Opioid-Free Anesthesia for Open Radical Cystectomy Is Feasible and Accelerates Return of Bowel Function: A Matched Cohort Study.

The aim of this study was to evaluate the feasibility of opioid-free anesthesia (OFA) in open radical cystectomy (ORC) with urinary diversion and to assess the impact on recovery of gastrointestinal function. We hypothesized that OFA would lead to earlier recovery of bowel function. A total of 44 patients who underwent standardized ORC were divided into two groups (OFA group vs. control group). In both groups, patients received epidural analgesia (OFA group: bupivacaine 0.25%, control group: bupivacaine 0.1%, fentanyl 2 mcg/mL, and epinephrine 2 mcg/mL). The primary endpoint was time to first defecation. Secondary endpoints were incidence of postoperative ileus (POI) and incidence of postoperative nausea and vomiting (PONV). The median time to first defecation was 62.5 h [45.8-80.8] in the OFA group and 118.5 h [82.6-142.3] (p < 0.001) in the control group. With regard to POI (OFA group: 1/22 patients (4.5%); control group: 2/22 (9.1%)) and PONV (OFA group: 5/22 patients (22.7%); control group: 10/22 (45.5%)), trends but no significant results were found (p = 0.99 and p = 0.203, respectively). OFA appears to be feasible in ORC and to improve postoperative functional gastrointestinal recovery by halving the time to first defecation compared with standard fentanyl-based intraoperative anesthesia

Frequent Infection of Cerebellar Granule Cell Neurons by Polyomavirus JC in Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) occurs most often in immunosuppressed individuals. The lesions of PML result from astrocyte and oligodendrocyte infection by the polyomavirus JC (JCV); JCV has also been shown to infect and destroy cerebellar granule cell neurons (GCNs) in 2 HIV-positive patients. To determine the prevalence and pattern of JCV infection in GCNs we immunostained formalin-fixed, paraffin-embedded cerebellar samples from 40 HIV-positive and 3 HIV-negative PML patients for JCV, glial and neuronal markers. JCV infection was detected in 30 patients (70%); 28 (93%) of these had JCV-infected cells in the granule cell layer (GCL); JCV-infected GCNs were demonstrated in 15/19 (79%) tested cases. JCV regulatory T antigen (T Ag) was expressed more frequently and abundantly in GCNs than JCV VP1 capsid protein. None of 37 HIV-negative controls but 1/35 (3%) HIV-positive subjects without PML had distinct foci of JCV-infected GCNs. Thus, JCV infection of GCNs is frequent in PML patients and may occur in the absence of cerebellar white matter demyelinating lesions. The predominance of T Ag over VP1 expression in GCNs suggests that they may be the site of early or latent central nervous system JCV infection. These results indicate that infection of GCNs is an important, previously overlooked aspect of JCV pathogenesis in immunosuppressed individuals

Report on the key comparison, CCM.F-K23 in force at 200 N and 500 N

The working group force of the CCM decided to make a comparison at 200 N and 500 N at the meeting held in Kajaani in November 2014. At the meeting held in Braunschweig in June 2017 it was decided that METAS would be the pilot of this comparison. The working group agreed that the transfer standard would be independently organized by each participating laboratory according to the principle "bring your own device". This solution would reduce the work needed by the pilot and would allow for a faster conclusion of the comparison. The participants have been chosen according to their actual CMC and to the expected uncertainty of their reference system

Plasma disappearance rate of albumin when infused as a 20% solution.

BACKGROUND The transcapillary leakage of albumin is increased by inflammation and major surgery, but whether exogenous albumin also disappears faster is unclear. METHODS An intravenous infusion of 3 mL/kg of 20% albumin was given over 30 min to 70 subjects consisting of 15 healthy volunteers, 15 post-burn patients, 15 patients who underwent surgery with minor bleeding, 10 who underwent surgery with major bleeding (mean, 1.1 L) and 15 postoperative patients. Blood Hb and plasma albumin were measured on 15 occasions over 5 h. The rate of albumin disappearance from the plasma was quantitated with population kinetic methodology and reported as the half-life (T1/2). RESULTS No differences were observed for T1/2 between volunteers, post-burn patients, patients who underwent surgery with minor bleeding and postoperative patients. The T1/2 averaged 16.2 h, which corresponds to 3.8% of the amount infused per h. Two groups showed plasma concentrations of C-reactive protein of approximately 60 mg/L and still had a similarly long T1/2 for albumin. By contrast, patients undergoing surgery associated with major hemorrhage had a shorter T1/2, corresponding to 15% of the infused albumin per h. In addition, our analyses show that the T1/2 differ greatly depending on whether the calculations consider plasma volume changes and blood losses. CONCLUSION The disappearance rate of the albumin in 20% preparations was low in volunteers, in patients with moderately severe inflammation, and in postoperative patients

Frequent Infection of Neurons by SV40 Virus in SIV-Infected Macaque Monkeys with Progressive Multifocal Leukoencephalopathy and Meningoencephalitis

Simian virus 40 (SV40), family Polyomaviridae, in immunocompromised macaques can cause fatal demyelinating central nervous system disease analogous to progressive multifocal leukoencephalopathy caused by John Cunningham (JC) virus in immunocompromised humans. Recently, we have demonstrated that JC virus can infect cerebellar granule cell neurons and cortical pyramidal neurons in immunosuppressed people. To examine whether SV40 neuronal infection occurs spontaneously in immunosuppressed macaques, we analyzed archival brain specimens from 20 simian immunodeficiency virus–infected rhesus with AIDS and 1 cynomolgus post-transplant selected with SV40 brain infection from archival records from 1991 to 2012. In addition to white matter SV40 distribution in classic demyelinating progressive multifocal leukoencephalopathy, some of the 21 monkeys exhibited meningeal, subpial neocortical, and periventricular virus. This distribution pattern corresponded to broader viral tropism with neuronal infection in 14 (66.7%) of 21 cases. In all 14 cases, identified neurons were positive for early SV40 transcript large T antigen, but only 4 of the 14 cases exhibited late viral transcript viral protein 1–positive neurons. SV40-infected neurons were detected in frontal, parietal, occipital, and temporal cortices, hippocampus, thalamus, and brain stem. These observations confirm that spontaneous SV40 neuronal infection occurs in immunosuppressed macaques, which parallels JC virus–neuronal infection in immunosuppressed patients. Neuronal infection may be an important aspect of both SV40 and JC virus neuropathogenesis in their respective hosts

Processing and properties of thin film pyroelectric devices

Pyroelectric PbTiO3 thin films devices with two temperature compensating elements on a SiO2/Si3N4 membranes have been fabricated and characterized. The measured voltage responsivity as a function of radiation modulation frequency has been compared to finite element model calculation. The relevant film properties have been compared for sputter and a sol-gel deposition techniques. The calculated responsivity amounts to 30 V/W. The measured pyroelectric signal is a few mu V

Structure and dynamics of the deoxyguanosine-sensing riboswitch studied by NMR-spectroscopy

The mfl-riboswitch regulates expression of ribonucleotide reductase subunit in Mesoplasma florum by binding to 2′-deoxyguanosine and thereby promoting transcription termination. We characterized the structure of the ligand-bound aptamer domain by NMR spectroscopy and compared the mfl-aptamer to the aptamer domain of the closely related purine-sensing riboswitches. We show that the mfl-aptamer accommodates the extra 2′-deoxyribose unit of the ligand by forming a more relaxed binding pocket than these found in the purine-sensing riboswitches. Tertiary structures of the xpt-aptamer bound to guanine and of the mfl-aptamer bound to 2′-deoxyguanosine exhibit very similar features, although the sequence of the mfl-aptamer contains several alterations compared to the purine-aptamer consensus sequence. These alterations include the truncation of a hairpin loop which is crucial for complex formation in all purine-sensing riboswitches characterized to date. We further defined structural features and ligand binding requirements of the free mfl-aptamer and found that the presence of Mg2+ is not essential for complex formation, but facilitates ligand binding by promoting pre-organization of key structural motifs in the free aptamer

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Comment on Crettenand et al. Is Continuous Wound Infiltration a Better Option for Postoperative Pain Management after Open Nephrectomy Compared to Thoracic Epidural Analgesia? <i>J. Clin. Med.</i> 2023, <i>12</i>, 2974

We have read with great interest the retrospective study recently published by Crettenand et al. in this journal [...

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION ClinicalTrials.gov NCT05391607, date of registration May 26, 2022