Trans-Epithelial Transport,Metabolism, and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met)

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.     

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.     

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

ObjectiveSensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium.DesignCross-sectional study nested in the 2017 “Delirium Day” project.Setting and ParticipantsPatients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy.MethodsDelirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters).ResultsA total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2–2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1–1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6–1.2, P = .36; OR 1.1; CI 0.8–1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6–1.2, P = .27; OR 1.1, CI 0.8–1.4, P = .63).Conclusions and implicationsOur findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.     

Normal sperm parameters per se do not reliably account for fertility: A case–control study in the real-life setting

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.     

Conical Primary Cementless Stem in Revision Hip Arthroplasty: 94 Consecutive Implantations at a Mean Follow-Up of 12.7 years

BackgroundRevision of a failed total hip arthroplasty (THA) poses technical challenges. The use of primary stems for revision can be advantageous for maintaining bone stock and reducing complications: small case series have reported promising results in the short-term to mid-term follow-up. The aim of this study was to evaluate the long-term clinical and functional results and survivorship of a consecutive series of THA femoral component revisions using a conical primary cementless stem (PCS).MethodsNinety-four stem revisions with a preoperative Paprosky I or II defect were analyzed at an average follow-up of 12.7 ± 5.4 years. Aseptic loosening was the reason for revision in 92.5% of cases. Twenty patients were lost to follow-up. Two subgroups were created: Group 1 (n = 59) underwent isolated stem revision; Group 2 (n = 15) underwent complete THA revision. All were evaluated preoperatively and postoperatively based on the Harris Hip Score (HHS), the Western Ontario and McMaster Universities Index (WOMAC) score, and the visual analog scale for pain (VAS). Residual trochanteric pain and length discrepancies were recorded. Radiographic evaluation included signs of osteolysis, subsidence, loosening, and heterotopic ossification.ResultsPCS survivorship was 100% at 5 years and 95.9% at 10 years. Overall, significant postoperative improvements (P < .01) were observed on the HHS (44.3 vs 86.9), WOMAC (42.8 vs 82.8), and VAS (7.0 vs 3.0). Postoperative scores on all scales were higher for Group 1 (P < .01). Three patients (4.1%) underwent further stem revision. Demarcation lines (1 mm) were found in 12 (16.2%) patients and significant heterotopic ossifications in 22 (29.7%).ConclusionThe use of PCS for stem revision in failed THA with a limited femoral bone defect is a reliable option for both isolated stem revision and concomitant cup revision in well-selected patients.     

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.     

A capnography and transcutaneous CO2 profile of bariatric patients during early postoperative period after opioid-sparing anesthesia

BackgroundNoninvasive monitoring of partial pressure of carbon dioxide can be accomplished indirectly with capnography (P_ETCO₂) or with transcutaneous carbon dioxide monitoring (P_TCCO₂). The use of capnography has been shown to offer an advantage over pulse oximetry alone in the early detection of adverse respiratory events when supplemental oxygen is administered. Furthermore, capnography allows for the monitoring of various respiratory measures, including end-tidal carbon dioxide, respiratory rate, tidal volume, and changes in breathing patterns. Transcutaneous CO₂ also closely approximates arterial CO₂ values, but is not as easy to monitor for prolonged periods. The purpose of this study was to examine the usefulness of capnography and of transcutaneous carbon dioxide monitoring in patients recovering from obesity surgery at high risk of developing postoperative obstructive sleep apnea.MethodsIn a prospective observational study, 64 bariatric surgery patients at risk of developing obstructive sleep apnea were monitored in the postanesthesia care unit (PACU) with either capnography alone (31 patients) or capnography plus transcutaneous carbon dioxide monitoring (33 additional patients) every 3–5 minutes for the duration of their recovery. Primary endpoints included end-tidal and transcutaneous carbon dioxide, peripheral oxygen saturation, respiratory rate, pain scores, and incidence of adverse respiratory events.ResultsAlthough no adverse pulmonary events were observed, capnography detected several patients who experienced short periods of respiratory apnea while maintaining pulse oximetry readings within normal limits. Transcutaneous values were slow to change and averaged 4.5 ± 5.5 mm Hg (P < .05) higher than corresponding end-tidal measurements.ConclusionsThese results indicate the capabilities of both these noninvasive techniques for postoperative monitoring. Capnography acutely monitors changes in respiration, whereas transcutaneous monitoring more accurately reflects arterial CO₂ levels.     

Liver transplantation in a patient after COVID-19 – Rapid loss of antibodies and prolonged viral RNA shedding

To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA.