Evaluating the effects of preoperative treatment with 5-alpha reductase inhibitors in holmium laser enucleation of the prostate.

INTRODUCTION AND AIM: Patients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. MATERIAL AND METHODS: A retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. RESULTS: A total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. CONCLUSIONS: Therapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings.

A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.

Summary: Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.

Women's leadership in clinical research: A retrospective observational study over two decades in Spain.

BACKGROUND AND OBJECTIVE: Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. MATERIALS AND METHODS: Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. MAIN OUTCOME: proportion of CI led by female doctors (FD) during the study period. SECONDARY OUTCOMES: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. DATA SOURCES: Research Ethics Committee (REC) and Human Resources Department registries. RESULTS: During the study, the REC approved 8466 protocols, 52% (4408/8466) were EC, the rest were NIR. Women led 39.7% (3360/8466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1391/4408) and 48.5% (1969/4058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. CONCLUSIONS: Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research.

Antimicrobial prophylaxis post-amniocentesis procedures in cattle: A randomized controlled equivalence study.

Amniocentesis is a routine procedure utilized on several species including human, equine, and bovine patients. Early assessment and discovery of new genetic traits in the cattle industry are highly desirable in order to accelerate genetic gain by shortening generational intervals. One of the main concerns from this procedure is the introduction of pathogenic bacterial contamination into the amniotic cavity thereby increasing the risks of spontaneous pregnancy losses post procedure. In this randomized controlled equivalence study, we have tested the effect of antimicrobial prophylaxis on the incidence of spontaneous abortions and contrasted it to untreated individuals post amniocentesis. On the treated group (n = 67) all heifers remained pregnant whereas 1 of the untreated group (n = 65) resulted in a spontaneous abortion during the study period. The latter represents 1.54% of pregnancy losses attributed to the risk associated to the amniocentesis procedure. However, the probability of inducing spontaneous abortion from the technique itself is not different to that of the contemporaneous population (n = 694) not undergoing amniocentesis viz., 1.59%. Following a two-tailed distribution, statistical analyses showed no significant differences across treatments (Fisher's exact test P = 0.49). The current prospective study indicates that performing amniocenteses on cattle have resulted in similar spontaneous pregnancy losses comparable to those of pregnant heifers without undergoing amniocentesis and regardless of antimicrobial use. In conclusion, prophylactic antimicrobials may not be applicable within the cattle amniocentesis framework.

Effects of free-fatty-acid content and saturation degree of the dietary oil sources on lipid-class content and fatty-acid digestibility along the gastrointestinal tract in broilers from 22 to 37 days of age.

The aim of the present study is to assess the effect of the free-fatty-acid (FFA) content and saturation degree of dietary fat (added at 6%) on the fatty-acid (FA) digestibility and lipid-class content along the gastrointestinal tract and excreta in broilers from 22 to 37 d of age. This is essential to determine the potential use of acid oils (refining by-products rich in FFA) in broiler diets as an alternative to crude oils. The study consisted of a 2 × 4 factorial arrangement, which included 2 fat sources (soybean oils - unsaturated, or palm oils - saturated) and 4 levels of FFA (5, 15, 35, and 50%). Samples of digestive content of the gizzard, duodenum, jejunum, ileum and of the excreta were obtained at 37 d of age. Irrespective of the dietary fat source, more than 80% of total FA (TFA) was absorbed in the jejunum. Broilers fed with unsaturated diets had a higher absorption efficiency of FA than did those fed with saturated diets. This conclusion is supported by the lower FFA content and the higher TFA and polyunsaturated FA (PUFA) digestibility coefficients in the ileum (P < 0.001) observed in the former group. The dietary FFA level did not affect the FA absorption process as much as the dietary fat source did. This was supported by the lack of statistical differences among the diets with a similar saturation degree but rather different levels of FFA, for TFA, saturated FA, and PUFA digestibility coefficients both in the jejunum and ileum. However, the interactions reported in the ileum for triacylglycerol and diacylglycerol contents (P < 0.001), as well as for monounsaturated FA digestibility coefficients (P < 0.05) show that the dietary FFA content affects the FA absorption process. The present results show that the inclusion of acid oils in grower-finisher broiler diets with FFA levels up to 35% does not have a negative impact on the FA absorption process.

Optimization of a 5-day fixed-time embryo transfer (FTET) protocol in heifers I. Manipulation of circulating progesterone through reutilization of intravaginal progesterone devices during FTET.

The objectives of the present study were to: 1) compare the reproductive efficiency of embryo transfer (ET) recipients after synchronization of estrus or a 5-day synchronization of ovulation protocol for fixed time ET (FTET), and 2) determine the effect of reutilization of intravaginal P4 devices (CIDRs), up to four times, in a 5-day FTET protocol. In Experiment 1, 817 dairy heifers were assigned to one of three groups: PGF + estrus detection, 5-d FTET protocol with new (1.38 g P4) or 2nd use CIDR (previously used once for 5 d). Fresh in vitro produced embryos were transferred 7 ± 1 day after estrus (PGF + estrus) or GnRH (5-day FTET). Utilization rate (transferred/treated) was greater (P < 0.001) in heifers submitted to FTET compared to ET after estrus, however pregnancies per ET (P/ET) were not different (P > 0.10). As a result, pregnancy per treated (P/treated) recipient was greater (P < 0.05) in heifers in the 5-day FTET protocol. In Experiment 2, 40 dairy heifers without a corpus luteum (CL) were randomly allocated into one of four groups using new, 2nd use, 3rd use (previously used twice for 5 d/each), or 4th use (previously used thrice for 5 d/each) CIDRs. Circulating P4 was reduced (P < 0.01) with each reutilization. In Experiment 3, ovarian follicular dynamics were evaluated in 238 dairy heifers submitted to a 5-day protocol with either new, 2nd use, 3rd use or 4th use CIDRs at random stages of the estrous cycle. Prostaglandin F2α (PGF) was administered at CIDR removal and again 24 h later. Ovulation was induced by GnRH treatment 72 h after CIDR removal. Preovulatory follicle diameter increased (P < 0.001) progressively with increasing CIDR reutilization. Ovulation rate did not differ between treatments, however, interval from CIDR removal to ovulation decreased (P < 0.001) in heifers receiving 3rd and 4th use CIDRs compared to new or 2nd use. Finally, in Experiments 4 and 5, 1203 heifers submitted to a 5-day FTET protocol were randomly assigned to receive either a new CIDR, a 3rd use CIDR (Experiment 4) or a 4th use CIDR (Experiment 5). Despite the increase in CL volume on D5 in heifers treated with 3rd use (P = 0.03) or 4th use CIDRs (P < 0.01), there were no differences (P > 0.05) in utilization rate, P/ET, or P/treated. Thus, use of a 5-day FTET synchronization protocol improves reproductive efficiency by increasing recipient utilization, and reutilization of CIDRs up to four times in recipient dairy heifers does not compromise reproductive performance.

Development and psychometric properties of the "Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales" in adolescents.

Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity-the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test-retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS-the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = - 0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents.

Hepatic mRNA expression of enzymes associated with progesterone metabolism and its impact on ovarian and endocrine responses in Nelore (Bos indicus) and Holstein (Bos taurus) heifers with differing feed intakes.

The aim of this study was to evaluate circulating progesterone concentration (P4), LH pulsatility and ovarian follicular dynamics in Nelore (B. indicus) and Holstein (B. taurus) heifers under high (HDMI) and low (LDMI) dry matter/energy intakes. In addition, the effects of dry matter/energy intake and breed on hepatic expression of six genes associated with P4 metabolism (AKR1C4, AKR1D1, CYP3A4, CYP2C19, SRD5A1, and SRD5A3) was evaluated. Heifers received an intravaginal P4 device (1 g), 2 mg of estradiol benzoate (EB) i.m. and 500 µg of PGF2α at the begging of the synchronization protocol (D0). Eight days later, the P4 device was removed and all heifers received 1 mg of EB 24h later. Regardless of dry matter/energy intake, the number of recruited follicles was greater in Nelore than in Holstein heifers. In contrast, the maximum diameter of the dominant follicle was greater in Holstein than in Nelore heifers. Circulating P4 concentrations were greater in Nelore than in Holstein from D2 to D9, and in heifers receiving LDMI than those receiving HDMI from D1 to D8 of hormonal protocol. In addition, Holstein heifers had greater LH pulsatility and area under the curve of LH peaks compared to Nelore heifers. However, no effects were observed for LH values between feed intake levels. Interestingly, Holstein heifers had higher expression of SRD5A1, AKR1C4, AKR1D1 than Nelore heifers; whereas, for Nelore heifers, only the expression of CYP3A4 was higher compared to Holstein heifers. In conclusion, there are important differences in the follicular dynamics, circulating P4 and LH pulsatility concentrations that need to be considered during synchronization protocols for Nelore and Holstein breeds. More importantly, these differences appear to be at least partially modulated by the level of feed intake and the contrasting enzyme system in the liver involved with P4 metabolism between these cattle breeds.

Effects of dietary free fatty-acid content and saturation degree on lipid-class composition and fatty-acid digestibility along the gastrointestinal tract in broiler starter chickens.

The aim of the present study is to assess the effect of the dietary free fatty acid (FFA) content and dietary fat saturation degree on the fatty-acid (FA) digestibility and lipid-class content along the gastrointestinal tract and excreta in broiler chickens. The 8 experimental diets resulted from replacing crude soybean oil with soybean acid oil from chemical refining, or crude palm oil with palm FA distillate from physical refining. Thus, there were 4 soybean and 4 palm diets with 6% added fat varying in their FFA% (5, 15, 35, and 50%). Samples of digestive content (gizzard, duodenum, jejunum, and ileum) and excreta were collected at 14 D for the determination of the FA digestibility and lipid-class content. The total FA digestibility coefficients reported for the chickens fed S diets in the jejunum, ileum, and excreta were higher than for those fed P diets (P ≤ 0.02). The general greater digestibility of the unsaturated diets was mainly explained by a higher contribution of the ileum to the absorption of saturated FA. The dietary FFA content mainly affected the FA absorption process. The diets with 50% FFA presented lower saturated FA digestibility coefficients in the jejunum and ileum (P ≤ 0.03), and higher content of FFA in the ileum and excreta (P ≤ 0.014), in comparison to the diets with 5% FFA. The 15% FFA diets were not different from the 5% FFA diets, regarding the saturated FA digestibility in the jejunum and excreta, and the FFA content in the ileum and excreta. It was concluded that unsaturated diets with moderate content of dietary FFA (up to 15%) could be used in broiler-chicken starter diets, as they led to similar FA absorption and performance results to the diets with the lowest dietary FFA content. From the present study, it has also been concluded that dietary saturated FA content has a greater impact on FA absorption than the dietary FFA content has.

Effects of zoledronic acid and dexamethasone on early phases of socket healing after tooth extraction in rats: A preliminary macroscopic and microscopic quantitative study.

BACKGROUND: The exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is still unknown. The aim of this paper was to investigate the effects of zoledronic acid and dexamethasone on the early phases of socket healing in rats subjected to tooth extractions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into 2 groups: pharmacologically treated group (T, n=20) and non-pharmacologically treated group (C, n=10). T group rats received 0.1 mg/Kg of zoledronic acid (ZOL) and 1 mg/Kg of dexamethasone (DEX) three times a week for 10 consecutive weeks. C group rats were infused with vehicle. After 9 weeks from the first infusion, first maxillary molars were extracted in each of the rats. Quantitative macroscopic and microscopic analysis was performed to evaluate socket healing 8 days after extraction. RESULTS: Pharmacologically treated rats showed significant inhibition of bone remodeling. Connective tissue/alveolar bone ratio, osteoclast number and woven bone deposition were significantly reduced in group T compared to group C. Conversely, the proportion of necrotic bone was higher in group T compared to group C (0.8% and 0.3%, respectively. P=0.031). ZOL plus DEX do not cause gross effects on socket healing at a macroscopic level. CONCLUSIONS: Our findings confirmed that exposure to ZOL plus DEX impairs alveolar wound repair. Inhibition of osteoclastic resorption of socket walls after tooth extraction and the inability to dispose of the necrotic bone may be considered the initial steps of MRONJ onset.

Absorption and diffusion of a 645 nm diode laser beam in the bone. An ex vivo study.

The present preliminary ex vivo study aims to assess the possible interaction between complex biological systems and laser light, through irradiation of different hard tissue samples. A 645 nm wavelength diode laser was adopted to perform the present evaluation. Due to known similarities to human tissues, swine tissue samples were used. Two samples of cortical bone measuring 4.4 mm and 4.7 mm of thickness and 2 samples of spongeous bone measuring 2.45 mm and 2.9 mm were harvested for the analysis of hard tissues. Mean absorption values were as follows: 128.82 mW standard deviation 8.74 for 2.45 mm spongeous bone sample; 132.34 mW standard deviation 7.66 for 2.9 mm spongeous bone sample; 140.59 mW standard deviation 5.97 for 4.4 mm cortical bone sample and 152.20 mW standard deviation 3.36 for 4.7 mm mucosa and cortical bone sample. Red-light laser with 645nm wavelength has the ability to reach cells in each layer of measured tissues.

Evolution of lipid classes and fatty acid digestibility along the gastrointestinal tract of broiler chickens fed different fat sources at different ages.

The aim of the present study is to evaluate the effect of the dietary fat saturation degree and age on the lipid class (TAG, DAG, MAG, and FFA) composition and fatty acid digestibility along the gastrointestinal tract (GIT) and excreta in broiler chickens. A total of 120 one-day-old female broiler chickens were randomly distributed in 2 dietary treatments (6 cages/treatment), which resulted from the supplementation of a basal diet with 6% of soybean oil or palm oil. Two digestibility balances were carried out at 14 and 35 d and fatty acid digestibility and lipid class composition were determined in the gizzard, duodenum, jejunum, ileum, and excreta. Along de GIT, both fatty acid digestibility and lipid class composition were influenced by the dietary fat source and the age of the chickens. The absorption of the unsaturated fat was more efficient and faster than it was for the saturated fat. The ability of adult chickens to absorb fat was higher than for young chickens. The results show that the duodenum is the main place of fat digestion (hydrolysis), and the jejunum the main place of fat absorption. The role of the ileum on fat absorption is very important, as it is the last segment of the GIT where the absorption of fatty acids has been described. Thus, it was the contribution of the ileum that was responsible for the higher fat utilization observed for animals fed the unsaturated diet than for those fed the saturated diet at 14 d, and it was also responsible for the improvement on the utilization of the saturated diet between 14 and 35 d. All the results suggest that the absorption of fatty acids is more limiting than is hydrolysis, because the main differences were observed in the jejunum and ileum, where the absorption of fatty acids takes place.

Infections related to healthcare in patients hospitalized in a Urology service: resistance patterns and adequacy of empirical antibiotic treatment as a prognostic factor. / Infecciones relacionadas con la asistencia sanitaria en pacientes ingresados en un servicio de Urología: patrones de resistencia y adecuación del tratamiento antibiótico empírico como factor pronóstico.

OBJECTIVES: To evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. METHOD: A prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analysed. RESULTS: Out of 6,546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. CONCLUSIONS: The selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

New magnetostratigraphic evidence for the age of Acheulean tools at the archaeo-palaeontological site "Solana del Zamborino" (Guadix - Baza Basin, S Spain).

The sedimentary record in the Guadix-Baza Basin (southern Spain) has proved to be a great source of information for the Miocene through the Pleistocene periods, due to the abundant faunal remains preserved, in some cases associated with lithic tools. The Solana del Zamborino (SZ) section has been the subject of controversy ever since a magnetostratigraphic analysis resulted in an age of 750-770 Kyr for Acheulean tools, a chronology significantly older than the ~600 Kyr established chronology for the first Acheulean record in Europe. Although recent findings at the "Barranc de la Boella" site (north-east of the Iberian Peninsula) seem to indicate that an earlier introduction of such technique in Europe around 0.96-0.781 Ma is possible, the precise age of the classical site at SZ is still controversial. The aim of this paper is to constrain the chronology of the site by developing a longer magnetostratigraphic record. For this purpose, we carried out an exhaustive sampling in a new succession at SZ. Our results provide a ~65 m magnetostratigraphic record in which 4 magnetozones of normal polarity are found. Our new magnetostratigraphic data suggest an age range between 300-480 Kyr for the lithic tools, closer to the age of traditional Acheulean sites in Europe.