Expresión de PD-L1 en cáncer renal, características pronósticas y utilidad en la práctica clínica habitual / Expression of PD-L1 in renal cancer, prognostic features and clinical utility of its routine staining

Introducción La expresión de PD-L1 en el carcinoma de células renales (CCR) se asocia a tasas de sobrevida y características clínico-patológicas pronósticas peores. Sin embargo, estos parecen responder mejor ante nuevos agentes terapéuticos. Conocer el comportamiento del CCR según la presencia de PD-L1 puede tener implicancias en la consejería de los pacientes y el abordaje terapéutico. Objetivo Identificar la presencia de PD-L1 en las células tumorales renales y analizar su asociación con los factores pronósticos de los pacientes, la sobrevida global (SG) y la sobrevida cáncer-específica (SCE). Metodología Análisis retrospectivo a partir de muestras de tejido de CCR obtenidas entre 2018 y 2021. Estudio inmunohistoquímico con anticuerpo monoclonal de ratón anti PD-L1, clon 22C3. Se definió PD-L1 «positivo» como una puntuación de proporción tumoral ≥ 1%. Comparación de factores pronósticos según la presencia o ausencia de PD-L1, y análisis univariante para la SG y la SCE. Resultados Un 14% (n=11) de la muestra era PD-L1(+). La edad media era de 59 años. No hubo diferencias estadísticamente significativas entre el estatus de PD-L1 y el estadio TNM, el grado nuclear y el tipo histológico. Los pacientes PD-L1(+) tuvieron peor SG con un HR de 5,27 (IC: 1,1-23,7; p=0,03) y la SCE mostró una tendencia desfavorable para PD-L1(+) con un HR de 4,79 (IC: 0,79-28,95; p=0,08). Conclusión La prevalencia de PD-L1 en el CCR es considerable. En este estudio, PD-L1(+) se asoció con una SG y SCE desfavorables, lo que justifica incorporar su uso rutinario en el CCR (AU)

Introduction The expression of PD-L1 in renal cell carcinoma (RCC) is associated with worse survival and prognostic clinical-pathological features. However, they seem to respond better to new therapeutic agents. Knowing the behavior of RCC according to the presence of PD-L1 may have implications for medical counseling and therapeutic approaches. Objective To identify the presence of PD-L1 in renal tumor cells and analyze its association with patientś prognostic factors, overall survival (OS) and cancer-specific survival (CSS). Methodology Retrospective analysis of RCC tissue samples, obtained between 2018 and 2021. Immunohistochemistry analysis with mouse monoclonal Anti PD-L1, clone 22C3. Definition of PD-L1 “positive” as a Tumor Proportion Score ≥ 1%. Comparison of prognostic factors according to the presence or absence of PD-L1, and univariate analysis for OS and CSS. Results 14% (n=11) of the sample were PD-L1(+). Average age was 59 years. There were no statistically significant differences between PD-L1 status and TNM stages, nuclear grade and histology. PD-L1(+) had worse OS with a HR of 5.27 (CI: 1.1-23.7; p=0.03) and CSS showed a unfavorable tendency for PD-L1(+) with a HR of 4.79 (CI: 0.79-28.95; p=0.08). Conclusion The prevalence of PD-L1 in RCC is considerable. In this study PD-L1(+) was associated with unfavorable OS and CSS. It seems reasonable to incorporate its routine use in RCC (AU)

Expression of PD-L1 in renal cancer, prognostic features and clinical utility of its routine staining.

INTRODUCTION: The expression of PD-L1 in renal cell carcinoma (RCC) is associated with worse survival and prognostic clinical-pathological features. However, they seem to respond better to new therapeutic agents. Knowing the behavior of RCC according to the presence of PD-L1 has implications for medical counseling and therapeutic approaches. OBJECTIVE: To identify the presence of PD-L1 in renal tumor cells and analyze its association with patients' prognostic factors, overall survival (OS) and cancer-specific survival (CSS). METHODOLOGY: Retrospective analysis of RCC tissue samples, obtained between 2018 and 2021. Immunohistochemistry analysis with mouse monoclonal Anti PD-L1, clone 22C3. Definition of PD-L1 "positive" as a Tumor Proportion Score ≥1%. Comparison of prognostic factors according to the presence or absence of PD-L1, and univariate analysis for OS and CSS. RESULTS: 14% (n = 11) of the sample were PD-L1(+). Average age was 59 years. There were no statistically significant differences between PD-L1 status and TNM stages, nuclear grade and histology. PD-L1(+) had worse OS with a HR of 5.27 (CI: 1.1-23.7; P = .03) and CSS showed a unfavorable tendency for PD-L1(+) with a HR of 4.79 (CI: 0.79-28.95; P = .08). CONCLUSION: The prevalence of PD-L1 in RCC is considerable. In this study PD-L1(+) was associated with unfavorable OS and CSS. It seems reasonable to incorporate its routine use in RCC.

Optimizing the generation of polarization squeezed light in nonlinear optical fibers driven by femtosecond pulses.

Bright squeezed light can be generated in optical fibers utilizing the Kerr effect for ultrashort laser pulses. However, pulse propagation in a fiber is subject to nonconservative effects that deteriorate the squeezing. Here, we analyze two-mode polarization squeezing, which is SU(2)-invariant, robust against technical perturbations, and can be generated in a polarization-maintaining fiber. We perform a rigorous numerical optimization of the process and the pulse parameters using our advanced model of quantum pulse evolution in the fiber that includes various nonconservative effects and real fiber data. Numerical results are consistent with experimental results.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Enhancing axial localization with wavefront control.

Enhancing the ability to resolve axial details is crucial in three-dimensional optical imaging. We provide experimental evidence showcasing the ultimate precision achievable in axial localization using vortex beams. For Laguerre-Gauss (LG) beams, this remarkable limit can be attained with just a single intensity scan. This proof-of-principle demonstrates that microscopy techniques based on LG vortex beams can potentially benefit from the introduced quantum-inspired superresolution protocol.

Body composition of extreme performers in the US Marine Corps.

BACKGROUND: The creation of highly muscled and strong fighters is a recurring theme in human performance enhancement concepts. Physical readiness standards, intended to prevent obesity in the military, produce contradictory objectives, hounding large individuals to lose weight because of confusion between body size and body composition. Through selection, specialised training and policy exceptions the US Marine Corps has successfully developed a unique group of large (body mass index (BMI) >30 kg/m2) and strong individuals, the body bearers (BB) who carry coffins of Marines to their final resting place. METHODS: We examined the relationship between adiposity and body size from nine male BB (age 25.0±2.1, height: 1.84±0.04 (1.80-1.92) m, BMI: 33.0±2.1 (30-37) kg/m2). Body composition was assessed by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance (BIA) and tape measured abdominal circumference (AC)-based equations and from three-dimensional scanning (3DS). RESULTS: Measures were made of fat-free mass (FFM): 90.5±7.0 (82.0-106.7) kg, where FFM included total body water: 62.8±5.0 (55.8-71.8) L, representing 69±2 (67-73) % of FFM, along with calculated FFM index: 26.8±2.4 (24.4-32.9) kg/m2). DXA measures were made for bone mineral content 4.1±0.4 (3.5-4.9) kg, bone mineral density (BMD) 1.56±0.10 (1.37-1.76) g/cm2 and %BF 19.5±6.6 (9.0-27.8). Additional measures of percent body fat (%BF) were made by AC: 20.3±2.9 (15.2-24.6), BIA: 23.7±6.4 (9.8-29.2) and 3DS: 25.5±4.7 (18.9-32.2). AC %BF reasonably matched DXA %BF, with expected overprediction and underprediction at low and high DXA %BF. BIA %BF was affected by deviations from assumed FFM hydration (72%-73%). CONCLUSION: These men are classified as obese by BMI but carried massive amounts of muscle and bone on their large frames, while presenting a range of %BF irrelevant to strength performance. BMI did not predict obesity and adiposity had no association with muscle mass and strength performance.

The impacts of seasonal variation and climate on food utilization in a population of critically endangered cotton-top tamarins (Saguinus oedipus) in Colombia: A 22-year longitudinal study.

To examine how precipitation patterns and climate change impact feeding choices made by a population of critically endangered cotton-top tamarins (Saguinus oedipus), we examined 22 years of feeding data (1999-2020) from 21 groups collected at Parque Natural Regional Bosque Seco El Ceibal Mono Tití in Santa Catalina, Colombia. We describe the diet and examine the role of seasonal rainfall and annual variation in rainfall on diet. Rainfall is highly seasonal (mean annual rainfall 1562 mm [range 940-2680 mm]) with a dry, early rainy, and late rainy season in each year. Over 80 species of plants formed part of the fruit, nectar, and exudate components of the diet. Fruits, although available year-round, were more commonly available and consumed during the late rainy seasons (August-November). Exudates were consumed more frequently in the dry season (December-March) and invertebrate consumption was stable across the year. Nectar feeding from a single species (Combretum fruticosum) peaked in November. Rainfall varied over the years, with 13 years exceeding the 99% confidence intervals for mean rainfall. Ten of these extreme years (both drought and extremely wet) occurred in the last 11 years. Fruit consumption did not vary between extreme and average years, but cotton-top tamarins consumed more invertebrates and exudates in wet years. Presently, cotton-top tamarins appear to be able to cope with these extreme variations in rainfall due to their highly varied diet. However, the forests that these primates depend upon for survival are threatened by human exploitation making it critically important to maintain a generalist feeding strategy for survival as many fruiting trees that compose a large proportion of the diet are removed. As conservation efforts continue, plant species consumed by cotton-top tamarins provide useful data when selecting species for habitat restoration programs.

Murine colonization model by Campylobacter coli DSPV458.

AIMS: To generate a murine experimental model of colonization by Campylobacter coli DSPV458. METHODS AND RESULTS: Twelve adult Balb/cCmedc female mice were housed in a treated group (T-G) and a control group (C-G) for 4 weeks. Both experimental groups received antibiotics for 5 days during the first week. The T-G was administered with 6.68log10 CFU of C. coli DSPV458 by oesophageal gavage. Necropsies were performed weekly to evaluate translocation and intestinal colonization in the spleen and liver and in the ileum and cecum respectively. Samples were cultured to quantify intestinal microbiota members. Faeces were cultured weekly for a C. coli DSPV458 count. Campylobacter coli DSPV458 was isolated from all the inoculated mice. The recovered level of C. coli DSPV458 was, on average, 6.9 log10 CFUg-1 , 8.0 log10 CFUg-1 and 1.6 log10 CFUg-1 in faeces, cecum and ileum respectively. Colonization by C. coli DSPV458 does not alter the normal clinical and physiological status. CONCLUSIONS: Campylobacter coli DSPV458 does not have an invasive capacity, and the model is suitable for evaluating strategies to reduce intestinal loads. SIGNIFICANCE AND IMPACT OF STUDY: Farm animals have an important impact on thermotolerant Campylobacter transmission to humans. Extremely few colonization models by C. coli have been reported to date. In food-producing animals, infection is mild or absent and thermotolerant Campylobacter colonize the intestines of animals. Colonization models are specific models that do not cause infection as they do not generally result in diarrhoea or other signs of disease. Therefore, this model will allow to evaluate the evolution of colonization by thermotolerant Campylobacter and the alternative tools development to antibiotics that limit their colonization in food-producing animals.

Protective effect of Lactiplantibacillus plantarum LP5 in a murine model of colonisation by Campylobacter coli DSPV458.

Thermotolerant Campylobacter species are the leading cause of foodborne bacterial diarrheal disease worldwide. Campylobacter coli, abundant in pigs and pork products, have been identified as a source of human infection. In this study, we propose the use of Lactiplantibacillus plantarum LP5 as a probiotic to reduce colonisation of this intestinal pathogen in a murine colonisation model of C. coli DSPV458. Six-week-old adult female Balb/cCmedc mice were housed in groups: Control, Campy and Pro-Campy. Control and Pro-Campy groups received antibiotics for 5 days and the Campy group for 12 days. Pro-Campy group was inoculated for 7 days with 8.78 log10 cfu total of L. plantarum LP5 suspended in De Man, Rogosa and Sharpe broth. All groups were inoculated with 6.72 log10 cfu of C. coli DSPV458 suspended in brain heart infusion broth. L. plantarum LP5 was recovered only in the Pro- Campy group. C. coli DSPV458 was recovered at higher levels in the Control and Campy groups. The differences with the Pro-Campy group were significant. As regards faeces, Control and Campy groups reached 7.41 and 7.84 log10 cfu/g, respectively, and the Pro-Campy group only 4.62 log10 cfu/g. In the caecum, Control and Campy groups reached 8.01 and 9.26 log10cfu/g, respectively, and the Pro-Campy group only 4.51 log10 cfu/g. In the ileum, Control and Campy groups reached 3.43 and 3.26 log10 cfu/g, respectively, and the Pro-Campy group did not show detectable levels. The reduction of C. coli DSPV458 in the Pro-Campy group compared to the Control group in faeces, caecum and ileum was 99.55, 99.98 and 100%, respectively. Animals were maintained under normal health conditions, and haematological parameters were within the standard values for Balb/cCmedc. The incorporation of a probiotic generated a protective effect in the mice colonisation model. The protective effect would also apply to intestinal colonisation by indigenous enterobacteria. Therefore, the strategy used in this study is of great importance to understand the protection mechanisms in a murine model, as well as its application in food-producing animals.

Minor Ailment Service in Costa Rica: criteria to dispense a medicine or to refer to the physician / Servicio de Indicación Farmacéutica en Costa Rica: criterios asociados con dispensar un medicamento o derivar al médico

Introduction: Minor Ailment Service is a very common pharmaceutical service. The objective was to evaluate the criteria associated with the referral to physician or with dispensing medicines in those consultations in Costa Rica.Method: Observational descriptive cross-sectional multicenter exploratory study of: Minor Ailment Service consultations in 30 community pharmacies, and analyzed the factors associated with to refer to the physician or dispense medicines.Results: There were 1,538 consultations, of which medicines are dispensed in 92.3% of them (n=1,420), referred to the physician in 6.7% (n=103). In relation to the intervention of referring to the physician, the bivariate analysis showed a statistically significant association with them, highlighting the criteria suspected adverse drug reaction, medicines use currently for other health problem and duration of the health problem ≥7 days.Conclusions: The service is complex and shows that the pharmacist follows a series of criteria to make a decision –the referral to physician or dispensing medicines–. There are seven important criteria according to this study. However, the one that stands out is suspected adverse drug reaction, followed by medicines use currently for other health problems, duration of the health problem ≥7 days and pregnancy/lactation. (AU)

Introducción: La indicación farmacéutica es un servicio farmacéutico muy común. El objetivo fue evaluar criterios asociados con derivar al médico o dispensar.Método: Estudio exploratorio multicéntrico, descriptivo de las consultas de indicación farmacéutica en 30 farmacias comunitarias durante 8 semanas. Resultados: Hubo 1.538 consultas, de las cuales se dispensaron medicamentos en el 92,3% de ellas (n=1.420), remitidas al médico en el 6,7% (n=103). En relación con la intervención de referirse al médico, el análisis bivariado mostró una asociación estadísticamente significativa con ellos, destacando los criterios sospecha de reacción adversa a medicamentos, uso de medicamentos actualmente para otro problema de salud y duración del problema de salud ≥7 días.Conclusiones: El servicio es complejo y muestra que el farmacéutico sigue una serie de criterios para la derivación al médico o la dispensación. Hay siete criterios importantes según este estudio. Sin embargo, el que destaca es la sospecha de reacción adversa a medicamentos, seguido del uso de medicamentos actualmente para otros problemas de salud, la duración del problema de salud ≥7 días y el embarazo/lactancia. (AU)

In vitro screening and in vivo colonization pilot model of Lactobacillus plantarum LP5 and Campylobacter coli DSPV 458 in mice.

The objective of this work was to determine the antibacterial effect of Lactobacillus plantarum strains of pork origin against Campylobacter coli strains, and to conduct experimental colonization pilot models in mice for both microorganisms. Inhibition assays allowed evaluation and selection of L. plantarum LP5 as the strain with the highest antagonistic activity against C. coli and with the best potential to be used in in vivo study. Adult 6-week-old female Balb/cCmedc mice were lodged in two groups. The treated group was administered with 9.4 log10CFU/2 times/wk of L. plantarum LP5. L. plantarum LP5 was recovered from the feces and cecum of the inoculated mice. However, when bacteria stopped being administered, probiotic counts decreased. Experimental colonization with C. coli was carried out in five groups of mice. All animals were treated with antibiotics in their drinking water to weaken the indigenous microbiota and to allow colonization of C. coli. Four groups were administered once with different C. coli strains (DSPV458: 8.49 log10CFU; DSPV567: 8.09 log10CFU; DSPV570: 8.46 log10CFU; DSPV541: 8.86 log10CFU, respectively). After 8 h, mice inoculated with different C. coli strains were colonized because the pathogen was detected in their feces. L. plantarum LP5 tolerated the gastrointestinal conditions of murine model without generating adverse effects on the animals. C. coli DSPV458 colonized the mice without causing infection by lodging in their digestive tract, thus generating a reproducible colonization model. Both models combined could be used as protection murine models against pathogens to test alternative control tools to antibiotics.

Complete Genome Sequence of Halomonas venusta Type Strain DSM 4743, a Moderately Halophilic Marine Bacterium.

Here, we report the genome sequence of Halomonas venusta strain DSM 4743T, a moderately halophilic marine bacterium. This type species genome consists of a 4.3-Mb chromosome, with 3,777 protein-coding genes, 60 tRNA loci, and 6 complete rRNA operons, plus a 6.1-kb plasmid termed p4743-A.

Possible reservoirs of thermotolerant Campylobacter at the farm between rearing periods and after the use of enrofloxacin as a therapeutic treatment.

Campylobacteriosis is a zoonosis and the most frequent cause of food-borne bacterial enteritis in humans. C. jejuni and C. coli are the most common species implicated in campylobacteriosis. Broilers and their products are considered the most important food sources of human infections. The aim of the present study was to evaluate the presence of thermotolerant Campylobacter in different reservoirs at the farm, and the permanence of this pathogen during four consecutive rearing periods. The samples were taken from the same house farm in the downtime period and during the last week of broiler rearing, prior to their slaughter during four consecutive cycles. Different reservoirs as potential sources of Campylobacter were analysed. The prevalence of Campylobacter in vectors was 23% in A. diaperinus larvae, 20% in wild birds, 13% in A. diaperinus adults, and 9% in flies; as regards fomites, the prevalence was 50% in workers' boots, 27% in litter, and 21% in feed, while in broilers it was 80%. Campylobacter jejuni was the most detected species (51%) in the samples analysed. In addition, some Campylobacter genotypes persisted in the house farm throughout consecutive rearing periods, indicating that those strains remain during downtime periods. However, our study could not identify the Campylobacter sources in the downtime periods because all the samples were negative for Campylobacter isolation. In addition, a remarkable finding was the effect of the use of enrofloxacin (as a necessary clinical intervention for flock health) in cycle 3 on the Campylobacter population. No Campylobacter could be isolated after that clinic treatment. Afterwards, we found a greater proportion of C. coli isolates, and the genotypes of those isolates were different from the genotypes found in the previous rearing periods. In conclusion, the effect of the use of enrofloxacin during the rearing period changed the Campylobacter species proportion, and this finding is particularly interesting for further evaluation. Furthermore, more studies should be conducted with the aim of detecting the Campylobacter sources between rearing periods.

Molecular epidemiology of Campylobacter jejuni isolates from the broiler production chain: first report of MLST profiles in Argentina.

Campylobacter jejuni is an important foodborne pathogen with global distribution. We describe a genotyping study of a collection of C. jejuni (n=137) isolated from different broiler farms and from multiple sites along the processing line in a slaughterhouse in Argentina during 2011, 2012 and 2015. The isolates were genotyped using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Based on the PFGE results, the isolates were grouped into 26 pulsotypes. Subsequently, the isolates representing these 26 pulsotypes were chosen for MLST genotyping, which identified 16 different sequence types (STs) and 6 clonal complexes (CCs) (21, 45, 48, 353, 354, 446). Several of the STs (n=7) have not been previously reported in the PubMLST.org database. The most prevalent CCs were 21, 45 (both associated with human campylobacteriosis worldwide) and 353. This study showed high genetic diversity among C. jejuni in the broiler production environment in Argentina with novel MLST genotypes.

Effect of cadmium on the viability on monolayer cultures of synoviocytes, chondrocytes, and Hoffa: A preliminary study.

Osteoarthritis (OA) is the gradual loss of articular cartilage and involves several tissues, such as the synovial membrane, meniscus, ligaments, and adipose tissue known as Hoffa fat pad. There are largely unexplored factors that lead to OA development, such as the impact of exposure to heavy metals like cadmium (Cd) on the viability of cells in the knee joint tissue. The objective of this report was to identify the cell type with the highest susceptibility to Cd toxicity with respect to cell viability and death. Our findings showed that a concentration as low as 3 µM cadmium chloride for 12 h affects the viability of synovial cells, and a concentration of 10 µM affects Hoffa cells. Our results suggest that Cd can affect the viability of synovial and chondral cells primarily. In contrast, Hoffa cells were less susceptible, likely because Cd favors the production of pro-inflammatory cytokines before triggering their death as part of its damage mechanism at the articular level.