Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour. Our aim was to evaluate and quantify the physico-chemical properties of the PDAC TME. Both cellularized (native TME) and decellularized (tECM) patient-derived PDAC xenografts were analyzed. A factorial design of experiments identified an optimal combination of factors for effective xenograft decellularization. Our results provide a complete advance in our understanding of the PDAC TME and its corresponding stroma, showing that it presents an interconnected porous architecture with very low permeability and small pores due to the contractility of the cellular components. This fact provides a potential therapeutic strategy based on the therapeutic agent size.

Antimicrobial Efficacy of the Use of Mouthwash with Cetylpiridinium Chloride for Aerosol Producing Procedures. A Systematic Review / Eficacia antimicrobiana del uso del enjuague bucal con cloruro de cetilpiridinio en procedimientos que generan aerosoles. Revisión sistemática

Abstract The present research aims to determine the antimicrobial efficacy of the mouthwashes based on cetylpyridinium chloride (CPC), before aerosol producing dental procedures. A data search was performed during August 2021 in five databases MEDLINE (PubMed), SCOPUS, SCIELO, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Randomized clinical trials (RCTs) were included based on the PICO question, comparing the efficacy of the mouthwashes based on cetylpyridinium chloride (CPC), versus other mouthwashes and water, before aerosol producing dental procedures, papers in English, Spanish and Portuguese were included without time limits. The risk of the included studies was evaluated with the tool RoB 2.0. Number of registration PROSPERO N° CRD42021275982. 120 papers were obtained in the preliminary search, discarding those that didn't comply with the selection criteria, leaving only 3 studies. These papers reported the use of cetylpyridinium chloride (CPC) was effective for the reduction of bacteria during the ultrasonic prophylactic procedure. The use of CPC mouthwashes previous to the dental treatment with ultrasonic prophylaxis showed only antibacterial capacity.

Resumen El presente trabajo de investigación tiene como objetivo determinar la eficacia antimicrobiana de los colutorios a base de cloruro de Cetilpiridinio (CPC), previo a tratamientos dentales que generen aerosol. Se realizó una búsqueda bibliográfica hasta agosto del 2021 en cinco bases de datos: MEDLINE (vía PubMed), SCOPUS, SCIELO, Cochrane Central Register of Controlled Trials (CENTRAL) y Google Scholar. Se incluyeron ensayos clínicos aleatorizados (ECAs), basándose en la pregunta PICOS, que compare la eficacia del colutorio a base de cloruro de Cetilpiridinio (CPC) con otro colutorio, placebo o agua, previo a un tratamiento dental que genere aerosol, en los idiomas español, inglés o portugués y sin límite de tiempo. El riesgo de los estudios incluidos se evaluó con la herramienta RoB 2.0. Número de registro PROSPERO N° CRD42021275982. Se obtuvo un total de 120 artículos en la búsqueda preliminar, descartando aquellos que no cumplían con los criterios de selección, quedando sólo 3articulos. Estos artículos informaron que el uso de CPC es efectivo para la reducción de bacterias durante el procedimiento de profilaxis con ultrasonido. El uso de los enjuagues bucales a base de CPC previo al tratamiento dental de profilaxis con ultrasonido sólo tiene eficacia antibacteriana.

Comparison among three predictive models for cancer-associated thromboembolism in a hispanic population.

In this study we aimed to evaluate and compare the overall performance of the Khorana, PROTECHT, and CONKO scores as predictive scores for the occurrence of venous thromboembolism (VTE) among ambulatory Hispanic patients with solid tumors. We included all outpatients with newly diagnosed solid tumors receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. For each patient the Khorana, PROTECHT, and CONKO scores were calculated at the beginning of treatment. The sixth-month cumulative incidence of VTE was estimated using the Fine & Gray competing risk model. The receiver operating characteristic (ROC) curve was used to assess the performance of each predictive tool through the analysis of the c-statistic, sensitivity, and specificity. A total of 708 patients were included in the research. After a median follow-up of 8.13 months, the cumulative VTE incidence at six months was 4.45% (95%CI: 3.25-6.91%) for the overall population. At the conventional positivity threshold of 3 points, these scores classified from 17.7 to 32.5% of all patients as high-risk for VTE. Patients belonging to the high-risk category of the Khorana, PROTECHT, and CONKO scores had significantly higher risk of VTE in comparison to low-risk patients (Khorana score: Hazard Ratio (HR): 2.66; 95%CI:1.20-5.89; p = 0.042; PROTECHT score: HR: 3.44; 95%CI:1.63-7.21; p = 0.001; CONKO score HR: 3.68; 95%CI:1.72-7.85; p = 0.001). The c-statistic of the ROC curve was: 0.62 (95%CI: 0.52-0.72), 0.62 (95%CI: 0.52-0.73), and 0.65 (95%CI: 0.56-0.76) for the Khorana, PROTECHT, and CONKO scores, respectively; with similar sensitivity (range: 67-70%) and specificity (range: 52-62%) among them. For Hispanic patients with solid tumors the Khorana, PROTECHT, and CONKO scores accurately categorize their risk of VTE. However, the overall discriminatory performance of these models remains poor (c-statistic from 0.62 to 0.65) for predicting all patients at risk for thromboembolic events.

Composición de especies vegetales en un matorral desértico rosetófilo del norte de Coahuila, México / Plant species composition in a rosetophyllous desert scrub of northern Coahuila, Mexico

RESUMEN El Área de Protección de Flora y Fauna (APFF) Maderas del Carmen, ubicada en el estado de Coahuila, se considera un reservorio natural para el matorral rosetófilo, el cual ha sido afectado por el cambio de uso de suelo en el norte de México. El objetivo del presente trabajo fue describir el estado actual del matorral desértico rosetófilo del Área Protegida de Flora y Fauna Maderas del Carmen, con base en su estructura, composición florística y diversidad. Se evaluó la vegetación mediante 35 parcelas de 5 m x 5 m en 7 transectos lineales. Se midió altura (m), diámetro (cm) y área de copa (m2). Se determinó abundancia, dominancia y frecuencia de cada especie para obtener el índice de valor de importancia (IVI), además del índice de entropía de Shannon (H´) para conocer la diversidad, y la diversidad verdadera de Shannon (1D). Se registraron 31 familias, 61 géneros y 70 especies de plantas vasculares, incluyendo una endémica de México (Galactia brachystachys) y a 20 bajo estatus de protección, como Agave havardiana, que además, es especie vulnerable. Las familias con mayor riqueza fueron Fabaceae, Asteraceae, Asparagaceae y Cactaceae. Las formas biológicas y de vida fueron árboles y arbustos (48 %), hierbas (36 %), suculentas (13 %) y trepadoras (3 %). El H´ fue de 3.13 y la 1D de 22.87. El matorral rosetófilo del APFF Maderas del Carmen tiene una diversidad media-alta, está dominado por Agave lechuguilla Torr., con mayor abundancia e IVI. La composición florística y la diversidad encontrada permite una línea base para estudios posteriores que determinen el estatus ecológico de la zona. Especialmente para conocer con mayor detalle la dinámica poblacional de las especies endémicas y bajo estatus de protección, además del hábitat para la fauna silvestre presente en el APFF Maderas del Carmen.

ABSTRACT The Maderas del Carmen Flora and Fauna Protection Area (APFF), located in the state of Coahuila, is considered a natural reservoir for rosetophyllous scrub, which has been affected by land use change in northern Mexico. The objective of this work was to describe the current state of the rosetophilous desert scrub in the Maderas del Carmen Flora and Fauna Protected Area, based on its structure, floristic composition, and diversity. Vegetation was evaluated using 35 plots of 5 m x 5 m in 7 linear transects. Height (m), diameter (cm) and crown area (m2) were measured. Abundance, dominance and frequency of each species were determined to obtain the importance value index (IVI), in addition to the Shannon entropy index (H´) to know the diversity, and the true diversity of Shannon (1D). 31 families, 61 genera and 70 species of vascular plants were recorded, including one endemic to Mexico (Galactia brachystachys) and 20 under protection status, such as Agave havardiana, which is also a vulnerable species. The richest families were Fabaceae, Asteraceae, Asparagaceae and Cactaceae. Biological and life forms were trees and shrubs (48 %), herbs (36 %), succulents (13 %), and climbers (3 %). The H' was 3.13 and the 1D was 22.87. The rosetophilous scrub of the APFF Maderas del Carmen has a medium-high diversity, it is dominated by Agave lechuguilla Torr., with greater abundance and IVI. The floristic composition and the diversity found allow a baseline for subsequent studies that determine the ecological status of the area. Especially, they allow us to know in greater detail the population dynamics of endemic species and under protection status, in addition to the habitat for wildlife present in the APFF Maderas del Carmen.

Proteome Dynamics of Persulfidation in Leaf Tissue under Light/Dark Conditions and Carbon Deprivation.

Hydrogen sulfide (H2S) acts as a signaling molecule in plants, bacteria, and mammals, regulating various physiological and pathological processes. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. This research aimed to study the regulation of protein persulfidation. We used a label-free quantitative approach to measure the protein persulfidation profile in leaves under different growth conditions such as light regimen and carbon deprivation. The proteomic analysis identified a total of 4599 differentially persulfidated proteins, of which 1115 were differentially persulfidated between light and dark conditions. The 544 proteins that were more persulfidated in the dark were analyzed, and showed significant enrichment in functions and pathways related to protein folding and processing in the endoplasmic reticulum. Under light conditions, the persulfidation profile changed, and the number of differentially persulfidated proteins increased up to 913, with the proteasome and ubiquitin-dependent and ubiquitin-independent catabolic processes being the most-affected biological processes. Under carbon starvation conditions, a cluster of 1405 proteins was affected by a reduction in their persulfidation, being involved in metabolic processes that provide primary metabolites to essential energy pathways and including enzymes involved in sulfur assimilation and sulfide production.

Consecuencias físicas y psicológicas de la violencia obstétrica en países de Latinoamérica / Physical and psychological consequences of obstetric violence in Latin American countries

El término violencia obstétrica tiene sus orígenes en Latinoamérica, se considera una expresión de violencia de género y de violencia institucional contra la mujer. Puede ser ejercida de dos maneras, física y psicológica, por lo que se pretende definir la violencia obstétrica, su origen, divisiones, relación con los derechos sexuales y reproductivos de la mujer, así como identificar sus consecuencias físicas y psicológicas. Se realizó una búsqueda bibliográfica en Medigraphic, SciELO y Google Académico, fueron incluidas únicamente las publicaciones que se encontraron a texto completo, en español, inglés y portugués durante los años 2014 al 2022. La violencia obstétrica provoca que los derechos sexuales y reproductivos de las mujeres sean quebrantados, lo que hace imprescindible que todos los involucrados en la atención en salud conozcan las repercusiones físicas y psicológicas relacionadas que contribuyen a la morbimortalidad de la madre y el recién nacido, tales como: desgarros vaginales, problemas en la lactancia materna, síndrome de estrés postraumático y depresión posparto

The term obstetric violence has its origins in Latin America, it is considered an expression of gender violence and institutional violence against women. It can be exercised in two ways, physical and psychological, therefore, the aim is to define obstetric violence, its origin, divisions, and relation with women's sexual and reproductive rights, as well as to identify its physical and psychological consequences. A bibliographic search was conducted in Medigraphic, SciELO, and Google Scholar, including only publications that were found in full text, in Spanish, English, and Portuguese during the years 2014 to 2022. Obstetric violence causes the violation of women's sexual and reproductive rights, which makes it essential for all those involved in health care to be aware of the related physical and psychological repercussions that contribute to maternal and newborn morbidity and mortality, such as vaginal tears, breastfeeding problems, post-traumatic stress syndrome, and postpartum depression

Detection of protein persulfidation in plants by the dimedone switch method.

Hydrogen sulfide (H2S) is a well-known signaling molecule in both animals and plants, endogenously produced by cells, and involved in a wide variety of biological functions. In plants, H2S regulates a wide range of essential aspects of plant life, including plant responses to numerous stresses and physiological processes as important as abscisic acid (ABA)-dependent stomatal movement, photosynthesis, and autophagy. The best studied molecular mechanism responsible of sulfide signaling is protein persulfidation, a post-translational modification of cysteine residues, where a thiol group (P-SH) is transformed into a persulfide group (P-SSH). In this way, persulfidation has emerged as a new type of cellular redox mechanism that can regulate protein structure and function and interest in this modification has increased exponentially. However, the identification and the development of detection methods have been challenging. Nevertheless, on the basis of the chemical differences between the thiol and the persulfide groups, different methods have been implemented. In plants, different high-throughput proteomic analyzes have been performed using a tag-switch method where in the first step all thiols and persulfides are blocked and then in the second step persulfides are selectively labeled using a specific nucleophile. This chapter outlines a new method, previously described in mammals, that has been applied to detect persulfidation in plants and is based on the same chemical premise but consists of chemoselective persulfide labeling with dimedone-based probes. Here, we provide a detailed workflow of this method that includes procedures for the determination of the persulfidation level of a protein extract visualized and quantified by fluorescence on the gel on one side, and on the other, the labeling and purification of persulfidated proteins for identification by mass spectrometry.

A Revised Phylogenetic Classification for Viola (Violaceae).

The genus Viola (Violaceae) is among the 40-50 largest genera among angiosperms, yet its taxonomy has not been revised for nearly a century. In the most recent revision, by Wilhelm Becker in 1925, the then-known 400 species were distributed among 14 sections and numerous unranked groups. Here, we provide an updated, comprehensive classification of the genus, based on data from phylogeny, morphology, chromosome counts, and ploidy, and based on modern principles of monophyly. The revision is presented as an annotated global checklist of accepted species of Viola, an updated multigene phylogenetic network and an ITS phylogeny with denser taxon sampling, a brief summary of the taxonomic changes from Becker's classification and their justification, a morphological binary key to the accepted subgenera, sections and subsections, and an account of each infrageneric subdivision with justifications for delimitation and rank including a description, a list of apomorphies, molecular phylogenies where possible or relevant, a distribution map, and a list of included species. We distribute the 664 species accepted by us into 2 subgenera, 31 sections, and 20 subsections. We erect one new subgenus of Viola (subg. Neoandinium, a replacement name for the illegitimate subg. Andinium), six new sections (sect. Abyssinium, sect. Himalayum, sect. Melvio, sect. Nematocaulon, sect. Spathulidium, sect. Xanthidium), and seven new subsections (subsect. Australasiaticae, subsect. Bulbosae, subsect. Clausenianae, subsect. Cleistogamae, subsect. Dispares, subsect. Formosanae, subsect. Pseudorupestres). Evolution within the genus is discussed in light of biogeography, the fossil record, morphology, and particular traits. Viola is among very few temperate and widespread genera that originated in South America. The biggest identified knowledge gaps for Viola concern the South American taxa, for which basic knowledge from phylogeny, chromosome counts, and fossil data is virtually absent. Viola has also never been subject to comprehensive anatomical study. Studies into seed anatomy and morphology are required to understand the fossil record of the genus.

Vimentin and Ki-67 immunolabeling in canine gastric carcinomas and their prognostic value.

This study evaluated the expression of vimentin and Ki-67 proliferative index (PI) by immunohistochemistry in 30 canine gastric carcinomas (GCs) and a possible association with clinical and pathological features and patient's survival time. Vimentin immunoreactivity was assessed in neoplastic cells (in primary lesions, emboli, and metastases) and tumor-associated stroma (TAS) of canine GCs. Ki-67 PI was quantified in the neoplastic epithelial component. Vimentin immunolabeling in neoplastic cells was found in 30% of the primary lesions, in 82% of the neoplastic emboli, and in 50% of the metastases; in TAS, it was observed in all cases. A mean of 16% of the TAS was immunolabeled for vimentin. High vimentin immunolabeling in the TAS (>16%) was detected in 40% of cases. The average value of Ki-67 PI was 50%, and 80% of the lesions had Ki-67 PI above 20%. Vimentin immunolabeling in neoplastic cells was more frequent in less-differentiated carcinomas (diffuse [29%] and indeterminate types [75%]) than well-differentiated carcinomas (intestinal type [0%], P = .049). No significant differences were observed in vimentin immunolabeling in the TAS or Ki-67 PI according to histological diagnosis, depth of invasion, presence of neoplastic emboli or metastases. However, vimentin immunolabeling in the TAS was positively correlated with Ki-67 PI (r = .394, P = .031). Furthermore, a moderate negative correlation was observed between Ki-67 PI and survival time (r = -0.540). Our results suggest that vimentin and Ki-67 PI have potential for providing prognostic information in cases of canine GCs.

Perinatal derivatives: How to best characterize their multimodal functions in vitro. Part C: Inflammation, angiogenesis, and wound healing.

Perinatal derivatives (PnD) are birth-associated tissues, such as placenta, umbilical cord, amniotic and chorionic membrane, and thereof-derived cells as well as secretomes. PnD play an increasing therapeutic role with beneficial effects on the treatment of various diseases. The aim of this review is to elucidate the modes of action of non-hematopoietic PnD on inflammation, angiogenesis and wound healing. We describe the source and type of PnD with a special focus on their effects on inflammation and immune response, on vascular function as well as on cutaneous and oral wound healing, which is a complex process that comprises hemostasis, inflammation, proliferation (including epithelialization, angiogenesis), and remodeling. We further evaluate the different in vitro assays currently used for assessing selected functional and therapeutic PnD properties. This review is a joint effort from the COST SPRINT Action (CA17116) with the intention to promote PnD into the clinics. It is part of a quadrinomial series on functional assays for validation of PnD, spanning biological functions, such as immunomodulation, anti-microbial/anti-cancer activities, anti-inflammation, wound healing, angiogenesis, and regeneration.

E-cadherin Expression in Canine Gastric Carcinomas: Association with Clinicopathological Parameters.

E-cadherin (E-cad) is a cell-adhesion molecule known for its tumor-invasion suppressor function. E-cad expression was examined immunohistochemically in a series of canine tissue samples, including normal gastric mucosa (NGM; n = 3), gastric carcinomas (GC; n = 33), adjacent non-neoplastic mucosa (NNM; n = 32), neoplastic emboli (n = 16) and metastatic lesions (n = 9). The relationship between E-cad expression and clinicopathological features were investigated. In NGM, epithelial cells showed strong latero-lateral membranous expression of E-cad, and this pattern was considered normal. The membranous staining was preserved in all specimens of NNM (100%), whereas abnormal E-cad expression was found in 87.9% of the GCs. A marked difference in E-cad expression was observed between normal and malignant tissues (p < 0.0002). Abnormal E-cad expression was significantly more frequent in poorly/undifferentiated carcinomas (96%) and diffuse (95%) and indeterminate carcinomas (100%) than in well-differentiated/intestinal ones (62.5%; p = 0.0115 and p = 0.0392, respectively). There was significant association between abnormal E-cad expression and the depth of invasion (p = 0.0117), and the presence neoplastic emboli (p = 0.0194). No statistically significant differences in E-cad expression were observed concerning tumor location, histological type according to WHO classification, and presence of metastatic lesions. Therefore, deregulation of E-cad expression may play a role in canine gastric carcinogenesis and in tumor progression; moreover, it might be a prognostic tool for canine gastric cancer.

Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Using the Khorana risk score to predict venous thromboembolism and overall survival in a cohort of Hispanic patients with solid malignancies.

Background: The Khorana risk score (KRS) for prognosis of venous thromboembolism (VTE) has been rarely explored in Hispanic populations. Objective: To determine the value of the KRS for prediction of VTE and overall survival (OS) among Hispanic individuals with cancer. Methods: We retrospectively evaluated all outpatients with newly diagnosed solid tumours receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. The 6-month cumulative VTE incidence according to the KRS categories was estimated using the Fine & Gray competing risk model. A Kaplan-Meier analysis was used to compare OS among KRS categories. The Cox regression analysis was performed to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI). The receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff value to predict VTE during follow-up. Results: A total of 708 patients were included in the analysis. After a median follow-up of 8.13 months, the cumulative incidence of VTE at 6 months was 1.56% (95% CI: 0.83%-6.82%), 4.83% (95% CI: 2.81%-7.66%) and 8.84% (95% CI: 4.30%-15.42%) for low-, intermediate- and high-risk Khorana score categories, respectively (Gray's p value: 0.0178). The optimal cutoff for the KRS to predict VTE was 2 (area under the ROC curve: 0.65; 95% CI: 0.55-0.756). The KRS was independently associated with overall mortality (HR: 1.83; 95% CI: 1.46-2.29; p < 0.001, for the comparison of 'high-risk' and 'low-risk' KRS). Conclusions: The KRS is a valid tool to predict VTE and mortality in a cohort of Hispanic outpatients with newly diagnosed solid tumours.

Effects of Oral Zafirlukast, Sildenafil, or Pirfenidone on the Formation of Postsurgical Intra-Abdominal Adhesions in an Experimental Rat Model.

INTRODUCTION: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with sildenafil, zafirlukast, and pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral zafirlukast, sildenafil, or pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. METHODS: Four groups, each of 10 male Wistar rats weighing 250-300 g, were used. A midline laparotomy was used to excise an area of 1.5 × 1.5 cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of zafirlukast (1.25 mg/kg, group B), sildenafil (15 mg/kg, group C), or pirfenidone (500 mg/kg, group D) were given every day for 8 days. The control group, A, received no treatment. At day 9, animals were reoperated. The implant was resected after ethically approved euthanasia, and specimens were fixed in 10% formaldehyde for histopathology. RESULTS: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (p = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (p = 0.04). Adhesions in group C had less fibrovascular density (p = 0.03) with decreased serosal injuries (p = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (p < 0.01) and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than group B or C (p < 0.01). CONCLUSIONS: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral pirfenidone offered the best performance and could be recommended for human use.

Perinatal mesenchymal stromal cells of the human decidua restore continence in rats with stress urinary incontinence induced by simulated birth trauma and regulate senescence of fibroblasts from women with stress urinary incontinence.

Stress urinary incontinence (SUI) is a condition that causes the involuntary loss of urine when making small efforts, which seriously affects daily life of people who suffer from it. Women are more affected by this form of incontinence than men, since parity is the main risk factor. Weakening of the pelvic floor tissues is the cause of SUI, although a complete understanding of the cellular and molecular mechanisms of the pathology is still lacking. Reconstructive surgery to strengthen tissue in SUI patients is often associated with complications and/or is ineffective. Mesenchymal stromal cells from the maternal side of the placenta, i.e. the decidua, are proposed here as a therapeutic alternative based on the regenerative potential of mesenchymal cells. The animal model of SUI due to vaginal distention simulating labor has been used, and decidual mesenchymal stromal cell (DMSC) transplantation was effective in preventing a drop in pressure at the leak point in treated animals. Histological analysis of the urethras from DMSC-treated animals after VD showed recovery of the muscle fiber integrity, low or no extracellular matrix (ECM) infiltration and larger elastic fibers near the external urethral sphincter, compared to control animals. Cells isolated from the suburethral connective tissue of SUI patients were characterized as myofibroblasts, based on the expression of several specific genes and proteins, and were shown to achieve premature replicative senescence. Co-culture of SUI myofibroblasts with DMSC via transwell revealed a paracrine interaction between the cells through signals that mediated DMSC migration, SUI myofibroblast proliferation, and modulation of the proinflammatory and ECM-degrading milieu that is characteristic of senescence. In conclusion, DMSC could be an alternative therapeutic option for SUI by counteracting the effects of senescence in damaged pelvic tissue.

Differences in Postoperative Pain, Nausea, and Vomiting After Elective Laparoscopic Cholecystectomy in Premenopausal and Postmenopausal Mexican Women.

BACKGROUND: Postoperative symptoms and pain after laparoscopic cholecystectomy (LC) are common in women. However, there is no evidence of differences in incidence and severity among different age groups. We evaluated whether adverse postoperative symptoms were more common in younger than in older women after LC. METHODS: One hundred and fifty premenopausal (mean age 37.6 ± 3.6 y) and 145 postmenopausal women (59 ± 5.2 y) were included in this retrospective cohort study. Clinical and anthropometric parameters were analyzed. Study endpoints were the incidences of postoperative nausea and vomiting (PONV) and pain, and the additional analgesics and antiemetics needed after surgery. RESULTS: Body mass index was normal in 42.7% of patients in the younger group and 64.8% in the older group (P < 0.001). Reported pain was more frequent and intense in the younger group throughout the study period (P < 0.01). Additional narcotics were required in 18% of premenopausal versus 7.6% of postmenopausal women (P = 0.001), and the doses used to reduce pain were higher for premenopausal women (P = 0.02). PONV was more frequent in the younger group at 1 and 6 h after surgery (P < 0.005). Rescue antiemetics were required in 29 premenopausal and 13 postmenopausal women (P = 0.01). Hospital stay was shorter for the older patients (P = 0.01). Minor morbidity was observed in both groups (0.7% and 2.1%). There was no mortality. CONCLUSIONS: Early PONV and pain after LC were more frequent in premenopausal women, who also required more rescue analgesic and antiemetic medication.

Immunoexpression of Trefoil Factor 1 in Non-Neoplastic and Neoplastic Canine Gastric Tissues.

TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in >75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p < 0.05). No significant differences in the expression of TFF1 were found in GCs, according to age, sex, histological type based on World Health Organization (WHO) and Lauren classification, tumor location, depth of tumor invasion, presence of neoplastic emboli or metastatic lesions. The median survival time of GC patients with preserved and reduced TFF1 immunoexpression were 30 and 12 days, respectively. Kaplan-Meier analysis revealed no significant survival differences between the two groups (p > 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma.

Cell therapy for factor V deficiency: An approach based on human decidua mesenchymal stem cells.

Deficiency of factor V is a congenital autosomal recessive coagulopathy associated with mutations in the F5 gene that results in mild-to-severe bleeding episodes. Factor V is a component of the prothrombinase complex responsible for accelerating conversion of prothrombin to thrombin. At the present time there are no therapeutic factor V concentrates available. This study was designed to lay the preliminary foundations for future cell-based therapy for patients with severe factor V deficiency. The study showed that hepatospheres, which produce coagulation factors VIII, IX, and V, synthetize and store intracellular glycogen and express albumin levels up to 8 times higher than those of undifferentiated cells. Factor IX and factor V gene expression increased significantly in hepatospheres as compared to undifferentiated cells, whereas factor VIII gene expression remained constant. The factor V protein was detected in the hepatospheres´ secretome. Considering the enormous potential of mesenchymal stem cells as therapeutic agents, this study proposes a highly reproducible method to induce differentiation of mesenchymal stem cells from human placenta to factor V-producing hepatospheres. This strategy constitutes a preliminary step towards a curative treatment of factor V deficiency through advanced therapies such as cell therapy.

Evaluation of the effect of triclosan coated sutures in the prevention of surgical site infections in a Spanish hospital setting: A prospective, observational study.

BACKGROUND: Surgical site infections (SSIs) are one of the most frequently reported types of hospital-acquired infection and are associated with substantial clinical and economic burden. AIM: To assess the incidence of SSIs and analyze contributing risk factors in a real-world Spanish hospital setting before and after the implementation of triclosan-coated sutures (TCS). METHODS: A prospective, observational study was conducted at Hospital Clínico Universitario de Santiago de Compostela, Spain. Enrolled patients underwent surgery in the following specialties: general surgery, urology, neurosurgery, gynaecology, and traumatology. The primary outcome of the study was SSI incidence, assessed at a 30-day follow-up. Secondary outcomes were length of hospital stay, and readmission, reintervention, and mortality rates, also at 30 days. FINDINGS: 5,081 patients were included in the study, of which 2,591 were treated using non-coated sutures (NCS) and 2,490 using TCS. After adjusting for potential confounders, TCS significantly reduced SSI rate by 36%, compared with NCS (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.48-0.85; P<0.003). When stratified by wound classification, a statistically significant reduction in SSI incidence, in favour of TCS use, was observed for Class IV (dirty) wounds (35.6% versus 22.7% for NCS and TCS, respectively; OR: 0.53; 95% CI: 0.31-0.90). CONCLUSION: The use of TCS reduced SSI risk when compared with NCS. This reduction was significant for Class IV wounds, providing evidence that supports the use of TCS for this type of wound.