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In this work, we present the application of ultrashort and intense laser pulses (110 fs @ 1 kHz; up to 1.1 mJ/pulse) to the micromachining of ceramics, specifically RubalitTM708S, a material based on alumina and widely used as a substrate in microelectronics. The mechanism for removing material is the so called direct ablation. It differs from thermal ablation of conventional lasers in the practically total absence of thermal effects which produces a remarkable increase of quality and precision of the machining. By means of an optical diffraction-based technique we find out the energy density threshold to work in the direct ablation regime. Adjusting the energy per pulse as well as the number of pulses, we are able to drill holes of the desired diameter and depth. In addition, processing is developed in air. We also demonstrate that high quality fs-laser micromachining is suitable for every ceramic, whatever the mechanical properties, with similar working parameters. In order to show this point, we have also processed sintered SiN, a material of wide-ranging interest in industry.En este trabajo presentamos la aplicación de pulsos láser ultracortos (110 fs @ 1 kHz; hasta 1.1 mJ/pulso) al micromecanizado de materiales cerámicos, en concreto RubalitTM708S, un material compuesto principalmente de alúmina y empleado en la industria microelectrónica. El mecanismo de eliminación de material es la ablación directa, que difiere de la ablación térmica empleada por los láseres convencionales en la prácticamente total ausencia de efectos térmicos, lo que redunda en un aumento significativo de la precisión y calidad del mecanizado. Mediante técnicas basadas en la difracción óptica determinamos el umbral de energía necesario para que tenga lugar el proceso de ablación directa. Con ese dato y regulando la energía por pulso y el número de pulsos somos capaces de producir mecanizados del diámetro y profundidad deseados. Además, el procesado se realiza en aire. Demostramos que es posible ejecutar micromecanizado de calidad mediante este procedimiento en cualquier material cerámico, independientemente de sus propiedades mecánicas, variando ligeramente los parámetros del proceso. En este caso, además de la alúmina hemos procesado SiN sinterizado, un material de uso extendido en la industria.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse., Competing Interests: Conflict of interest A. Ibáñez has received research support from or served as speaker or advisor for Janssen-Cilag, Lundbeck and Otsuka. A. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Sanofi-Aventis, Exeltis, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), and the Basque Government, J. Saiz-Ruiz has been as speaker for and on the advisory boards of Adamed, Lundbeck, Servier, Medtronic, Casen Recordati, Neurofarmagen, Otsuka, Indivior, Lilly, Schwabe, Janssen and Pfizer, outside the submitted work. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda, Pilar A. Saiz has been a consultant to and/or has received honoraria or grants from Adamed, CIBERSAM, European Comission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas and Servier. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received  grants from: Instituto de Salud Carlos III,  Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini. The rest of the authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Congestive heart failure (CHF) is a common complication in patients with chronic kidney disease (CKD). In addition to classical risk factors (e.g. age and pre-existing cardiac diseases), other potential reversible abnormalities linked to CKD such as anaemia, volume overload, or vascular access placement may also influence the incidence and severity of acute exacerbations of CHF., Objective: This study aims to determine the incidence and main determinants of CHF in a cohort of patients with stage 4-5 pre-dialysis CKD., Patients and Method: The study group consisted of 562 patients (mean age: 65 +/- 15 years, 260 females, 31% diabetics). Native arteriovenous fistulas (AVF) were created in 160 patients who chose haemodialysis as the initial technique for renal replacement therapy. The main outcome variables were: acute decompensated CHF (defined by standard criteria), dialysis initiation (planned and unplanned), and death before dialysis initiation. In addition to demographics, comorbidities, and clinical and biochemical data, AVF creation was also included as a potential determinant of CHF in multiple logistic regression models., Results: Ninety-five patients (17%) developed at least one episode of acute decompensated CHF, and the incidence rate was 19 episodes per 1000 patient-years. In addition to classical risk factors (age, female sex, obesity, diabetes, and previous history of CHF or coronary artery disease), creation of a successful AVF significantly increased the risk of CHF (OR=9.54, 95% CI: 4.84-18.81, P<.0001). In 47 out of 95 patients who developed CHF, a functioning AVF had previously been created, 92% of which were upper arm native AVF, with a median of 51 days between the surgical procedure and CHF episode. The mortality of patients with CHF was similar to that of the rest of the study patients, although unplanned dialysis initiation was significantly more frequent in those who developed CHF., Conclusions: Acute decompensated CHF episodes are common in pre-dialysis CKD patients. In addition to classical risk factors, pre-emptive AVF placement was strongly associated with the development of CHF.

Background: Laparoscopic adjustable gastric banding (LAGB) can impair esophageal peristalsis and can also cause a lack of relaxation of the lower esophageal sphincter, possibly leading to esophageal dilation. The aim of the present study was to determine the incidence of megaesophagus, the role of preoperative manometry in predicting its occurrence, and the management of megaesophagus after gastric banding in the setting of a research clinic., Methods: We performed a retrospective review of a prospectively collected database. A total of 257 patients underwent LAGB from January 2002 to December 2006. The incidence of megaesophagus, its relationship to the preoperative esophageal manometry and upper gastrointestinal series findings, and the treatment of patients with this complication were analyzed., Results: Of the 257 patients, 5 (1.9%) presented with megaesophagus after gastric banding. The mean interval to development was 32 months (range 24-36). The diagnosis was made using the symptoms, signs, and upper gastrointestinal series findings. The preoperative esophageal manometry findings were normal in 4 (80%) of these 5 patients, and 1 patient (20%) had a nonspecific motility disorder. The mean age was 54.5 years (range 30-76). The mean preoperative weight was 127.1 kg (range 112.7-145.9), and the body mass index was 43.2 kg/m2 (range 41-49). In all cases, the management of megaesophagus was gastric band removal. All the patients improved partially after band deflation but required band removal because of continued symptoms., Conclusion: Megaesophagus is a possible late complication after LAGB. The preoperative manometry results cannot predict for its occurrence. The management of megaesophagus caused by LAGB requires, in most cases, band removal.

Purpose: To expand the understanding of the association between recent health-risk behaviors and a history of forced sexual intercourse, using a nationally representative sample of female and male high school students., Methods: Data were from the 2003 National Youth Risk Behavior Survey, a nationally representative biennial survey of U.S. high school students. Lifetime history of forced sex, recent physical dating violence, and health-risk behaviors (substance use, diet-related behaviors, violence-related behaviors, and health promoting behaviors) were assessed. Analyses were stratified by gender and controlled for grade and race/ethnicity., Results: Of students surveyed, 8.9% reported ever being forced to have sex. One in eight females and one in 16 males experienced forced sex in their lifetime. For females and males, a history of forced sex was associated with experiencing physical dating violence and suicidal ideation in the 12 months preceding the survey and with substance use in the previous 30 days. Female victims were not as likely as female nonvictims to have participated in team sports during the previous 12 months. Male victims were more likely than male nonvictims to have fasted for more than 24 hours to lose weight during the previous 30 days., Conclusions: A lifetime history of forced sex is associated with recent dating violence and participation in unhealthy behaviors. Services and intervention programs for victimized youth should address health concerns that have been linked to sexual assault. Such programs would provide opportunities for early intervention with lasting implications for improved health.

Liver endothelial cells possess fenestrae, which are pores supported by a cytoskeleton ring composed of actin and myosin. Fenestrae are dynamic structures that can contract or dilate, although the mechanism for this phenomenon remains to be elucidated. Staining of actin and/or of myosin permitted measurement of fenestral diameter and area in cultured rat liver endothelial cells using digitized video-intensified fluorescence microscopy with image analysis. Within 1 minute of incubation with 0.1 micromol/L serotonin, fenestral diameter and area decreased by 24 +/- 5% and 56 +/- 7%, respectively. Contraction of fenestrae by serotonin was inhibited by chelation of extracellular Ca2+ with EGTA and by addition of Ca2+ channel blockers, such as dilthiazem and verapamil. The response of fenestrae to serotonin was mimicked by addition of a Ca2+ ionophore, A23187. Serotonin inhibited cAMP production, had no effect on inositol phosphate production, and activated phospholipase A2, causing release of arachidonic acid. These results suggest that contraction of fenestrae is associated with Ca2+ influx. In response to 0.1 micromol/serotonin, intracellular Ca2+ levels increased within 3 to 5 seconds from 150 nmol/L to >400 nmol/l followed by rapid phosphorylation of the 20-kd subunit of myosin light chain; both events dependent on extracellular Ca2+.

Phosphatidylcholine (PC) translocation was studied in rat liver canalicular plasma membrane vesicles using a fluorescent PC analogue that permitted the quantitation of asymmetric PC distribution in the outer and inner leaflet of the vesicles. PC translocation to the outer leaflet of the canalicular membrane was stimulated by ATP and an ATP-regenerating system in a time and temperature-dependent manner resulting in 200 pmol PC translocated/mg protein per 30 min. A non-hydrolyzable ATP analogue did not support translocation. Translocating activity was observed with PC but not with phosphatidylethanolamine and was specific for inside-out oriented canalicular membrane vesicles. Addition of taurocholate (10 microM), a micelle-forming bile acid, enhanced ATP-dependent PC translocation 1.5 +/- 0.1-fold, whereas addition of taurodehydrocholate (10 microM), a non-micelle-forming bile acid, did not. These results indicate the presence of an ATP-dependent transporter that "flips" phosphatidylcholine from the inner to the outer leaflet of the rat bile canalicular plasma membrane from where it can become associated with bile acids in the canalicular lumen, thereby enhancing ATP-dependent flipping activity. Several lines of evidence suggest that the transporter is Mdr2 P-glycoprotein.

The contraction of hepatic endothelial cell fenestrae after exposure to serotonin is associated with an increase in intracellular Ca2+ which is derived from extracellular Ca2+, is inhibited by pertussis toxin and is not associated with activation of phosphoinositol turnover or cAMP. Using cell-attached and excised patches in primary cultures of rat hepatic endothelial cells, we identified a serotonin-activated channel with conductance of 26.4+/-2.3 pS. The channel was also permeant to Na+, K+ and Ca++ but not to anions. In cell-attached patch recordings, addition of serotonin to the bath significantly increased channel activity with Ca2+ or Na+ as the charge-carrying ions. This channel provides a mechanism whereby serotonin can raise the cytosolic Ca2+ concentration in hepatic endothelial cells.

Eight-week-old rats had twofold higher hepatic ligandin concentration than 10-day-old animals as determined immunologically and by steroid isomerase and glutathione S-transferase assays. Increased ligandin content was accompanied by parallel increase in subunit synthesis as determined by [3H]leucine incorporation into each subunit relative to incorporation into total cytosolic proteins. The mRNA content for each ligandin subunit was twofold higher in older animals as determined by cell-free in vitro translation followed by immunoprecipitation and dot hybridization using a ligandin cDNA probe. When poly A mRNA from the postmitochondrial fraction of liver from young or old rats was subjected to agarose gel electrophoresis under denaturing conditions and hybridized to ligandin cDNA probe, a single 11 S band was obtained. With RNA from total liver, an additional 13 S band was obtained, suggesting the existence of a precursor form of ligandin mRNA. Since precursor polypeptides were not observed with RNA from total liver in cell-free in vitro translation systems, the precursor form requires processing to the 11 S form before the mRNA becomes functional.

Ligandin (GSH-S-transferase B), an abundant intracellular soluble protein in rat proximal tubules, hepatocytes, and small intestinal mucosal cells, is believed to be a component of an organic anion transport system. Its presence in urine was determined immunologically and catalytically in adult, female, Sprague-Dawley rats that were given mercuric chloride or potassium dichromate. These nephrotoxic agents produce severe renal failure, with epithelial necrosis in the proximal tubule. Mercuric chloride perferentially injures the terminal part of the proximal tubule, while potassium dichromate damages more proximal segments. Ligandinuria was consistently detected immunologically and catalytically from 6 to 24 hr following injection of mercuric chloride. Potassium dichromate administration did not result in immunologically detectable liganduria; however, GSH-S-transferase activity, which provides a more sensitive assay, was frequently detected. The findings are consistent with immunofluorescent localization of ligandin in the proximal tubule. Immunologic or enzymatic measurement of ligandin in urine may provide a sensitive index of acute injury to the proximal tubule.