The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses.

The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly to treat prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and infection in both TMPRSS2- and nonexpressing immortalized cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E- and OC43-infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72 h postinfection. The virus-mediated effect on AR-signaling was further confirmed with a consensus androgen response element-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase-reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen-signaling, offering insights for disparities in viral outcomes and antiviral interventions.

Effect of Photoinitiators Doped in PDMS for Femtosecond-Laser Writing: Characterization and Outcomes.

Herein, we have characterized in depth the effect of femtosecond (fs)-laser writing on various polydimethylsiloxane (PDMS)-based composites. The study combines systematic and nanoscale characterizations for the PDMS blends that include various photoinitiators (organic and inorganic agents) before and after fs-laser writing. The results exhibit that the photoinitiators can dictate the mechanical properties of the PDMS, in which Young's modulus of PDMS composites has higher elasticity. The study illustrates a major improvement in refractive index change by 15 times higher in the case of PDMS/BP-Ge [benzophenone (BP) allytriethylgermane] and Irgacure 184. Additional enhancement was achieved in the optical performance levels of the PDMS composites (the PDMS composites of Irgacure 184/500, BP-Ge, and Ge-ATEG have a relative difference of less than 5% in comparison with pristine PDMS), which are on par with glasses. This insightful study can guide future investigators in choosing photoinitiators for particular applications in photonics and polymer chemistry.

Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children.

BACKGROUND: Elevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism. METHODS: Diffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6-11 years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis. RESULTS: Results revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections. LIMITATIONS: All participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum. CONCLUSIONS: These findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations.

Photosensitization agents for fs laser writing in PDMS.

This study aims at identifying compounds incorporated into Polydimethylsiloxane (PDMS) which produce large refractive index change under fs laser exposition, potentially leading to optimal writing of waveguides or photonic devices in such a soft host. Germanium derivative, titania and zirconite derivatives, benzophenone (Bp), irgacure-184/500/1173 and 2959 are investigated. We show a mapping of the RI index change relative to the writing speed (1 to 40 mm/s), the repetition rate (606 to 101 kHz) and the number of passes (1 to 8) from which we establish quantitative parameters to allow the comparison between samples. We show that the organic materials, especially irgacure-184 and benzophenone yield a significantly higher maximum refractive index change in the order of 10-2. We also show that the strongest photosensitivity is achieved with a mixture of organic/organo-metallic material of Bp + Ge. We report a synergetic effect on photosensitivity of this novel mixture.

Synthesis of core-shell magnetic molecularly imprinted polymer for the selective determination of imidacloprid in apple samples.

This work demonstrates the synthesis and characterization of core-shell magnetic molecularly imprinted polymers based on surface imprinting using methacryloyl chloride as a functional monomer for the selective extraction of imidacloprid (template) from apple fruit. The characterization analysis results ensured the successful synthesis of the magnetic molecularly imprinted polymers owing to their heterogeneous structure and good magnetic properties. An isothermal binding test was assessed with a pseudo-second-order kinetic model, and the kinetic results fit well to the Freundlich isothermal model. The polymers exhibited an adsorption capacity of 5.75 mg/g for the target analyte with a good selective extraction ability. In addition, the polymers can be reused several times without significant performance loss. The molecularly imprinted polymers showed good performance in the analysis of spiked apple sample with a linear range of 0.05-1.0 mg/L, a limit of detection of 0.048 mg/L and a limit of quantification of 0.146 mg/L (S/N = 3/10). The recoveries of the samples were 77.66-96.57% and their respective relative standard deviations were 3.36-0.45%. All the results indicated that the proposed method provided good selective extraction, as qualifying the analytical standards.

Portal Hypertension: An Underestimated Entity?

OBJECTIVE: The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures. BACKGROUND: Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension. METHODS: From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (≤15 vs >15) and compared with NEV patients. RESULTS: One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients. CONCLUSIONS: Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.

Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer.

The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans-encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans-heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6±3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2.5 (DQB1*02, DQA1*05), DQ2.3 (DQB1*02, DQA1*03), and DQ4.3 (DQB1*04, DQA1*03). Two of them eventually lost grafts (2 and 5years later) with allograft nephropathy. In conclusion, post-transplant patients may develop DSA to donor DQ trans-heterodimers. Further studies are warranted to determine the clinical significance of such DSAs.

Prolonged pentobarbital-induced coma for the treatment of severe seizures related to posterior reversible encephalopathy syndrome.

In this report, we describe a case of posterior reversible encephalopathy syndrome in a female patient after deceased donor liver transplantation. She developed posterior reversible encephalopathy syndrome on postoperative day 3 and did not improve despite adjustments in immunosuppressive therapy. The patient had symptoms of severe brain edema requiring maximal therapy, which included cooling, mannitol, 3% saline, and a pentobarbital infusion. Attempts to lighten the level of sedation failed because of recurring intractable seizure activity. Reductions in therapeutic support were ultimately successful after 62 days of continuous pentobarbital therapy. The patient awoke neurologically intact and was discharged to a rehabilitation center in good condition.

Use of methylene blue for treatment of severe sepsis in an immunosuppressed patient after liver transplantation.

Sepsis in the immunosuppressed patient is associated with very high mortality and morbidity. Treatment of sepsis in immunocompromised patients is especially challenging due to an unbalanced systemic inflammatory reaction with subsequent development of profound vasoplegia. Methylene blue (MB) has been successfully used for the treatment of refractory hypotension, but its use has not previously been reported for treatment of sepsis in immunosuppressed patients. The mechanism of MB's action is thought to be due to its inhibitory effect on cGMP-mediated vasodilatation. This case report describes the successful use of MB for treatment of severe septic shock in an immunosuppressed patient after liver transplantation. Hypotension in this patient was refractory to volume repletion and a combination of vasopressors. After MB administration, hemodynamic stability was rapidly reestablished. In the setting of severe sepsis in an immunosuppressed patient, MB should be considered early as a therapeutic option for treatment of refractory vasoplegia.

Pancreaticoduodenectomy for periampullary malignancies: the effect of bile colonization on the postoperative outcome.

OBJECTIVES: The presence of bacteria in the bile of patients undergoing biliary tract surgery has been proposed as associated to an increased incidence of postoperative complications. The present study was designed to determine whether colonization of the bile has an adverse effect in terms of postoperative infectious or noninfectious complications and mortality in a homogenous population of patients suffering from periampullary region malignancies, who all underwent resectional (curative) procedures. MATERIALS AND METHODS: Between January 1997 and December 2002, 115 patients (n = 115) suffering from periampullary region malignancies underwent resectional procedures. Fifty-two of the above patients were referred having undergone preoperative internal biliary drainage. During the operation, bile was routinely isolated from the common bile duct and was sent for culture and sensitivity. Based on the bile culture results, the patients were divided in sterile and colonized group and were retrospectively compared in terms of postoperative outcome and mortality. RESULTS: Of the 115 bile cultures, 67 were colonized with bacteria and 48 were sterile. Postoperatively, 40 patients developed 35 noninfectious and 21 infectious complications. Univariate analysis did not disclose statistically significant differences in overall, noninfectious or infectious morbidity and mortality between the two groups of patients. Although not statistically significant, a higher incidence (22 vs 10%) of postoperative leaks in the colonized group of patients was noticed. Multiple regression analysis disclosed that colonized bile was independently related to the advanced age, preoperative biliary drainage presence, elevated preoperative serum bilirubin levels and low preoperative serum albumin levels but did not predispose to an increased postoperative morbidity, mortality, or reoperation rate. CONCLUSION: The present study did not conclude in any statistically significant differences in the postoperative infectious and noninfectious morbidity as well as mortality, between colonized and sterile groups of patients who underwent resectional procedures for malignancies of the periampullary region. Although internal biliary drainage introduces microorganisms into the biliary tree, this colonization does not increase the risk of either infectious or noninfectious complications or postoperative death. Thus, the likelihood of bacterobilia should not contraindicate the procedure in selected cases.

Two cases of ectopic liver attached to the gallbladder wall.

BACKGROUND: Ectopic liver tissue is occasionally found either attached to the gallbladder or elsewhere in the upper abdomen. CASE OUTLINES: A 49-year-old man and a 39-year-old woman were found to have a tongue of liver tissue attached to the serosa of the gallbladder (but separate from the liver) during laparoscopic cholecystectomy for gallstones. The ectopic liver was removed with the gallbladder and was histologically normal in each case. DISCUSSION: Several embryological hypotheses have been advanced to explain the development of ectopic liver. The anomaly is usually discovered incidentally at operation. Although the tissue is histologically normal.it can develop the same conditions as orthotopic liver.