Effects of orexins on 17β-estradiol synthesis and P450 aromatase modulation in the testis of alpaca (Vicugna pacos).

The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T) into estrogens (E), expressed as 17β-estradiol. The presence and localization of this key enzyme have not been described before in the South American camelid alpaca (Vicugna pacos). In our previous studies of the expression and biological effects of orexin A (OxA) and OxB on the alpaca testis demonstrated that OxA, via its specific receptor 1 (OX1R), stimulated T synthesis. In order to extend these findings, we presently explored the presence and localization of ARO in the alpaca male gonad, and the possible correlation between ARO and the orexinergic complex. Western blotting and immunohistochemistry demonstrated the presence of ARO in tissue homogenates and its localization in the tubular and interstitial compartments of the alpaca testis, respectively. The addition of OxA to fresh testicular slices decreased the 17β-estradiol E levels. This effect was annulled by the sequential addition of the selective OX1R antagonist, SB-408124. OxB incubation did not have any effect on the biosynthesis of E. Furthermore, the OxA-mediated down-regulation of E secretion could be ascribed to ARO inhibition by exogenous OxA, as indicated by measurement of ARO activity in tissue slices incubated with OxA. Overall, our findings suggest that locally secreted OxA interacting with OX1R could indirectly inhibit ARO activity, disabling the conversion of T to E, and consequently lowering E biosynthesis and increasing the production of T in mammalian testis

LCA Analysis of Renewable Domestic Hot Water Systems with Unglazed and Glazed Solar Thermal Panels

Abstract The paper presents a from-cradle-to-grave LCA (Eco-Indicator 99, Egalitarian Approach) study for two domestic solar hot water systems (DSHWS): a traditional one with glazed panels and a system with unglazed solar collectors. Both systems are coupled with a 300-liters storage tank. The performed LCA returns an EI99 equal to 198.19 for the traditional glazed DSHWS and equal to 18.28 for the unglazed one. For each DSHWS the energy, CO 2 and economic pay-back times were calculated for three different locations (Rome, Madrid and Munich) in order to take into account the influence of local climate on the solar panels yields. The payback times took as basis of comparison two competitive technologies: the natural gas and the electrical boiler

Potential role of orexin A binding the receptor 1 for orexins in normal and cryptorchid dogs.

Background: Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity. Orexins modulate a great variety of body functions, such as the reproductive mechanism. The purpose of the present research was to study the presence of OxA and its receptor 1 and their possible involvement in the canine testis under healthy and pathological conditions. Methods: This study was performed using adult male normal dogs and male dogs affected by unilateral cryptorchidism. Tissue samples were collected from testes and were divided into three groups: normal, contralateral and cryptic. The samples were used for immunohistochemistry, Western blot and in vitro tests for testosterone evaluation in normal and pathological conditions. Results: OxA-immunoreactivity (IR) was described in interstitial Leydig cells of the normal gonad, and Leydig, Sertoli cells and gonocytes in the cryptic gonad. In the normal testis, OX1R-IR was described in Leydig cells, in pachytene and second spermatocytes and in immature and mature spermatids throughout the stages of the germ developing cycle of the male gonad. In the cryptic testis OX1R-IR was distributed in Leydig and Sertoli cells. The presence of prepro-orexin and OX1R was demonstrated by Western blot analysis. The incubation of fresh testis slices with OxA caused the stimulation of testosterone synthesis in the normal and cryptic gonad while the steroidogenic OxA-induced effect was cancelled by adding the selective OX1R antagonist SB-408124. Conclusions: These results led us to hypothesise that OxA binding OX1R might be involved in the modulation of spermatogenesis and steroidogenesis in canine testis in healthy and pathological conditions

Effect of colostrum and milk on small intestine expression of AQP4 and AQP5 in newborn buffalo calves.

Functional studies indicate differences in newborn gastrointestinal morphology and physiology after a meal. Both water and solutes transfer across the intestinal epithelial membrane appear to occur via aquaporins (AQPs). Given that the physiological roles of AQP4 and AQP5 in the developing intestine have not been fully established, the objective of this investigation was to determine their distribution, expression and respective mRNA in the small intestine of colostrums-suckling buffalo calves by using immunohistochemistry, Western blot, and reverse transcriptase-PCR analysis. Results showed different tissue distribution between AQP4 and AQP5 with the presence of the former along the enteric neurons and the latter in the endocrine cells. Moreover, their expression levels were high in the ileum of colostrum-suckling buffalo calves. The data present a link between feeding, intestinal development and water homeostasis, suggesting the involvement of these channel proteins in intestinal permeability and fluid secretion/absorption during this stage of development after birth

N-(1-carbamoyl-2-phenylethyl) butyramide reduces antibioticinduced intestinal injury, innate immune activation and modulates microbiota composition

The use/misuse of antibiotics leads to pathological features referring to antibiotic-induced intestinal injury (AIJ), a clinical issue that plays a prominent role in the development of severe digestive disturbances. AIJ is characterized by loss of intestinal architecture and function, dysbiosis and bacterial translocation into the liver, triggering hepatic inflammation. This study aimed at determining the beneficial effect of N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), a butyrate releasing compound, in ceftriaxone-induced intestinal injury. To this purpose, mice receiving ceftriaxone (8 g∙kg−1/die, per os) for five days, were treated with FBA (212,5 mg∙kg−1/die, per os) for five or fifteen days. FBA modulated key players of innate immunity in antibiotic-injured gut tissues, reducing inflammatory process and improving the anti-inflammatory and resolving pattern. FBA also improved colonic architecture and intestinal integrity. Interestingly, we also observed a remodeling of gut microbiota composition related to an increase of metabolic pathways related to lactate and butyrate production. At mechanistic level, FBA induced histone acetylation and increased the expression of GPR43 and monocarboxylate transporter 1 in colon. Our data clearly demonstrated that FBA has multiple converging mechanisms in limiting intestinal and hepatic alterations to counteract AIJ

Communication and visiting policies in Italian intensive care units during the first COVID-19 pandemic wave and lockdown: a nationwide survey

Background: During the first coronavirus disease 2019 (COVID-19) pandemic wave, an unprecedented number of patients with respiratory failure due to a new, highly contagious virus needed hospitalization and intensive care unit (ICU) admission. The aim of the present study was to describe the communication and visiting policies of Italian intensive care units (ICUs) during the first COVID-19 pandemic wave and national lockdown and compare these data with prepandemic conditions. Methods: A national web-based survey was conducted among 290 Italian hospitals. Each ICU (active between February 24 and May 31, 2020) was encouraged to complete an individual questionnaire inquiring the hospital/ICU structure/organization, communication/visiting habits and the role of clinical psychology prior to, and during the first COVID-19 pandemic wave. Results: Two hundred and nine ICUs from 154 hospitals (53% of the contacted hospitals) completed the survey (202 adult and 7 pediatric ICUs). Among adult ICUs, 60% were dedicated to COVID-19 patients, 21% were dedicated to patients without COVID-19 and 19% were dedicated to both categories (Mixed). A total of 11,102 adult patients were admitted to the participating ICUs during the study period and only approximately 6% of patients received at least one visit. Communication with family members was guaranteed daily through an increased use of electronic devices and was preferentially addressed to the same family member. Compared to the prepandemic period, clinical psychologists supported physicians more often regarding communication with family members. Fewer patients received at least one visit from family members in COVID and mixed-ICUs than in non-COVID ICUs, l (0 [0–6]%, 0 [0–4]% and 11 [2–25]%, respectively, p < 0.001). Habits of pediatric ICUs were less affected by the pandemic. Conclusions: Visiting policies of Italian ICUs dedicated to adult patients were markedly altered during the first COVID-19 wave. Remote communication was widely adopted as a surrogate for family meetings. New strategies to favor a family-centered approach during the current and future pandemics are warranted

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Thermodynamic analysis of a hot air open cycle engine with a camshaft drive

Proceedings of the 9th Internatinal Stirling Engine Conference - Paper ISEC-99005, Pilanesburg, Republic of South Africa, June 199