Expression of IL-17RA in Innate Cells of Patients with Common Variable Immunodeficiency (CVID) and its Clinical Implications.

Summary: Background. Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by B-cell dysfunction and immunoglobulin production deficiency. Dysregulation of interleukin-17 (IL-17) and its receptor IL-17RA have been reported in various immune disorders. This study aimed to investigate the expression of IL-17RA in innate immune cells of CVID patients and its correlation with clinical manifestations. Methods. A cross-sectional study included 22 CVID patients and 14 age- and sex-matched healthy controls. IL-17RA expression was assessed in various immune cell subsets using flow cytometry. Demographic and clinical data were collected, and statistical analysis was performed. Results. CVID patients had elevated IL-17RA expression in neutrophils, non-classical monocytes, and dendritic cells compared to healthy controls. Patients with a history of intestinal microbial colonization, particularly with Campylobacter jejuni and Giardia intestinalis, showed significantly higher IL-17RA expression in innate cells. Elevated IL-17RA expression in monocytes and dendritic cells also correlated with higher fecal calprotectin levels in CVID patients, regardless of microbial colonization. Conclusions. The study suggests that despite previous reports of reduced circulating Th17 cells and IL-17 levels in CVID patients, IL-17RA expression in innate cells may be elevated, potentially indicating altered IL-17 signaling. This heightened IL-17RA expression could contribute to a persistent pro-inflammatory state, possibly due to microbial translocation or other inflammatory factors. The association of IL-17RA expression with gastrointestinal microbial colonization and its correlation with fecal calprotectin underscores the complexity of IL-17RA's role in CVID pathophysiology. Further research in larger cohorts could elucidate the implications of IL-17RA expression in both infectious and non-infectious inflammatory aspects of CVID.

Sensitization to genuine markers of timothy grass pollen (Phleum pratense) in the North-Central region of Portugal.

Summary: Pollens are the main cause of respiratory allergies which prevalence is increasing. The most important cause of pollinosis in Europe and especially in the Mediterranean countries as Portugal is Poaceae family pollen. Timothy grass (Phleum pratense) is one of the most common pollen sources, and one of the best characterized allergenic grasses. The major allergens Phl p1 and Phl p5 are considered markers of genuine grass pollen sensitization. A characterization of Phl p1 and Phl p5 sensitization in the North-Central region of Portugal was made in children and adults. Phl p1 sensitization was the most frequent.

Innovative application of brackish groundwater without the addition of nutrients in the cultivation of Spirulina and Chlorella for carbohydrate and lipid production.

Brackish groundwater is promising for the cultivation of economically important microalgae; however, its effects have been evaluated only after nutrient supplementation. In this study, 100% brackish groundwater was evaluated as a culture medium for Spirulina sp. (BGWS) and Chlorella fusca (BGWC). In addition, the effects of supplementation with 25% of the nutrients from Zarrouk (BGWS25) and BG-11 (BGWC25) culture media were evaluated. BGWS and BGWC increased the concentration (68.1% w w-1) and productivity of carbohydrate (35.3 mg L-1 d-1) in Spirulina sp. and increased the concentration (56.4% w w-1) and productivity (13.5 mg L-1 d-1) of lipids in C. fusca biomass, when compared to that in the respective controls. The use of brackish groundwater as the sole culture medium is an innovative alternative for the economic production of biomass rich in carbohydrates and lipids. This has potential applications for biofuel production.

Spirulina sp. LEB 18 cultivation in seawater and reduced nutrients: Bioprocess strategy for increasing carbohydrates in biomass.

This study aimed to evaluate the growth and production of biomolecules by Spirulina sp. LEB 18 cultivated in seawater. The seawater was used without nutrient addition (SW0) and supplemented with 100% (SW100), 50% (SW50), and 25% (SW25) nitrogen, phosphorus, iron, and EDTA concentrations that make up the Zarrouk culture medium. When grown in SW0, Spirulina sp. LEB 18 showed maximum biomass concentration (2.17 g L-1) on the 11th d of cultivation and an increase in the carbohydrate content and productivity by 203% and 52%, respectively, when compared to the control culture. This cultivation strategy demonstrated the feasibility of using seawater as an alternative to freshwater in cultures as well as reduced nutritional requirements for biomass and carbohydrate production.

Factores predictivos de recidiva bioquímica temprana, intermedia y tardía tras prostatectomía radical mínimamente invasiva en una cohorte unicéntrica con seguimiento medio de 8 años / Predictors of early, intermediate and late biochemical recurrence after minimally invasive radical prostatectomy in a single-centre cohort with a mean follow-up of 8 years

Objetivo: Determinar factores predictivos de recidiva bioquímica (RB) temprana, intermedia y tardía después de prostatectomía radical mínimamente invasiva en pacientes con cáncer de próstata localizado. Material y métodos: Se incluyeron 6.195 pacientes con cáncer de próstata cT1-3N0M0 intervenidos mediante prostatectomía radical laparoscópica (PRL) y robótica en nuestra institución entre 2000 y 2016. Ninguno recibió tratamiento adyuvante. La RB se definió como PSA ≥ 0,2 ng/dl. El tiempo hasta RB se dividió en terciles para identificar variables asociadas con recidiva temprana (< 12 meses), intermedia (12-36 meses) y tardía (> 36 meses). Se utilizaron modelos de regresión logística para determinar los factores de riesgo asociados en cada intervalo. Resultados: Se identificaron 1.148 (18,3%) pacientes con RB. La mediana de tiempo hasta la RB fue de 24 meses (RIQ: 0,98-53,18). El análisis multivariable mostró que el PSA preoperatorio, la invasión ganglionar, los márgenes positivos y la PRL se asociaron con recidiva precoz (todos p ≤ 0,029). La cirugía laparoscópica fue el único predictor de recidiva intermedia (p = 0,001). Los predictores de recidiva tardía incluyeron un score de Gleason patológico ≥7, estadio ≥pT3, márgenes positivos y PRL (todos con p ≤ 0,02). Conclusiones: Los pacientes con cáncer de próstata de alto riesgo pueden desarrollar recurrencia tardía y precisar un seguimiento a largo plazo. La identificación de pacientes con mayor PSA e invasión ganglionar tiene un importante papel predictivo en el primer año tras la cirugía. La asociación entre PRL y RB merece una evaluación adicional

Objective: To determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localised prostate cancer (PC). Material and methods: We included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2 ng/dL. The time to BR is divided into terciles to identify the variables associated with early (< 12 months), intermediate (12-36 months) and late (> 36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. Results: We identified 1148 (18.3%) patients with BR. The mdian time to BR was 24 months (IQR, 0.98-53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (P≤ .029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (P = .001). The predictors of late recurrence included a pathological Gleason score ≥ 7, stage ≥ pT3, positive margins and RLP (P≤.02 for all). Conclusions: The patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment

Predictors of early, intermediate and late biochemical recurrence after minimally invasive radical prostatectomy in a single-centre cohort with a mean follow-up of 8 years. / Factores predictivos de recidiva bioquímica temprana, intermedia y tardía tras prostatectomía radical mínimamente invasiva en una cohorte unicéntrica con seguimiento medio de 8 años.

OBJECTIVE: To determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localised prostate cancer (PC). MATERIAL AND METHODS: We included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2 ng/dL. The time to BR is divided into terciles to identify the variables associated with early (<12 months), intermediate (12-36 months) and late (>36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. RESULTS: We identified 1148 (18.3%) patients with BR. The median time to BR was 24 months (IQR, 0.98-53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (P≤.029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (P=.001). The predictors of late recurrence included a pathological Gleason score ≥7, stage ≥pT3, positive margins and RLP (P≤.02 for all). CONCLUSIONS: The patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment.

Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis.

Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects of decreasing the risk of fractures and an indication of reducing the progression of osteoarthritis (OA). This study aimed to investigate the effects of SrRan as either a prophylactic or a treatment drug, using an OA rat model to assess pain behavior. A monoiodoacetate (MIA)-induced knee joint OA model in Wistar rats was used. Thirty Wistar rats (both sexes, 60 days old) were distributed in five groups of 6 rats each: the control group, that received no intervention; a prophylactic group, that received oral administration of 25 mg·kg-1·day-1 of SrRan for 28 days before induction of OA; a group treated with 25 mg·kg-1·day-1 of SrRan for 28 days after OA induction; a group treated with 50 mg·kg-1·day-1 during 28 days after OA induction; and a group that received oral saline for 28 days after induction. The assessment of pain behavior was performed considering articular incapacitation (weight-bearing test), mechanical hyperalgesia (Randall Selitto test) and motor activity (rotarod test), on days 0, 7, 14, 21, and 28. This experiment did not yield a significant difference when comparing the group that received SrRan prophylactically with the groups treated with 25 or 50 mg·kg-1·day-1 and the group that received oral saline. Thus, SrRan did not provide analgesia in either treated rats or as a prophylactic drug with the tested doses. Higher doses should be tested further to achieve possible significant results.

Transporters affecting biochemical test results: Creatinine-drug interactions.

Creatinine is eliminated by the kidneys through a combination of glomerular filtration and active transport. Drug-induced increases in serum creatinine (SCr) and/or reduced creatinine renal clearance are used as a marker for acute kidney injury. However, inhibition of active transport of creatinine can result in reversible and, therefore, benign increases in SCr levels. Herein, the transporters involved in creatinine clearance are discussed, in addition to limitations of using creatinine as a biomarker for kidney damage.

Prevalence and associated factors for asthma in Brazilian and Japanese schoolchildren living in the city of São Paulo, Brazil.

OBJECTIVES: Ethnic background interferes on the prevalence of asthma among schoolchildren (4 to 9 years old, SC) born and living in São Paulo, Brazil. METHODS: International Study of Asthma and Allergy in Childhood (ISAAC)'s written standard and complementary questionnaires were applied to SC (similar socioeconomic status) living in the city of São Paulo: no-Japanese Brazilian (NJB, N = 306) and Japanese Brazilian (third generation, born in Brazil, from Japanese families with no miscegenation, JB, N = 258). RESULTS: The prevalence of current asthma was significantly higher among NJB in comparison to JB (22.2% vs 14.7%, respectively). To have rhinitis and to exercise less than once/week were risk factors for both groups of children. CONCLUSION: Although both groups were apparently exposed to the same environment, other cultural differences do not allow us to conclude about the ethnic component having greater influence than the environment in the development of asthma in these individuals.

Molecular and antigenic characterization of bovine Coronavirus circulating in Argentinean cattle during 1994-2010.

Bovine coronavirus (BCoV) is an important viral pathogen associated with neonatal calf diarrhea. Our aim was to investigate the incidence of BCoV in diarrhea outbreaks in beef and dairy herds from Argentina during 1994-2010. A total of 5.365 fecal samples from diarrheic calves were screened for BCoV diagnosis by ELISA. The virus was detected in 1.71% (92/5365) of the samples corresponding to 5.95% (63/1058) of the diarrhea cases in 239 beef and 324 dairy farms. The detection rate of BCoV was significantly higher in dairy than in beef herds: 12.13% (29/239) vs. 4.32% (14/324) respectively. Phylogenetic analysis of the hypervariable S1 region of seven representative samples (from different husbandry systems, farm locations and years of sampling) indicated that BCoV strains circulating in Argentinean beef and dairy herds formed a cluster distinct from other geographical regions. Interestingly, Argentinean strains are distantly related (at both the nucleotide and amino acid levels) with the Mebus historic reference BCoV strain included in the vaccines currently available in Argentina. However, Mebus-induced antibodies were capable of neutralizing the BCoV Arg95, a field strain adapted to grow in vitro, and vice versa, indicating that both strains belong to the same CoV serotype reported in cattle. This work represents the first large survey describing BCoV circulation in Argentinean cattle.

Prolonged saltatory fetal heart rate pattern leading to newborn metabolic acidosis.

PURPOSE: The saltatory pattern, characterized by wide and rapid oscillations of the fetal heart rate (FHR), remains a controversial entity. The authors sought to evaluate whether it could be associated with an adverse fetal outcome. MATERIAL AND METHODS: The authors report a case series of four saltatory patterns occurring in the last 30 minutes before birth in association with cord artery metabolic acidosis, obtained from three large databases of internally acquired FHR tracings. The distinctive characteristics of this pattern were evaluated with the aid of a computer system. RESULTS: All cases were recorded in uneventful pregnancies, with normal birthweight singletons, born vaginally at term. The saltatory pattern lasted between 23 and 44 minutes, exhibited a mean oscillatory amplitude of 45.9 to 80.0 beats per minute (bpm) and a frequency between four and eight cycles per minute. CONCLUSIONS: A saltatory pattern exceeding 20 minutes can be associated with the occurrence of fetal metabolic acidosis.

Effects of gamma radiation on raspberries: safety and quality issues.

There is an ever-increasing global demand from consumers for high-quality foods with major emphasis placed on quality and safety attributes. One of the main demands that consumers display is for minimally processed, high-nutrition/low-energy natural foods with no or minimal chemical preservatives. The nutritional value of raspberry fruit is widely recognized. In particular, red raspberries are known to demonstrate a strong antioxidant capacity that might prove beneficial to human health by preventing free radical-induced oxidative stress. However, food products that are consumed raw, are increasingly being recognized as important vehicles for transmission of human pathogens. Food irradiation is one of the few technologies that address both food quality and safety by virtue of its ability to control spoilage and foodborne pathogenic microorganisms without significantly affecting sensory or other organoleptic attributes of the food. Food irradiation is well established as a physical, nonthermal treatment (cold pasteurization) that processes foods at or nearly at ambient temperature in the final packaging, reducing the possibility of cross contamination until the food is actually used by the consumer. The aim of this study was to evaluate effects of gamma radiation on raspberries in order to assess consequences of irradiation. Freshly packed raspberries (Rubus idaeus L.) were irradiated in a (60)Co source at several doses (0.5, 1, or 1.5 kGy). Bioburden, total phenolic content, antioxidant activity, physicochemical properties such as texture, color, pH, soluble solids content, and acidity, and sensorial parameters were assessed before and after irradiation and during storage time up to 14 d at 4°C. Characterization of raspberries microbiota showed an average bioburden value of 10(4) colony-forming units (CFU)/g and a diverse microbial population predominantly composed of two morphological types (gram-negative, oxidase-negative rods, 35%, and filamentous fungi, 41%). The inactivation studies on the raspberries mesophilic population indicated a one log reduction of microbial load (95% inactivation efficiency for 1.5 kGy), in the surviving population mainly constituted by filamentous fungi (79-98%). The total phenolic content of raspberries indicated an increase with radiation doses and a decrease with storage time. The same trend was found for raspberries' antioxidant capacity with storage time. Regarding raspberries physicochemical properties, irradiation induced a significant decrease in firmness compared with nonirradiated fruit. However, nonirradiated and irradiated fruit presented similar physicochemical and sensory properties during storage time. Further studies are needed to elucidate the benefits of irradiation as a raspberries treatment process.

CCR5 mediates pro-osteoclastic and osteoclastogenic leukocyte chemoattraction.

Periodontal disease (PD) progression involves the selective leukocyte infiltration into periodontium, supposedly mediated by the chemokine/chemokine receptor system. In this study, we investigated the role of chemokine receptor CCR5 in the immunoregulation of experimental PD in C57BL/6 (WT) and CCR5KO mice. Aggregatibacter actinomycetem comitans infection triggered the chemoattraction of distinct CCR5+ leukocyte subpopulations (determined by flow cytometry): CCR5+F4/80+ leukocytes, which co-express CD14 , CCR2, TNF-α, and IL-1ß, indicative of activated macrophages; and CCR5+CD4+ cells, which co-express CXCR3, IFN-γ, and RANKL, indicative of Th1 lymphocytes, therefore comprising pro-osteoclastic and osteoclastogenic cell subsets, respectively. CCR5KO mice presented a lower PD severity (lower inflammation and alveolar bone loss) when compared with the WT strain, since the migration of F4/80+, TNF-α+, CD4+, and RANKL+ cells specifically decreased due to the lack of CCR5. Also, ELISA analysis demonstrated that the production of TNF-α, IL-1ß, IL-6, IFN-γ, and RANKL in periodontal tissues was significantly decreased in the CCR5KO strain. The periodontal bacterial load and antimicrobial patterns were unaltered in CCR5KO mice. Our results demonstrate that the chemokine receptor is involved in the migration of distinct leukocyte subpopulations throughout experimental PD, being a potential target for therapeutic intervention in PD.

Effect of temozolomide on the U-118 glioma cell line.

Glioblastomas (GBM) are the most lethal subtype of astrocytomas, with a mean patient survival rate of 12 months after diagnosis. The gold standard treatment of GBM, which includes surgery followed by the combination of radiotherapy and chemotherapy with temozolomide (TMZ), increases the survival rate to 14.6 months. The success of TMZ appears to be limited by the occurrence of chemoresistance that allows glioma cells to escape from death signaling pathways. However, the mechanism of TMZ action is yet to be clarified although some controversial results have been reported. Therefore, our aim was to evaluate the occurrence of apoptosis and autophagy in glioma cells treated with TMZ and to correlate TMZ action with the survival pathways Pi3K/Akt and ERK1/2 MAP kinase. Cell proliferation was evaluated by incorporation of bromodeoxyuridine. Apoptosis was studied by flow cytometry as well as by fluorescence confocal microscopy in order to evaluate the sub G0/G1 percentage of cells and chromatin condensation. The expression of the autophagy-associated protein, LC3, as well as Akt and ERK1/2 was performed by Western blotting. In TMZ-treated GBM cells the expression of LC3, the autophagy-associated protein was increased and only a reduced percentage of cells underwent apoptosis. In addition, we showed that the phosphorylation status of Pi3K/Akt and ERK1/2 MAP kinase was maintained during the treatment with TMZ, suggesting that glioma cells escape from TMZ-induced cell death due to these signaling pathways. The chemoresistance of U-118 cells to TMZ was partially eradicated when cells were simultaneously treated with specific inhibitors of Pi3K/Akt and ERK1/2 MAP kinase signaling pathways and TMZ. Therefore, we hypothesized that in order to induce glioma cell death it is essential to evaluate the activation of the survival pathways and establish a combined therapy using TMZ and inhibitors of those signaling pathways.

Prevalence of symptoms of asthma, rhinitis, and atopic eczema among adolescents living in urban and rural areas in different regions of Brazil.

BACKGROUND: In Brazil, studies evaluating the prevalence of asthma and allergic diseases among children living in rural area compared to urban area are rare. Some authors identified as risk factors for higher prevalence of current wheezing to have a family history of asthma, to have contact with pets, and being student in an urban school. The International Study of Asthma and Allergies in Childhood (ISAAC) phase 3 has shown higher prevalence of wheezing, nasal symptoms and cutaneous rash in the last 12 months in centers from Northern (N) and Northeastern (NE) regions of Brazil. OBJECTIVE: To evaluate if adolescents with similar genetic background, living in a rural area are protected against the development of symptoms of asthma, rhinitis, and atopic eczema when compared to those living in an urban area in the same region of the country. SUBJECTS AND METHOD: Adolescents (13-14 year-old) living in Caruaru (Pernambuco) and in Santa Maria (Rio Grande do Sul) were enrolled in this study (2002-2003). The adolescents filled in the ISAAC written questionnaire (WQ), previously translated and validated to the Brazilian culture (30-32). Data obtained were transcribed manually into a database (Epi-Info) supplied by ISAAC's coordinators and were statistically analyzed by the SSPS-12 software. RESULTS: The prevalence of asthma related symptoms were higher among those adolescents living in the urban centers in comparison to the rural ones. These differences were significant for wheezy ever, wheezy in the last 12 months, asthma ever, and wheezy with exercise in Caruaru and for wheezy ever and asthma ever, in Santa Maria. Comparing urban areas, the prevalence of asthma related symptoms in Caruaru was higher than in Santa Maria, except for wheezy ever and wheezy with exercise. The opposite was observed comparing rural areas: the prevalence of asthma (except for nocturnal cough) was higher in Santa Maria despite lesser severity of symptoms in this city.

Prevalence of symptoms of asthma, rhinitis, and atopic eczema in Brazilian adolescents related to exposure to gaseous air pollutants and socioeconomic status.

OBJECTIVES: To evaluate the relationship between exposure to gaseous air pollutants (ozone [O3], carbon monoxide [CO], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) socioeconomic status and the prevalence of symptoms of asthma, rhinitis and atopic eczema in adolescents. SUBJECTS AND METHODS: A sample of 16 209 adolescents from São Paulo West (SPW), São Paulo South (SPS), Santo André (SA), Curitiba (CR), and Porto Alegre (PoA) were enrolled. Data on air pollutants and socioeconomic status were compared to prevalence of symptoms with the Spearman correlation coefficient. RESULTS: Socioeconomic status was quite similar in all cities. The levels of O3 in SPW, SPS, and SA, and of CO in SA were higher than the acceptable ones. In relation to O3 and CO exposures, adolescents from SPW and SA had a significant risk of current wheezing, whereas living in SPW was associated with a high risk of rhinoconjunctivitis, eczema, and flexural eczema and living in CR to rhinitis. Exposure to NO2 was associated with a high risk of current wheezing in SPW and SA, and of severe asthma in SPW and PoA. Exposure to SO2 was associated with a high risk of current wheezing in SPW and SA, severe asthma in SPW and PoA, and nighttime cough, eczema, flexural eczema and severe eczema in SPW. Living in SPW, CR, or PoA was associated with a high risk of rhinitis, rhinoconjunctivitis, and severe rhinitis. CONCLUSIONS: Although we did not detect a characteristic pattern for all symptoms evaluated or a specific air pollutant, our data suggest a relationship between higher exposure to photochemical pollutants and high prevalence or risk of symptoms of asthma, rhinitis, and atopic eczema.