Material and methods: A total of 50 BCC samples from 50 patients from Western Mexico between June 2018 and June 2019 were included. Paraffin-embedded samples were immunostained with p53, Ki-67, and Bcl-2 antibodies. Semi-quantitative analysis was performed to determine the intensity and positivity of immunostained cells. Parametrical and non-parametrical tests were performed according to the sample's distribution. Results: Samples included 21 nBCC and 29 aBCC. The statistical analysis showed statistical association when grouped as non-aggressive and aggressive subtypes for p53 (p = 0.04) and Bcl-2 (p < 0.01). An inverse negative correlation was found between age and Bcl-2 expression. No statistical association was found between Ki-67 immunoreactivity and any of the other variables. Conclusions: We found that a high expression of Bcl-2 and a low expression of p53 was associated with more indolent histopathological features of BCC and therefore better outcomes. These findings suggest that examination of p53 and Bcl-2 expression in BCC patients may provide valuable prognostic information. These biomarkers may play a role in the development and progression of some cases of BCC.

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Here we describe the proteome of the fungus Hemileia vastatrix by label free mass spectrometry (LC-MS/MS). H. vastatrix is the causal agent of coffee rust disease, causing great economic losses in this crop. The objective of our work was to identify H. vastatrix proteins potentially involved in host colonization and infection, by exploring the shotgun proteomics approach. A total of 742 proteins were identified and are associated with several crucial molecular functions, biological processes, and cellular components. The proteins identified contribute to a better understanding of the metabolism of the fungus and may help identify target proteins for the development of specific drugs in order to control coffee rust disease. All data can be accessed at the Centre for Computational Mass Spectrometry - MassIVE MSV000087665 -https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=cc71ad75f767451abe72dd1ce0019387.

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BACKGROUND: Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single-nucleotide variants in the non-coding region could indirectly alter the expression and the function of the protein. OBJECTIVE: The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C > G; rs1049654;C > A, rs1334512;G > T, and rs3211892;G > A) in ACS patients from the western Mexican population. METHODS: We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme-linked immunosorbent assay. RESULTS: We show that rs1194182G > C variant provides a protective effect with a 1.7-fold lower susceptibility to develop ACS (p  = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST-segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p  = 0.038). Likewise, in diabetic patients versus non-diabetic (p < 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p  = 0.02). CONCLUSION: The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.

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Apolipoprotein B (APOB) is associated with the development of atherosclerosis and consequently in the acute coronary syndrome (ACS) physiopathology. Single number variants (SNVs) in apolipoprotein B gene (APOB) influence over the susceptibility for this syndrome. The aim of this study was to determine the impact of the rs1469513, rs673548, rs676210, and rs1042034 SNVs and serum levels of APOB in the risk of ACS in a population from western Mexico. We included 300 patients in the group of cases (ACSG) and 300 individuals in the control group (CG). APOB levels were evaluated by immunonephelometry, and SNVs were genotyped with TaqMan probes. We found significant allelic and genotypic differences between groups for rs673548 and rs676210 (OR = 1.33, p=0.030, OR = 2.69, p < 0.001) and rs1042034 (OR = 0.50, p=0.037) SNVs. We found a risk haplotype TAGT (OR: 2.14, IC 1.50-3.04, p < 0.001). Our findings support a significant risk association between rs673548 and rs676210 variants for ACS; meanwhile, rs1042034 could be considered protective factor in a western Mexican population. Also, in this population, haplotype TAGT may confer 2.14 times a higher risk. APOB serum levels were compared by genotype variants in both groups without any significant statistical difference.

Assuntos

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BACKGROUND: Thrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown. Our study explores the platelet (PLT) proteome from uncomplicated P. vivax patients, to fingerprint molecular pathways related to platelet function. Plasma levels of Platelet factor 4 (PF4/CXCL4) and Von Willebrand factor (VWf), as well as in vitro PLTs-P. vivax infected erythrocytes (Pv-IEs) interactions were also evaluated to explore the PLT response and effect on parasite development. METHODS: A cohort of 48 patients and 25 healthy controls were enrolled. PLTs were purified from 5 patients and 5 healthy controls for Liquid Chromatography-Mass spectrometry (LC-MS/MS) analysis. Plasma levels of PF4/CXCL4 and VWf were measured in all participants. Additionally, P. vivax isolates (n = 10) were co-cultured with PLTs to measure PLT activation by PF4/CXCL4 and Pv-IE schizonts formation by light microscopy. RESULTS: The proteome from uncomplicated P. vivax patients showed 26 out of 215 proteins significantly decreased. PF4/CXCL4 was significantly decreased followed by other proteins involved in platelet activation, cytoskeletal remodeling, and endothelial adhesion, including glycoprotein V that was significantly decreased in thrombocytopenic patients. In contrast, acute phase proteins, including SERPINs and Amyloid Serum A1 were increased. High levels of VWf in plasma from patients suggested endothelial activation while PF4/CXCL4 plasma levels were similar between patients and controls. Interestingly, high levels of PF4/CXCL4 were released from PLTs-Pv-IEs co-cultures while Pv-IEs schizont formation was inhibited. CONCLUSIONS: The PLT proteome analyzed in this study suggests that PLTs actively respond to P. vivax infection. Altogether, our findings suggest important roles of PF4/CXCL4 during uncomplicated P. vivax infection through a possible intracellular localization. Our study shows that platelets are active responders to P. vivax infection, inhibiting intraerythrocytic parasite development. Future studies are needed to further investigate the molecular pathways of interaction between platelet proteins found in this study and host response, which could affect parasite control as well as disease progression.

RESUMO

Mayaro virus (MAYV) is an alphavirus endemic to both Latin America and the Caribbean. Recent reports have questioned the ability of MAYV and its close relative, Chikungunya virus (CHIKV), to generate cross-reactive, neutralizing antibodies to one another. Since CHIKV was introduced to South America in 2013, discerning whether individuals have cross-reactive antibodies or whether they have had exposures to both viruses previously has been difficult. Using samples obtained from people infected with MAYV prior to the introduction of CHIKV in the Americas, we performed neutralizing assays and observed no discernable neutralization of CHIKV by sera from patients previously infected with MAYV. These data suggest that a positive CHIKV neutralization test cannot be attributed to prior exposure to MAYV and that previous exposure to MAYV may not be protective against a subsequent CHIKV infection.

Assuntos