Riesgo microbiológico de caries y factores predisponentes en mujeres gestantes / Microbiological caries risk and predisposing factors in pregnant women

La caries es una enfermedad multifactorial que afecta los tejidos duros del diente, con la evaluación del riesgo de caries es posible determinar la probabilidad de su incidencia durante un determinado periodo de tiempo. El objetivo consistió en determinar el estado de salud bucal en mujeres gestantes y su relación con factores de riesgo de caries. Se realizó un estudio descriptivo observacional clínico. La población estuvo constituida por mujeres gestantes que concurrieron al Hospital Ángela Llano de la cuidad de Corrientes para su atención. Se confeccionó una historia clínica y se determinó el estado de salud bucal y de riesgo de caries según protocolo CAMBRA. Para la carac- terización y descripción de los datos se utilizaron estadísticas univariadas. Los resultados alcanzados fueron: Índice de Caries de 4.5 a 6.5, en el índice de Placa la media ± DS 56,8% ± 39,9% Min: 28,5%/ Max: 90,9%. Respecto al valor de pH de 7,11 ±0,43, Min.: 7,00, Max.: 8,67. Flujo salival: media ± DS: 0,58ml/m ± 0,28 ml/m Min.:0,2 ml/m Max.: 0,62 ml/m; Edad promedio: 22años. Min.:18 Max.: 33 años. Recuento de Strepto- coccus mutans (SM) con periodo gestacional 1° y 2° trimestre, el conteo de bacterias: 2.3x105 +/- 3.2x 105 UFC/ml de saliva y 3° Trimestre el conteo de 1.2x 106 +/-2.02 x 106 UFC/ml de saliva. La presencia de SM puede aumentar considerable- mente el riesgo de caries, si los mecanismos de defen- sa del huésped no anulan la bacteria (AU)

Caries is a multifactorial disease that affects the hard tissues of the tooth. By evaluating the risk of caries, it is possible to determine the probability of its incidence during a certain period of time. The objective was to determine the oral health status of pregnant women and its relationship with caries risk factors. A clinical observational descriptive study was carried out. The population was made up of pregnant women who attended the Ángela Llano Hospital in the city of Corrientes for care. A clinical history was prepared, and the oral health status and caries risk were determined according to the CAMBRA protocol. Univariate statistics were used to characterize and describe the data. The results achieved were Caries Index from 4.5 to 6.5, in the Plaque index the mean ± SD 56.8% ± 39.9% Min: 28.5%/ Max: 90.9%. Regarding the pH value of 7.11 ±0.43, Min.: 7.00, Max.: 8.67. Salivary flow: mean ± SD: 0.58 ml/m ± 0.28 ml/m Min.: 0.2 ml/m Max.: 0.62 ml/m; Average age: 22 years. Min.:18 Max.: 33 years. Streptococcus mutans (SM) count with gestational period 1st and 2nd trimester, bacteria count: 2.3x105 +/- 3.2x 105 CFU/ml of saliva and 3rd Trimester count 1.2x 106 +/- 2.02 x 106 CFU/ml of saliva. The presence of SM can considerably increase the risk of caries, if the host defense mechanisms do not override the bacteria (AU)

Necrotizing fasciitis of the thigh secondary to perforated rectal cancer: the sciatic foramen as a route for infective spread.

Necrotizing fasciitis (NF) is a potentially life-threatening surgical emergency. It is a rapidly progressive infection of soft tissues, and mortality is related to the degree of sepsis and the general condition of the patient. It is a rare condition that requires a rapid diagnosis and surgical treatment is aggressive debridement. There are a small number of reported cases of perforation of a rectal malignancy leading to NF of the thigh. We present a case with rectal cancer in which the sciatic foramen had provided a channel for the spread of pelvic infection into the thigh.

La fascitis necrotizante es una emergencia quirúrgica potencialmente mortal. Es una infección de tejidos blandos rápidamente progresiva y la mortalidad está relacionada con el grado de sepsis y el estado general del paciente. Es una condición poco común que requiere un diagnóstico rápido, y el tratamiento quirúrgico consiste en un desbridamiento agresivo. Existe un pequeño número de casos notificados de perforación de neoplasia maligna de recto que conduce a fascitis necrotizante del muslo. Presentamos un caso de cáncer de recto en el cual el foramen ciático fue el canal para la propagación de la infección pélvica al muslo.

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

PSF-Radon transform algorithm: Measurement of the point-spread function from the Radon transform of the line-spread function.

In this article, we present a new method called point spread function (PSF)-Radon transform algorithm. This algorithm consists on recovering the instrument PSF from the Radon transform (in the line direction axis) of the line spread function (i.e., the image of a line). We present the method and tested with synthetic images, and real images from macro lens camera and microscopy. A stand-alone program along with a tutorial is available, for any interested user, in Martinez (PSF-Radon transform algorithm, standalone program). RESEARCH HIGHLIGHTS: Determining the instrument PSF is a key issue. Precise PSF determinations are mandatory if image improvement is performed numerically by deconvolution. Much less exposure time to achieve the same performance than a measurement of the PSF from a very small bead. Does not require having to adjust the PSF by an analytical function to overcome the noise uncertainties.

Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors.

Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%-42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.

Plant Regeneration of Agave cupreata by Somatic Embryogenesis in a Temporary Immersion System with Silver Nanoparticles.

Somatic embryogenesis in Agave genus has been induced; however, it is desirable to increase the rate of growth to get a more efficient propagation system. In this chapter, we present in detailed a protocol for somatic embryogenesis in Agave cupreata and the use of silver nanoparticles in a temporary immersion system. This is an efficient method that can be used commercially to improve the production and germination of somatic embryos.

The pro-oxidant action of high-oxygen MAP on beef patties can be counterbalanced by antioxidant compounds from common hawthorn and rose hips.

The objective of this research was to evaluate the effectiveness of antioxidant-rich extracts from rose hip (Rosa canina L.; RC) and hawthorn (Crataegus monogyna Jacq.; CM) at minimizing the oxidative damage to proteins and lipids in beef patties subjected to a high­oxygen (HiOx-MAP) and vacuum (Vacuum) packaging atmosphere. The extracts of RC and CM were characterized by quantifying bioactive compounds, namely, phenolic compounds, tocopherols and vitamin C. Both fruits had high concentrations of bioactive compounds, with RC having the highest total phenolic and vitamin C content. Yet, CM was the most efficient in protecting beef patties against protein carbonylation, reducing, as a result, the instrumental toughness in cooked beef patties. The use of CM and RC extracts in beef patties significantly improved consumer purchase intention in HiOx-MAP packaging systems. The use of CM and RC extracts or their combination in future research would be an effective antioxidant means to decrease the pro-oxidative effects caused by HiOx-MAP in red meat.

Effectiveness of Polyclonal Antibody Immunoconjugate Treatment with Propamidine Isethionate for Amoebic Keratitis in Golden Hamsters.

Acanthamoeba griffini is known to cause amoebic keratitis (AK); its main causes are inadequate hygiene when contact lenses are handled and/or its prolonged use at night, as well as the use of contact lenses during underwater activities. The most used treatment for AK is the combination of propamidine isethionate combined with polyhexamethylene biguanide, which disrupts the cytoplasmic membrane, and damages cellular components and respiratory enzymes. We proposed an immunoconjugate treatment obtained from Acanthamoeba immunized rabbit serum combined with propamidine isethionate; the corneas of hamsters inoculated with A. griffini (MYP2004) were treated with the combined, at 1, 2, and 3 weeks. Propamidine isethionate is frequently used for AK treatment, in vivo study we are found IL-1ß and IL-10 expression and caspase 3 activity is significantly increased with respect to the group that was inoculated with the amoeba without receiving any treatment, suggesting that it may be an effect of the toxicity of this drug on the corneal tissue. Application of the immunoconjugate showed enhanced amoebicidal and anti-inflammatory activities, with comparison to propamidine isethionate only. The aim of this study is to evaluate the effect of the immunoconjugate of propamidine isethionate and polyclonal antibodies as a treatment of AK in golden hamsters (Mesocricetus auratus).

Efecto del tratamiento de la morfología oclusal con materiales para restauraciones preventivas / Effect of treating occlusal morphology with materials for preventive restorations

Introducción: las fosas y fisuras son áreas formadas por delgadas irregularidades de la capa del esmalte de la superficie oclusal. La compleja morfología en dientes posteriores es un determinante biológico asociado al desarrollo de caries. Objetivo: evaluar el efecto de diversas formas de tratar la morfología oclusal en la adaptación y penetración de materiales utilizados en restauraciones preventivas. Material y métodos: diseño experimental e in vitro. Sesenta terceros molares fueron distribuidos aleatoriamente en dos grupos: surco sin ameloplastia y con ameloplastia; además, contaban con acondicionamiento del esmalte que se subdividió en tres subgrupos: 1) sellador de fosas y fisuras, 2) adhesivo/sellador de fosas y fisuras y 3) adhesivo/ resina Flow. Resultados: los subgrupos adhesivo/sellador y adhesivo/ Flow alcanzaron mayores valores de adaptación íntima a las paredes del surco. Las diferencias fueron significativas entre los materiales (p = 0.0009). Las mayores zonas de desadaptación resultaron para el sellador sin y con ameloplastia. La penetración de los materiales fue mayor en los surcos con ameloplastia. En los surcos tratados con ameloplastia, el adhesivo/Flow reveló el mayor porcentaje de penetración y la mejor adaptación a las paredes del surco. Conclusiones: la penetración del material está positivamente correlacionada con la profundidad del surco. El sellador con y sin ameloplastia mostró pobre adaptación a las paredes del surco (AU)

Introduction: pits and fissures are areas formed by fine irregularities in the enamel layer of the occlusal surface. The complex morphology in posterior teeth are biological determinants associated with the development of caries. Objective: to evaluate the effect of various ways of treating occlusal morphology on the adaptation and penetration of materials used in preventive restorations. Material and methods: experimental design, in vitro. Sixty third molars were randomly distributed into two groups: groove without ameloplasty and with ameloplasty, with enamel conditioning with three subgroups: 1) pit and fissure sealer, 2) adhesive/pit and fissure sealer, 3) adhesive/resin flow. Results: the adhesive/sealant and adhesive/flow subgroups reached higher values of intimate adaptation to the furrow walls. The differences were significant between the materials (p = 0.0009). The largest areas of maladjustment were found for the sealant without and with ameloplasty. The penetration of the materials was greater in the grooves with ameloplasty. In the grooves treated with ameloplasty, the adhesive/flow revealed the highest percentage of penetration and the best adaptation to the walls of the groove. Conclusions: the penetration of the material is positively correlated with the depth of the furrow. The sealant with and without ameloplasty showed poor adaptation to the sulcus walls (AU)

The Use of Complementary and Alternative Medicine among Peritoneal Dialysis Patients at a Second-Level Hospital in Yucatán Mexico.

BACKGROUND: Complementary and alternative medicine (CAM) is widely used for multiple reasons such as treatment of diseases and their symptoms, empowerment, self-care, disease prevention, dissatisfaction, adverse effects or cost of conventional medicine, perception of compatibility with beliefs, and idiosyncrasy. This study investigated CAM use in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD). METHODS: A cross-sectional survey study was conducted with 240 eligible patients with CKD in the PD program. By applying the I-CAM-Q-questionnaire, the frequency, level of satisfaction, and reasons for CAM use were explored, and the demographic and clinical data of users and non-users were analyzed. Data analysis included descriptive analysis, Student's t-test, Mann-Whitney U, chi-square, and Fisher tests. RESULTS: The main types of CAM used were herbal medicine, and chamomile was the most commonly used. To improve the state of well-being was the main reason for use, the attributable benefit of CAM was high, and only a low percentage of users reported side effects. Only 31.8% of the users informed their physicians. CONCLUSION: The use of CAM is popular among renal patients, and physicians are not adequately informed; in particular, the CAM type ingested represents a risk for drug interactions and toxicity.

Choreiform movements and basal ganglia calcification as a presentation of Fahr's disease

Basal ganglia calcifications may be a radiological finding in approximately 20% of the general population. When they are associated with neuropsychiatric and motor symptoms in an idiopathic form, they are known as Fahr's disease. They are termed "Fahr's syndrome" when they are secondary to an identifiable and potentially treatable cause. In this report, we present the clinical case of a 69-year-old woman with the onset of subacute chorea, with no other associated symptoms, in whom extensive basal ganglia calcifications were found on neuroimaging, due to which metabolic disorders were subsequently ruled out. The objective is to contribute to the characterization of the potential motor manifestations which would give rise to clinical suspicion. Due to its low incidence and the little information on this condition in the region, we want to encourage documentation of other cases and the process for ruling out other differential diagnoses, in order to obtain more information on its actual epidemiology and signs and symptoms in Colombia. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2635).

Concordancia de los hallazgos citológicos, colposcópicos e histológicos en lesiones premalignas del cuello uterino / Concordance in cytological, colposcopic and histological findings in premalignant lesions of the cervix

Resumen OBJETIVO: Determinar la concordancia de los hallazgos citológicos, colposcópicos e histopatológicos en lesiones premalignas del cuello uterino. MATERIALES Y MÉTODOS: Estudio transversal, retrospectivo y comparativo, efectuado en la Clínica de Displasias del Hospital General Regional 1 del estado de Querétaro, México, del 1 de enero a diciembre del 2020, con base en la información de los expedientes de mujeres con reporte citológico, colposcópico e histopatológico (biopsia) de lesión intraepitelial de bajo y alto grado. El plan de análisis estadístico incluyó intervalos de confianza para promedios y porcentajes. Se utilizó el Índice de Kappa ponderado para conocer el nivel de concordancia. RESULTADOS: Se analizaron 290 expedientes. La edad promedio de las pacientes fue 36 años, el índice de kappa ponderado fue k = 0.41 (IC95%: 0.33-0.53) para la citología y la colposcopia con un valor moderado (regular). Para la citología y la biopsia fue de k= 0.33 (IC95%: 0.22-0.49) con un valor escaso (medio). En cuanto a la colposcopia y la biopsia fue de k = 0.61 (IC95%: 0.49-0.72) con un valor de buena (sustancial) concordancia. CONCLUSIÓN: Entre la citología y la colposcopia el coeficiente de concordancia fue moderado, para la citología y la biopsia fue escaso, mientras que para la colposcopia y la biopsia fue un sustancial.

Abstract OBJECTIVE: To determine the concordance in cytologic, colposcopic and histopathologic findings in premalignant lesions of the uterine cervix. MATERIALS AND METHODS: Cross-sectional, retrospective and comparative study, carried out in the dysplasia clinic of the Hospital General Regional 1 of the state of Querétaro, Mexico, from January 1 to December 2020, based on information from the records of women with cytology, colposcopy and histopathology (biopsy) report with low- and high-grade intraepithelial lesion. The statistical analysis plan included confidence intervals for averages and percentages. The weighted Kappa Index was used to determine the level of concordance. RESULTS: Two hundred and ninety records were analyzed. The mean age of the patients was 36 years, the weighted kappa index was k = 0.41 (95%CI: 0.33-0.53) for cytology and colposcopy with a moderate value (fair). For cytology and biopsy, it was k= 0.33 (95%CI: 0.22-0.49) with a poor value (medium). For colposcopy and biopsy, it was k = 0.61 (95%CI: 0.49-0.72) with a value of good (substantial) agreement. CONCLUSION: Between cytology and colposcopy the concordance coefficient was moderate, for cytology and biopsy it was poor, while for colposcopy and biopsy it was a substantial.

2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults - Brazilian Sleep Association.

Chronic insomnia disorder (simplified in this document as insomnia) is an increasingly common clinical condition in society and a frequent complaint at the offices of different areas of health practice (particularly Medicine and Psychology). This scenario has been accompanied by a significant evolution in treatment, as well as challenges in approaching patients in an appropriately way. This clinical guideline, coordinated by the Brazilian Sleep Association and the Brazilian Association of Sleep Medicine and counting on the active participation of various specialists in the area, encompasses an update on the diagnosis and treatment of insomnia in adults. To this end, it followed a structured methodology. Topics of interest related to diagnosis were written based on theoretical framework, evidence in the literature, and professional experience. As for the topics related to the treatment of insomnia, a series of questions were developed based on the PICO acronym (P - Patient, problem, or population; I - Intervention; C - Comparison, control, or comparator; O - Outcome). The work groups defined the eligible options within each of these parameters. Regarding pharmacological interventions, only the ones currently available in Brazil or possibly becoming available in the upcoming years were considered eligible. Systematic reviews were conducted to help prepare the texts and define the level of evidence for each intervention. The final result is an objective and practical document providing recommendations with the best scientific support available to professionals involved in the management of insomnia.

MES SV40 Cells Are Sensitive to Lipopolysaccharide, Peptidoglycan, and Poly I:C Expressing IL-36 Cytokines.

Mesangial cells (MC) maintain the architecture and cellular communication and indirectly join in the glomerular filtration rate for the correct functioning of the glomerulus. Consequently, these cells are activated constantly in response to changes in the intraglomerular environment due to a metabolic imbalance or infection. IL-36, a member of the IL-1 family, is a cytokine that initiates and maintains inflammation in different tissues in acute and chronic pathologies, including the skin, lungs, and intestines. In the kidney, IL-36 has been described in the development of tubulointerstitial lesions, the production of an inflammatory environment, and is associated with metabolic and mesangioproliferative disorders. The participation of IL-36 in functional dysregulation and the consequent generation of the inflammatory environment by MCs in the presence of microbial stimulation is not yet elucidated. In this work, the MES SV40 cell cultures were stimulated with classical pathogen-associated molecular patterns (PAMPs), mimicking an infection by negative and positive bacteria as well as a viral infection. Lipopolysaccharide (LPS), peptidoglycan (PGN) microbial wall components, and a viral mimic poly I:C were used, and the mRNA and protein expression of the IL-36 members were assessed. We observed a differential and dose-dependent IL-36 mRNA and protein expression under LPS, PGN, and poly I:C stimulation. IL-36ß was only found when the cells were treated with LPS, while IL-36α and IL-36γ were favored by PGN and poly I:C stimulation. We suggest that the microbial components participate in the activation of MCs, leading them to the production of IL-36, in which a specific member may participate in the origin and maintenance of inflammation in the glomerular environment that is associated with infections.

Specialized acyl carrier protein used by serine palmitoyltransferase to synthesize sphingolipids in Rhodobacteria.

Serine palmitoyltransferase (SPT) catalyzes the first and committed step in sphingolipid biosynthesis condensating L-serine and acyl-CoA to form 3-oxo-sphinganine. Whenever the structural gene for SPT is present in genomes of Rhodobacteria (α-, ß-, and γ-Proteobacteria), it co-occurs with genes coding for a putative acyl carrier protein (ACP) and a putative acyl-CoA synthetase (ACS). In the α-proteobacterium Caulobacter crescentus, CC_1162 encodes an SPT, whereas CC_1163 and CC_1165 encode the putative ACP and ACS, respectively, and all three genes are known to be required for the formation of the sphingolipid intermediate 3-oxo-sphinganine. Here we show that the putative ACP possesses a 4'-phosphopantetheine prosthetic group, is selectively acylated by the putative ACS and therefore is a specialized ACP (AcpR) required for sphingolipid biosynthesis in Rhodobacteria. The putative ACS is unable to acylate coenzyme A or housekeeping ACPs, but acylates specifically AcpR. Therefore, it is a specialized acyl-ACP synthetase (AasR). SPTs from C. crescentus, Escherichia coli B, or Sphingomonas wittichii use preferentially acyl-AcpR as thioester substrate for 3-oxo-sphinganine synthesis. Whereas acyl-AcpR from C. crescentus is a good substrate for SPTs from distinct Rhodobacteria, acylation of a specific AcpR is achieved by the cognate AasR from the same bacterium. Rhodobacteria might use this more complex way of 3-oxo-sphinganine formation in order to direct free fatty acids toward sphingolipid biosynthesis.

Infección por COVID-19 en pacientes oncológicos y asociación con el tratamiento recibido / COVID-19 infection in cancer patients and association with the antineoplastic treatment

Resumen La evidencia que relaciona la terapia oncológica con la incidencia por COVID-19 varía según el tipo de terapia administrada. La incidencia informada en pacientes que reciben tratamiento oncológico varía entre 1 y 4%. El objetivo del presente estudio fue determinar la incidencia por COVID-19 en pacientes oncológicos en tratamiento activo y evaluar si existe asociación con el esquema recibido. Se utilizó una cohorte retrospectiva que incluyó de forma consecutiva a los pacientes adultos que realizaron tratamiento ambulatorio desde marzo/2020 hasta abril/2021 en un Hospital Público de referencia. El evento principal fue el diagnóstico confirmado de COVID-19. La asociación con los tratamientos oncológicos fue evaluada mediante regresión logís tica multivariada ajustando por edad, sexo, localización del tumor, cobertura de salud y localidad de residencia. Se incluyeron 463 pacientes, mediana de edad 58 años (RIC = 47-66), 73.3% (n = 337) mujeres. La incidencia de COVID-19 fue 5.6% (n = 26) con una tasa de mortalidad del 12% (n = 3). El riesgo de infección fue mayor en los que estaban realizando tratamiento únicamente con anticuerpos monoclonales, 14.3% vs. 4.9% (OR-ajustado = 3.3, p = 0.03) y aquellos en tratamiento con inhibidores de puntos de control inmunológicos, 23.1% vs. 5.1% (OR-ajustado = 5.8, p = 0.03). La quimioterapia citotóxica, sola o en combinación con anticuerpos mo noclonales, no presentó mayor riesgo de infección. La edad, sexo, sitio tumoral, cobertura de salud y localidad de residencia no se asoció con la incidencia de COVID-19. En base a nuestros resultados, el tratamiento con anticuerpos monoclonales o inhibidores de puntos de control inmunológicos se asoció con mayor incidencia de infección por COVID-19.

Abstract Evidence linking anticancer therapy with the incidence of COVID-19 varies according to the type of therapy administered. The reported COVID-19 incidence in patients receiving antineoplastic treatment varies between 1 and 4%. The aim of this study was to determine the incidence of COVID-19 in cancer patients under active treatment and to assess whether there is an association with the received anticancer therapy. It was a retrospective cohort that consecutively included adult outpatients who underwent treatment in a referral center from March 2020 to April 2021. The primary endpoint was the confirmed diagnosis of COVID-19. The association with anticancer treatments was evaluated using multivariate logistic regression adjusting for age, sex, tumor site, health coverage status, and place of residence. The sample included 463 patients, the median age was 58 years (IQR = 47-66), 73.3% (n = 337) were women. The incidence of COVID-19 was 5.6% (n = 26) with a mortality rate of 12% (n = 3). The risk of infection was higher in patients undergoing treatment only with monoclonal antibod ies, 14.3% vs. 4.9% (adjusted OR = 3.3, p = 0.03) and those in treatment with immunotherapy, 23.1% vs. 5.1% (adjusted OR = 5.8, p = 0.03). Cytotoxic chemotherapy, alone or in combination with monoclonal antibodies, did not present an increased risk of infection. Age, sex, tumor site, health coverage, and place of residence did not show association with the incidence of COVID-19. Based on our results, treatment with monoclonal antibodies or immunotherapy was associated with a higher rate of COVID-19 infection while chemotherapy did not modify the incidence of COVID-19.

Distribution of human papillomavirus genotypes by severity of cervical lesions in HPV screened positive women from the ESTAMPA study in Latin America.

The proportion of HPV16 and 18-associated cervical cancer (CC) appears rather constant worldwide (≥70%), but the relative importance of the other HR-HPV differs slightly by geographical region. Here, we studied the HPV genotype distribution of HPV positive Latin American (LA) women by histological grade, in a sub-cohort from the ESTAMPA study; we also explored the association of age-specific HPV genotypes in severe lesions. Cervical samples from 1,252 participants (854 ≤CIN1, 121 CIN2, 194 CIN3 and 83 CC) were genotyped by two PCRs-Reverse Blotting Hybridization strategies: i) Broad-Spectrum General Primers 5+/6+ and ii) PGMY9/11 PCRs. HPV16 was the most frequently found genotype in all histological grades, and increased with the severity of lesions from 14.5% in ≤ CIN1, 19.8% in CIN2, 51.5% in CIN3 to 65.1% in CC (p < 0.001). For the remaining HR-HPVs their frequency in CC did not increase when compared to less severe categories. The nonavalent vaccine HR-types ranked at the top in CC, the dominant ones being HPV16 and HPV45. HR-HPV single infection occurs, respectively, in 57.1% and 57.0% of ≤CIN1 and CIN2, increasing to 72.2% and 91.6% in CIN3 and CC (p<0.001). No association between age and HPV type was observed in CC, although the risk of HPV16 infection in CIN3 cases increased with age. Results confirm the relevance of HPV16 in the whole clinical spectrum, with a strong rise of its proportion in CIN3 and cancer. This information will be relevant in evaluating the impact of HPV vaccination, as a baseline against which to compare genotype changes in HPV type-specific distribution as vaccinated women participate in screening in LA region. Likewise, these data may help select the best HPV testing system for HPV-based efficient, affordable, and sustainable screening programmes.

Low Concentration of the Neutrophil Proteases Cathepsin G, Cathepsin B, Proteinase-3 and Metalloproteinase-9 Induce Biofilm Formation in Non-Biofilm-Forming Staphylococcus epidermidis Isolates.

Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap+, icaA−, icaD− genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p < 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p < 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation.

The Protective Role of pVHL in Imiquimod-Induced Psoriasis-like Skin Inflammation.

Psoriasis is a chronic inflammatory disease distinguished by an excessive proliferation and abnormal differentiation of keratinocytes. Immune cells, such as T lymphocytes and neutrophils, and inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and interleukin 17 (IL-17), are essential for maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin promotes the expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α). This protein regulates the expression of angiogenic and glycolytic factors, such as vascular endothelial grown factor and lactate dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel-Lindau protein (pVHL) is a negative regulator of HIF-1α. Previously, we found that pVHL was almost absent in the lesions of psoriasis patients; therefore, we investigated the impact of rescue pVHL expression in lesional skin. We used the imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed us to express pVHL in the skin. Our data show that, in lesional skin, pVHL expression was reduced, whereas HIF-1α was increased. Remarkably, the retrieval of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal and vascular thickness. Furthermore, pVHL expression was capable of reducing HIF-1α, LDH, TNF-α and immune cell infiltration (mainly IL-17+ neutrophils). In conclusion, our results demonstrate that pVHL has a protective role to play in the pathophysiology of psoriasis.