Thirty days of double-strain probiotic supplementation increases monocyte phagocytosis in marathon runners.

Marathon runners, subjected to intense training regimens and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: placebo (n 13) and probiotic (PRO) (n 14). Over 30 d, both groups received supplements - placebo sachets containing maltodextrin (5 g/d) and PRO sachets containing 1 × 1010 colony-forming unit Lactobacillus acidophilus and 1 × 1010 colony-forming unit Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels and monocyte immunophenotyping, were conducted at four different intervals: baseline (start of supplementation/30 d pre-marathon), 24 h-before (1 d pre-marathon), 1 h-after (1 h post-marathon) and 5 d-after (5 d post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after 30 d of supplementation. Upon lipopolysaccharide stimulation, both PRO and placebo groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5 d-after, while IL-1-ß, IL-8, IL-10, IL-15 and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Effect of acute caffeine supplementation before intermittent high-intensity exercise on cytokine levels and psychobiological parameters: A randomized, cross-over, placebo-controlled trial.

The present study aimed to verify the effects of caffeine supplementation on psychobiological parameters and its relationship with inflammatory cytokines in non-athlete subjects. We hypothesized that IL-10 may be responsible for the reduction in fatigue perception in response to caffeine supplementation. It was a randomized, double-blinded, cross-over, placebo-controlled study. Ten non-athlete subjects (26.9 ± 4.01 years old; 73.44 ± 9.57 kg; 15.94 ± 4.32 body fat kg) were evaluated. Sixty-min after caffeine (6 mg-1.kg-1 body mass) or placebo supplementation, high-intensity interval exercise test (1 min at 90% of Wmax and 2 min at 50% of Wmax) was performed to maximum voluntary exhaustion. Cytokine concentrations and psychobiological parameters were evaluated before (BE), immediately after (post-PE) and 1 h after exercise (1 h post-PE). We verify that IL-6 (0.35; 95% CI: 0.13 to 0.56; z = 3.24; p = 0.001; d = 1.14) and IL-10 (9.06; 95% CI 0.41 to 17.70; z = 2.05; p = 0.04; d = 1.12) increases post-PE in CAF group versus PLA group. Still, IL-10 levels were higher in CAF group 1 h post-PE (25.04; 95% CI: 8.95 to 41.31; z = 3.05; p = 0.002; d = 1.9) than PLA group. Moreover, 1 h post-PE vigor level was higher in the CAF group versus PLA group (4.53; 95% CI: 1.27 to 7.80; z = 2.72; p = 0.006; d = 0.46), and fatigue was lower in CAF group than PLA group (-5.08; 95% CI: -9.93 to -0.227; z = -2.05; p = 0.040; d = 0.67). We conclude that 1 h post-PE caffeine was able to decrease fatigue and increase vigor perception. IL-10 levels were higher 1 h post-PE in CAF group, suggesting, according to our hypothesis, that IL-10 may be associated with decrease fatigue perceptions after exercise.

Oxidative stress in bladder cancer: an ally or an enemy?

Bladder cancer (BC) is the most common cancer of the urinary tract and despite all innovations, remains a major challenge due to high morbidity and mortality. Genomic and epigenetic analyses allowed the discovery of new genes and pathways involved in the pathogenesis and regulation of BC. However, the effect on mortality has been modest and the development of new targets for BC treatment are needed. Recent evidence suggests that cancer cells are under increased stress associated with oncogenic transformation, with changes in metabolic activity and increased generation of reactive oxygen species (ROS). The increased amounts of ROS in cancer cells are associated with stimulation of cellular proliferation, promotion of mutations and genetic instability, as well as alterations in cellular sensitivity to anticancer agents. Since these mechanisms occur in cancer cells, there is a close link between oxidative stress (OS) and BC with implications in prevention, carcinogenesis, prognosis, and treatment. We address the role of OS as an enemy towards BC development, as well as an ally to fight against BC. This review promises to expand our treatment options for BC with OS-based therapies and launches this approach as an opportunity to improve our ability to select patients most likely to respond to personalized therapy.

A DSL-Based Approach for Detecting Activities of Daily Living by Means of the AGGIR Variables.

In this paper, we propose a framework for studying the AGGIR (Autonomie Gérontologique et Groupe Iso Ressources-Autonomy Gerontology Iso-Resources Groups) grid model, with the aim of assessing the level of independence of elderly people in accordance with their capabilities of performing daily activities as well as interacting with their environments. In order to model the Activities of Daily Living (ADL), we extend a previously proposed Domain Specific Language (DSL), by defining new operators to deal with constraints related to time and location of activities and event recognition. The proposed framework aims at providing an analysis tool regarding the performance of elderly/disabled people within a home environment by means of data recovered from sensors using a smart-home simulator environment. We perform an evaluation of our framework in several scenarios, considering five of the AGGIR variables (i.e., feeding, dressing, toileting, elimination, and transfers) as well as health-care devices for tracking the occurrence of elderly activities. The results demonstrate the accuracy of the proposed framework for managing the tracked records correctly and, thus, generate the appropriate event information related to the ADL.

Renal Procurement: Techniques for Optimizing the Quality of the Graft in the Cadaveric Setting.

PURPOSE OF REVIEW: Kidney transplantation is the best treatment for end-stage renal disease. However, due to organ shortage, suboptimal grafts are increasingly being used. RECENT FINDINGS: We carried out a review on the methods and techniques of organ optimization in the cadaveric setting. Donor care is the first link in a chain of care. Right after brain death, there is a set of changes, of which hormonal and hemodynamic changes are the most relevant. Several studies have been conducted to determine which drugs to administer, although in most cases, the results are not definitive. The main goal seems rather achieve a set of biochemical and hemodynamic objectives. The ischemia-reperfusion injury is a critical factor for kidney damage in transplantation. One of the ways found to deal with this type of injury is preconditioning. Local and remote ischemic preconditioning has been studied for various organs, but studies on the kidney are scarce. A new promising area is pharmacological preconditioning, which is taking its first steps. Main surgical techniques were established in the late twentieth century. Some minor new features have been introduced to deal with anatomical variations or the emergence of donation after circulatory death. Finally, after harvesting, it is necessary to ensure the best conditions for the kidneys until the time of transplantation. Much has evolved since static cold preservation, but the best preservation conditions are yet to be determined. Conservation in the cold has come to be questioned, and great results have appeared at temperatures closer to physiological.

Revisiting colorectal cancer animal model - An improved metastatic model for distal rectosigmoid colon carcinoma.

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 107 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, ß-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.

Prognostic value of subclassification (pT2 stage) of pathologically organ-confined prostate cancer: Confirmation of the changes introduced in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.

OBJECTIVE: The last edition of the AJCC staging system eliminated the pT2 subclassification of prostate cancer (PCa). Our objective was to evaluate the association of pT2 subclassification with the oncological results of patients with PCa who underwent radical prostatectomy (RP). MATERIAL AND METHODS: We evaluated 367 patients who underwent RP between 2009 and 2016, with pT2 disease in the final pathological evaluation. We assessed differences in rates of biochemical recurrence (BCR), metastasis and mortality between T2 substages (pT2a/b vs pT2c). RESULTS: Fifty-three (14.4%) patients presented pT2a/b disease and 314 (85.6%) pT2c disease. The mean follow-up time was 4.9 ± 2.6 years. Grade group scores (p = 0.1) and prostate specific antigen (PSA) (p = 0.2) did not differed between pT2 substages. The rate of BCR in pT2a/b and pT2c patients was 11.3% and 18.2%, respectively (p = 0.2). Five (9.4%) patients with pT2a/b and 45 (14.3%) with pT2c substage underwent salvage radiotherapy (p = 0.3). The rate of positive surgical margins did not differ between groups (p = 0.2). Seven (2.2%) patients with pT2c had lymph nodes or distant metastases. The overall survival was 92.5% and 93.6% in pT2a/b and pT2c, respectively (p = 0.2). CONCLUSION: Our results are in accordance with the changes introduced in the 8th edition of the AJCC staging system in which the pT2 subclassification was eliminated.

Diabetes mellitus and prostate cancer metabolism: Is there a relationship?

OBJECTIVE: Our aim was to evaluate the effects of glucose levels and diabetes mellitus in prostate cancer (PCa) biology. MATERIALS AND METHODS: Two PCa cell lines (LNCap and PC3) were cultured in RPMI medium with different glucose concentrations [5mM (LG) and 25mM (HG)]. Expressions of androgen receptor, Her2/neu and glucose transporters (GLUT1, 3, 5 and 12) were evaluated by flow cytometry. Proliferation rate was assessed by colorimetric assay MTT and cellular characterization was performed by haematoxylin and eosin staining. Additionally, we performed a cross sectional analysis of 704 patients undergoing radical prostatectomy who were divided into two groups (diabetic and non-diabetic). An analysis of clinical and histological data seeking to identify the differences on tumor aggressiveness between the two groups was performed. RESULTS: In LNCaP cell line, when the glucose concentration in the medium increased, there was an increased in AR expression. Regarding expression of Her2/neu receptor, medium's glucose concentration significantly changed the expression of this receptor in both PC3 and LNCaP cell lines. Growth rate was higher on the HG medium for both cell lines. The clinical study of patients undergoing radical prostatectomy revealed no relationship between the presence of diabetes and the development of more aggressive tumours. Diabetic patients had significantly higher prostatic volumes, however, no significant difference was found between the relapse risk classification or the ISUP classification between the two groups. CONCLUSIONS: Our results showed that medium glucose concentration could influence prostate cancer cells growing but not the aggressiveness.

Characterisation of several ankyrin repeat protein variant 2, a phosphoprotein phosphatase 1-interacting protein, in testis and spermatozoa.

Phosphoprotein phosphatase 1 (PPP1) catalytic subunit gamma 2 (PPP1CC2), a PPP1 isoform, is largely restricted to testicular germ cells and spermatozoa. The key to understanding PPP1 regulation in male germ cells lies in the identification and characterisation of its interacting partners. This study was undertaken to determine the expression patterns of the several ankyrin repeat protein variant 2 (SARP2), a PPP1-interacting protein, in testis and spermatozoa. SARP2 was found to be highly expressed in testis and spermatozoa, and its interaction with human spermatozoa endogenous PPP1CC2 was confirmed by immunoprecipitation. Expression analysis by RT-qPCR revealed that SARP2 and PPP1CC2 mRNA levels were significantly higher in the spermatocyte fraction. However, microscopy revealed that SARP2 protein was only present in the nucleus of elongating and mature spermatids and in spermatozoa. In spermatozoa, SARP2 was prominently expressed in the connecting piece and flagellum, as well as, to a lesser extent, in the acrosome. A yeast two-hybrid approach was used to detect SARP2-interacting proteins and a relevant interaction with a novel sperm-associated antigen 9 (SPAG9) variant, a testis and spermatozoa-specific c-Jun N-terminal kinase-binding protein, was validated in human spermatozoa. Given the expression pattern of SARP2 and its association with PPP1CC2 and SPAG9, it may play a role in spermiogenesis and sperm function, namely in sperm motility and the acrosome reaction.

Nanoparticle-Mediated, Light-Induced Phase Separations.

Nanoparticles that both absorb and scatter light, when dispersed in a liquid, absorb optical energy and heat a reduced fluid volume due to the combination of multiple scattering and optical absorption. This can induce a localized liquid-vapor phase change within the reduced volume without the requirement of heating the entire fluid. For binary liquid mixtures, this process results in vaporization of the more volatile component of the mixture. When subsequently condensed, these two steps of vaporization and condensation constitute a distillation process mediated by nanoparticles and driven by optical illumination. Because it does not require the heating of a large volume of fluid, this process requires substantially less energy than traditional distillation using thermal sources. We investigated nanoparticle-mediated, light-induced distillation of ethanol-H2O and 1-propanol-H2O mixtures, using Au-SiO2 nanoshells as the absorber-scatterer nanoparticle and nanoparticle-resonant laser irradiation to drive the process. For ethanol-H2O mixtures, the mole fraction of ethanol obtained in the light-induced process is substantially higher than that obtained by conventional thermal distillation, essentially removing the ethanol-H2O azeotrope that limits conventional distillation. In contrast, for 1-propanol-H2O mixtures the distillate properties resulting from light-induced distillation were very similar to those obtained by thermal distillation. In the 1-propanol-H2O system, a nanoparticle-mediated, light-induced liquid-liquid phase separation was also observed.

Amyloid precursor protein interaction network in human testis: sentinel proteins for male reproduction.

BACKGROUND: Amyloid precursor protein (APP) is widely recognized for playing a central role in Alzheimer's disease pathogenesis. Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood. APP is involved in several biological functions which might be potentially important for male fertility, such as cell adhesion, cell motility, signaling, and apoptosis. Furthermore, APP superfamily members are known to be associated with fertility. Knowledge on the protein networks of APP in human testis and spermatozoa will shed light on the function of APP in the male reproductive system. RESULTS: We performed a Yeast Two-Hybrid screen and a database search to study the interaction network of APP in human testis and sperm. To gain insights into the role of APP superfamily members in fertility, the study was extended to APP-like protein 2 (APLP2). We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses. We classified significant features related to the human male reproduction for the APP interacting proteins and identified modules of proteins with similar functional roles which may show cooperative behavior for male fertility. CONCLUSIONS: The present work provides the first report on the APP interactome in human testis. Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.

LAP1 is a crucial protein for the maintenance of the nuclear envelope structure and cell cycle progression.

Cell division in eukaryotes requires the disassembly of the nuclear envelope (NE) at the beginning of mitosis and its reassembly at the end of mitosis. These processes are complex and involve coordinated steps where NE proteins have a crucial role. Lamina-associated polypeptide 1 (LAP1) is an inner nuclear membrane protein that has been associated with cell cycle events. In support of this role, LAP1 has been implicated in the regulation of the NE reassembly and assembly of the mitotic spindle during mitosis. In this study, we demonstrated that LAP1 intracellular levels vary during the cell cycle in SH-SY5Y cells, and that LAP1 is highly phosphorylated during mitosis. It is also clear that LAP1 co-localized with acetylated α-tubulin in the mitotic spindle and with γ-tubulin in centrosomes (main microtubule organizing center) in mitotic cells. Moreover, LAP1 knockdown resulted in decreased number of mitotic cells and decreased levels of acetylated α-tubulin (marker of microtubules stability) and lamin B1. Additionally, it was possible to determine that LAP1 is important for centrosome positioning near the NE. These findings place LAP1 at a key position to participate in the maintenance of the NE structure and progression of the cell cycle.

Intramammary preparation of enrofloxacin hydrochloride-dihydrate for bovine mastitis (biofilm-forming Staphylococcus aureus).

BACKGROUND: Chronic bovine mastitis is linked to biofilm-producing Staphylococcus aureus (bp-Sa) or Staphylococcus coagulase-negative (bp-Scn). OBJECTIVES: Bp-Sa and bp-Scn were treated with intramammary preparations of either enrofloxacin HCl·2H2O-dimethyl-sulfoxide-chitosan (enro-C/DMSO/chitosan) or enro-C alone. Their potential to inhibit and degrade biofilm formation in vitro was also assessed. METHODS: Milk samples were obtained from the affected quarters in a herd. Phenotypical and genotypical identifications as biofilm-producing Staphylococcus species were carried out. Enro-C/DMSO/chitosan and enro-C alone were assessed to determine their in vitro efficacy in interfering with biofilm formation and their bactericidal effects. A prolonged eight-day treatment with a twice-daily intramammary insertion of 10 mL of enro-C/DMSO/chitosan or enro-C alone was set to evaluate the clinical and bacteriological cures on day 10 in 15 cows per group and the biofilm-inhibiting ability. RESULTS: Fifty-seven percent of the isolates were identified as Staphylococcus spp., of which 50% were bp-Sa, 46% bp-Scn, and 4% Staphylococcus pseudintermedius. One hundred percent of the S. aureus isolated and 77% of Staphylococcus coagulase-negative were biofilm producers. In both groups, the icaA and icaD biofilm-producing genes were identified. The experimental preparation could inhibit biofilm formation, degrade mature biofilms, and have well-defined microbicidal effects on planktonic and biofilm bacteria. The respective clinical and bacteriological cure rates were 100% and 80% for enro-C/DMSO/chitosan and 41.7% and 25% for enro-C alone. CONCLUSIONS: Enro-C/DMSO/chitosan eliminates bp-Sa and bp-Scn from cases of chronic bovine mastitis.

Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa.

BACKGROUND: Protein Ser/Thr Phosphatase PPP1CC2 is an alternatively spliced isoform of PPP1C that is highly enriched in testis and selectively expressed in sperm. Addition of the phosphatase inhibitor toxins okadaic acid or calyculin A to caput and caudal sperm triggers and stimulates motility, respectively. Thus, the endogenous mechanisms of phosphatase inhibition are fundamental for controlling sperm function and should be characterized. Preliminary results have shown a protein phosphatase inhibitor activity resembling PPP1R2 in bovine and primate spermatozoa. RESULTS: Here we show conclusively, for the first time, that PPP1R2 is present in sperm. In addition, we have also identified a novel protein, PPP1R2P3. The latter was previously thought to be an intron-less pseudogene. We show that the protein corresponding to the pseudogene is expressed. It has PPP1 inhibitory potency similar to PPP1R2. The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. We also confirm that PPP1R2/PPP1R2P3 are phosphorylated at Ser121 and Ser122, and report a novel phosphorylation site, Ser127. Subfractionation of sperm structures show that PPP1CC2, PPP1R2/PPP1R2P3 are located in the head and tail structures. CONCLUSIONS: The conclusive identification and localization of sperm PPP1R2 and PPP1R2P3 lays the basis for future studies on their roles in acrosome reaction, sperm motility and hyperactivation. An intriguing possibility is that a switch in PPP1CC2 inhibitory subunits could be the trigger for sperm motility in the epididymis and/or sperm hyperactivation in the female reproductive tract.

C reactive protein/Albumin ratio as predictor of prognosis in castration resistant metastatic prostate cancer.

OBJECTIVE: To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. MATERIALS AND METHODS: A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. RESULTS: The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. CONCLUSIONS: According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

Predicting bladder cancer risk in patients with hematuria. A single-centre retrospective study.

INTRODUCTION: The presence of blood in the urine should be promptly investigated to rule out urological malignancies, bladder cancer being the most frequent. Given its frequency among general population and the lack of unlimited health resources in an era of cost-effectiveness, it is important to prioritize patients with higher risk of malignancy. OBJECTIVES: To identify predictive factors of bladder cancer among patients presenting with hematuria. PATIENTS AND METHODS: We retrospectively reviewed 296 cases referred to our department for hematuria. We evaluated different demographic, clinical and ultrasound features to uncover possible associations with diagnosis of bladder cancer in those patients, to estimate the individual risk of being diagnosed with bladder cancer during the investigation of hematuria. RESULTS: A total of 296 patients were studied for hematuria between January 1, 2017 and December 31, 2019, 23.6% of those having ultimately bladder cancer confirmed after transurethral resection. Older age, male gender (OR 2.727, p = 0.069), a history of smoking (OR 3.84, p < 0.05), recurrent hematuria (OR 3.396, p < 0.05) and positive ultrasound exam for bladder cancer (OR 30.423, p < 0.05) were identified as predictors of bladder cancer in patients with hematuria. CONCLUSIONS: This study suggests that it is possible to reliably estimate the risk of bladder cancer in patients with hematuria, using clinical and imaging data to help defining who should be investigated first and in whom the investigation could be postponed.

Are Pretransplant Kidney Biopsies Safe?

BACKGROUND: Annually, about 500 kidneys are transplanted in Portugal. Despite some studies looking into the procurement biopsies' benefits (like the potential of predicting long term results and establishing a baseline), few have studied its risks, especially in the period between the harvest and the transplant. METHODS: A cross-sectional study, including all patients who received a kidney graft between the 2019 and 2020 at the University Hospital of Coimbra (n = 203). Biopsies were done using a polar double core puncture technique with 18-gauge needles. RESULTS: Fifty-six patients (27.6%) received a biopsied graft. The median postoperative hemoglobin fall was 2.8 g/dL; this fall was more pronounced in the group that received a biopsied kidney (3.2 g/dL vs 2.6 g/dL; P < .05). The number of transfusions needed during the hospital stay (2.2 U vs 1.3 U; P < .05) and the median length of stay (13.2 ± 8.4 vs 10.6 ± 5.8, P < .05) were greater in the biopsied group. Patients who received a biopsied kidney were older (median age of 57.3 vs 46.9). Cold ischemia time was greater in the biopsied group (19 hours vs 15.2 hours; P < .05). However, we did not find a relation between the age and the hemoglobin drop or blood transfusions. At discharge, renal function was not statistically different between the 2 groups (P was nonsignificant). CONCLUSIONS: Despite the biopsies' potential advantages, they are not without risks. This study showed a statistical association between harvest biopsies and higher risks of hemorrhage, regardless of age. When needed, procurement biopsies seemed safe for the recipients, but at the expense of increased patient surveillance and resource consumption.

Reduced levels of serum 25(OH)D3 are associated with tuberculosis positive cattle under conditions of high natural exposure to Mycobacterium bovis.

Serum vitamin D (25(OH)D3) concentrations of < 30 ng/mL in cattle are insufficient to induce an adequate immune response against intracellular pathogens, which suggests that the efficacy of the immune response may be highly dependent on the bioavailability of 25(OH)D3. This study shows an overview of both in vitro and in vivo 25(OH)D3-mediated immune modulation amongst dairy cattle naturally exposed to M. bovis. Tuberculin status was confirmed by interferon gamma release assay (IGRA), and natural exposure was demonstrated by polymerase chain reaction (PCR). Tuberculin (-) cattle have a higher serum concentration of 25(OH)D3 (X¯= 87.12 ng/mL) when compared to tuberculin (+) cattle (X¯ = 45.86 ng/mL). Reduced serum 25(OH)D3 levels are associated with the presence of bovine TB, and serum 25(OH)D3 levels of > 80 ng/mL are necessary to counteract infection by M. bovis. Kill assays were performed to evaluate in vitro 25(OH)D3 modulation of intracellular M. bovis growth in bovine macrophages, which showed that reduced serum 25(OH)D3 levels are associated with diminished mycobactericidal capacity in this experimental model. On the other hand, increased 25(OH)D3 in culture media enhances phagocytosis and nitric oxide production, which in turn improves capacity to combat M. bovis.

Identification and characterization of a neuronal enriched novel transcript encoding the previously described p60Fe65 isoform.

Fe65 is a multimodular adaptor protein that interacts with the cytosolic domain of the ß-amyloid precursor protein (APP), the major component of Alzheimer's disease (AD) senile plaques. In the work here presented, we describe the existence of a new Fe65 transcript variant (GenBank Accession EF103274). A unique 5' sequence of 69 nucleotides, spanning a region between exons 2 and 3 of the FE65 gene, was present in a yeast two-hybrid (YTH) clone from a human brain cDNA library. In silico analysis and RT-PCR revealed the presence of a novel exon of 133 bp, and we redefined the structure of the human FE65 gene. The novel exon 3a-inclusive transcript generates a shorter isoform, p60Fe65. The migration pattern of the p60Fe65 isoform was observed previously and attributed to an alternative translation initiation site within the p97Fe65 transcript. Here, we provide evidence for the origin of the previously unexplained p60Fe65 isoform. Moreover, Fe65E3a is expressed preferentially in the brain and the p60Fe65 protein levels increased during PC12 cell differentiation. This novel Fe65 isoform and the regulation of the splicing events leading to its production, may contribute to elucidating neuronal specific roles of Fe65 and its contribution to AD pathology.