Genomic reconstruction of short-chain fatty acid production by the human gut microbiota.

Short-chain fatty acids (SCFAs) including acetate, formate, propionate, and butyrate are the end products of dietary fiber and host glycan fermentation by the human gut microbiota (HGM). SCFAs produced in the column are of utmost importance for host physiology and health. Butyrate and propionate improve gut health and play a key role in the neuroendocrine and immune systems. Prediction of HGM metabolic potential is important for understanding the influence of diet and HGM-produced metabolites on human health. We conducted a detailed metabolic reconstruction of pathways for the synthesis of SCFAs and L- and D-lactate, as additional fermentation products, in a reference set of 2,856 bacterial genomes representing strains of >800 known HGM species. The reconstructed butyrate and propionate pathways included four and three pathway variants, respectively, that start from different metabolic precursors. Altogether, we identified 48 metabolic enzymes, including five alternative enzymes in propionate pathways, and propagated their occurrences across all studied genomes. We established genomic signatures for reconstructed pathways and classified genomes according to their simplified binary phenotypes encoding the ability ("1") or inability ("0") of a given organism to produce SCFAs. The resulting binary phenotypes combined into a binary phenotype matrix were used to assess the SCFA synthesis potential of HGM samples from several public metagenomic studies. We report baseline and variance for Community Phenotype Indices calculated for SCFAs production capabilities in 16S metagenomic samples of intestinal microbiota from two large national cohorts (American Gut Project, UK twins), the Hadza hunter-gatherers, and the young children cohort of infants with high-risk for type 1 diabetes. We further linked the predicted SCFA metabolic capabilities with available SCFA concentrations both for in vivo fecal samples and in vitro fermentation samples from previous studies. Finally, we analyzed differential representation of individual SCFA pathway genes across several WGS metagenomic datasets. The obtained collection of SCFA pathway genes and phenotypes enables the predictive metabolic phenotype profiling of HGM datasets and enhances the in silico methodology to study cross-feeding interactions in the gut microbiomes.

SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases.

The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.

Initial multi-target approach shows importance of improved caprine arthritis-encephalitis virus control program in Russia for hobbyist goat farms.

BACKGROUND AND AIM: Several reports described the detection of specific caprine arthritis-encephalitis virus (CAEV) antibodies in Russian goat populations, which indicates the circulation of CAEV in Russian goat farms. The aim of this study was to use a multi-target approach to testing with both serological tests and an in-house real-time (RT) molecular test to investigate the prevalence of CAEV in goats from three hobbyist farms in the Republic of Tatarstan, Russia. MATERIALS AND METHODS: We applied a multi-target approach to testing with both enzyme-linked immunosorbent assay (ELISA) and an in-house RT polymerase chain reaction test to investigate the prevalence of CAEV in goats. Animals from the three hobbyist farms were used in this study. The animals from two farms (n=13 for F1 and n=8 for F2) had clinical signs of arthritis and mastitis. In the third farm (n=15 for F3), all goats were home-bred and had no contact with imported animals. RESULTS: CAEV antibodies (ELISA targets TM env and gag genes) were detected in serum samples from two farms (F1 and F2), indicating seroprevalence of 87.50-92.31%. Specific CAEV antibodies were also detected in milk samples. CAEV proviral DNA was detected in 53.85-62.50%. The results from all tests performed in the third farm (F3) were negative, indicating that all tests were 100% specific. CONCLUSION: The results showed that CAEV is circulating and present in small hobbyist goat farms in Russia. Serological and molecular tests could be important for programs to control and eradicate CAEV in Russia for hobbyist goat farms.

Percutaneous nephrolithotomy for staghorn calculi: Troubleshooting and managing complications.

Staghorn calculi comprise a unique subset of complex kidney stone disease. Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for staghorn stones. Despite continuous refinements to the technique and instrumentation of PCNL, these stones remain a troublesome challenge for endourologists and are associated with a higher rate of perioperative complications than that for non-staghorn stones. Common and notable intraoperative complications include bleeding, renal collecting system injury, injury of visceral organs, pulmonary complications, thromboembolic complications, extrarenal stone migration, and misplacement of the nephrostomy tube. Postoperative complications include infection and urosepsis, bleeding, persistent nephrocutaneous urine leakage, infundibular stenosis, and death. In this review, we report recommendations regarding troubleshooting measures that can be used to identify and characterize these complications. Additionally, we include information regarding management strategies for complications associated with PCNL for staghorn calculi.

Comparison of silicone versus polyurethane ureteral stents: a prospective controlled study.

BACKGROUND: Approximately 80% of patients with indwelling ureteral stents experience stent related symptoms (SRS). We believe SRS can be reduced through altering the composition of ureteral stents to a less firm material. Therefore, we aim to compare modern silicone and polyurethane ureteral stents in terms of SRS intensity and safety. METHODS: From June 2018 to October 2018, patients from two distinct clinical centers were prospectively enrolled in the study and stratified (non-randomly) into either control group A, patients who received polyurethane stents (Rüsch, Teleflex), or experimental group B, patients who received silicone stents (Cook Medical). Each participant completed a survey 1 h after stent insertion, in the middle of the stent dwelling period, and before stent removal or ureteroscopy noting body pain and overactive bladder via the visual analog scale pain (VASP) and overactive bladder (OAB) awareness tool, respectively. Additionally, successfulness of stent placement, hematuria, number of unplanned visits, and stent encrustation rates were assessed within each group. RESULTS: A total of 50 patients participated in the study, control group A consisted of 20 patients and experimental group B consisted of 30 patients. Participants in group B, silicone ureteral stents, demonstrated significantly lower mean values of VASP 2 weeks prior to stent removal and promptly before stent removal (p = 0.023 and p = 0.014, respectively). No other comparisons between the two groups were statistically significant. CONCLUSIONS: Compared to polyurethane ureteral stents, silicone ureteral stents are associated with lower body pain intensity assessed by VASP 2 weeks before stent removal and at the time of stent removal. TRIAL REGISTRATION: Current Controlled Trials NCT04000178. Retrospectively registered on June 26, 2019.

Reducing kidney motion: optimizing anesthesia and combining respiratory support for retrograde intrarenal surgery: a pilot study.

BACKGROUND: One of the greatest challenges presented with RIRS is the potential for movement of the stone within the operative field associated with diaphragm and chest respiratory excursions due to mechanical ventilation. To overcome this challenge, we propose in this pilot study a new general anesthesia technique combining high frequency jet ventilation (HFJV) with small volume mechanical ventilation (SVMV). Data regarding safety, feasibility and surgeons' impression was assessed. METHODS: Patients undergoing RIRS for kidney stones from November 2017 to May 2018 were prospectively recruited to participate in the study. In each case after the beginning of general anesthesia (GA) with mechanical ventilation (MV) surgeons were asked to assess the mobility of the operative field and conditions for laser lithotripsy according to the developed questionnaire scale. The questionnaire consisted of 5 degrees of assessment of kidney mobility and each question was scored from 1 to 5, 1 being very mobile (extremely poor conditions for dusting) and 5 completely immobile (Ideal conditions for dusting). After the assessment GA was modified with combined respiratory support (CRS), reducing tidal volume and respiratory rate (small volume mechanical ventilation, SVMV) and applying in the same time transcatheter high frequency jet ventilation (HFJV) inside the closed circuit. After beginning of CRS, surgeons were once again asked to assess the mobility of the operative field and the conditions for laser lithotripsy. Main ventilation parameters were recorded and compared in both regimens. RESULTS: A total of 38 patients were included in the study. The mean age was 49 (range 45-53) with a mean stone size of 10 mm (range 10-14) and Hounsfield unit of 1060 (range 930-1190). All patients underwent successful RIRS and no intraoperative complications occurred throughout the duration of the study. A statistically significant difference between ventilation parameters prior to and after CRS institution was detected in all cases, however their clinical impact was negligible. Despite this, assessment via the questionnaire scale point values varied significantly before and after the application of CRS and were 2.3 (2.1; 2.6) and 3.8 (3.7; 4.0) respectively (p < 0.001). CONCLUSIONS: The novel combined respiratory approach consisting of HFJV and SVMV appears to provide better conditions for stone dusting through reduced respiratory kidney motion and is not associated with adverse health effects or complications. TRIAL REGISTRATION: NCT03999255 , date of registration: 25th June 2019 (retrospectively registered).

Combination of M2e peptide with stalk HA epitopes of influenza A virus enhances protective properties of recombinant vaccine.

BACKGROUND: Influenza infection could be more effectively controlled if a multi-purpose vaccine with the ability to induce responses against most, or all, influenza A subtypes could be generated. Conserved viral proteins are a promising basis for the creation of a broadly protective vaccine. In the present study, the immunogenicity and protective properties of three recombinant proteins (vaccine candidates), comprising conserved viral proteins fused with bacterial flagellin, were compared. METHODS: Balb/c mice were immunized intranasally with recombinant proteins comprising either one viral protein (the ectodomain of the M2 protein, 'M2e') or two viral proteins (M2e and the hemagglutinin second subunit 'HA2' epitope) genetically fused with flagellin. Further, two different consensus variants of HA2 were used. Therefore, three experimental positives were used in addition to the negative control (Flg-his). The mucosal, humoral, and T-cell immune responses to these constructs were evaluated. RESULT: We have demonstrated that insertion of the HA2 consensus polypeptide (aa 76-130), derived from either the first (HA2-1) or second (HA2-2) virus phylogenetic group, into the recombinant Flg4M2e protein significantly enhanced its immunogenicity and protective properties. Intranasal administration of the vaccine candidates (Flg-HA2-2-4M2e or Flg-HA2-1-4M2e) induced considerable mucosal and systemic responses directed at both the M2e-protein and, in general, the influenza A virus. However, the immune response elicited by the Flg-HA2-1-4M2e protein was weaker than the one generated by Flg-HA2-2-4M2e. These recombinant proteins containing both viral peptides provide complete protection from lethal challenge with various influenza viruses: A/H3N2; A/H2N2; and A/H5N1. CONCLUSION: This study demonstrates that the intranasal administration of Flg-HA2-2-4M2e recombinant protein induces a strong immune response which provides broad protection against various influenza viruses. This construct is therefore a strong candidate for development as a universal vaccine.

Novel Approach for Endoscopic Management of Duodenal Injury during Perirenal Infected Haematoma Drainage after Shock-Wave Lithotripsy.

Background. Gaining percutaneous access during percutaneous nephrolithotomy (PNL) can be complicated with the bowel injury. We report a novel approach of management of duodenal injury complicating percutaneous drainage of infected haematoma after Shock-Wave Lithotripsy (SWL). Case Presentation. A 57-year-old patient with the 15 mm right pelvic kidney stone underwent uneventful SWL. Patient visited emergency department 3 days later with high fever and chills with severe right flank pain. CT urography revealed lower pole kidney injury with signs of infected hematoma due to low attenuation areas but without signs of obstruction or urine leakage. Infected haematoma was drained percutaneously under ultrasound and X-ray control and a pigtail catheter 10 Fr was left beneath the lower pole of the right kidney. Postoperatively duodenal injury was suspected due to amber color, low creatinine, and high bilirubin level in the drainage output. CT demonstrated that the pigtail of the drain had entered the second part of the duodenum. Catheter was withdrawn and defect of the duodenal wall was stapled with four staples endoscopically. After 2 days of fasting patient was allowed to start oral food intake and was discharged on the 5th day. Conclusion. Injury of the duodenum during percutaneous kidney manipulation is an extremely rare complication. Conservative management consisting of endoscopic stapling of the duodenal wall defect is a safe and feasible approach to expediting the recovery of the patient.

"Valve"-Type Retainment of Flexible Ureteroscope in the Distal Ureter.

Introduction: Flexible ureteroscopy (fURS) is an endoscopic procedure for the minimally invasive treatment of ureteral and renal calculi. Due to improvements in technique and ureteroscopic instrumentation over the past two decades, complications associated with URS are infrequent. However, in the event of an unexpected device malfunction or failure, the operating surgeon must employ prompt, resolute decision-making to resolve any intraoperative complications and avoid significant injury to the kidney or ureter. Case Presentation: The patient was a 53-year-old male with a 7 mm left upper pole renal stone managed by fURS and laser lithotripsy. A ureteral access sheath (UAS) was not deployed during the procedure. During fragmentation of the stone, we were unexpectedly unable to retract the ureteroscope from the ureter. Herein, we describe the procedural details leading up to the complication and the careful maneuvering required to remove the ureteroscope without damaging the ureter or the instrument. Conclusions: We recommend use of a UAS during fURS for the treatment of ureteral and renal calculi, if not using ureter access sheath, not advancing the ureteroscope above the stone, leaving it behind the tip of the instrument, while in the ureter. Utilization of a ureter access sheath could have possibly avoided this kind of complication.

Evaluation of the effect of Bernoulli maneuver on operative time during mini-percutaneous nephrolithotomy: A prospective randomized study.

PURPOSE: To evaluate the effect of 'Bernoulli maneuver' (bringing the access sheath to horizontal plane) on operative time and stone free rates in patients undergoing mini-percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: All consecutive patients with a solitary kidney stone undergoing a mini-PCNL between 2015 and 2016 were included into this study. Patients were randomized either to standard prone or control (C) group patients or to tilted prone with 'Bernoulli maneuver' group (B) patients. Pre-, intra-, and postoperative characteristics of these 2 groups were recorded and analyzed. RESULTS: A total of 67 patients were included in the study. Of these, 40 patients were randomized to group C and 27 to group B. The mean (95% confidence limits) stone size (mm) in group C and B was 14 (13, 15) and 13 (11, 14), respectively (p=0.26). Nephroscopy time was shorter in Bernoulli group (35 minutes vs. 23 minutes, p=1.5·10-5, and Bayes factor BF10=2,340, and Cohen standardized effect size dst=1.2). The difference made it up 12 minutes (with 95% confidence interval from 8 to 18 minutes). There were no statistically significant differences between groups regarding white blood cell, creatinine level and stone-free status defined by computed tomography on the first postoperative day. CONCLUSIONS: In our study the 'Bernoulli maneuver' led to a shorter nephroscopy time in mini-PCNL. This maneuver can significantly reduce nephroscopy time and save significant amount of operative time, especially in tertiary referral centers with high-volume mini-PCNL procedures.

Ultrasound-Guided Ureteral Stent Removal in Women.

OBJECTIVES: The purpose of this study was to develop a fast, comfortable, and safe method of ureteral stent removal in women. METHODS: From February 2014 to July 2015, a retrospective multicenter controlled study including 82 female outpatients was conducted. The control group was composed of 46 patients who underwent stent removal using a 22F cystoscope. The experimental group was composed of 36 patients who underwent stent removal under ultrasound guidance with a 15F spiral-ending device. Exclusion criteria were pelvic organ prolapse quantification stage II or higher and complicated stents (with migration or encrustation). RESULTS: All studied patients had successful ureteral stent removal. No complications were seen in both groups. Differences between mean visual analog pain scale scores and stent removal durations were statistically significant in favor of the experimental group (P = .0077 and .0075, respectively). CONCLUSIONS: The proposed method for ureteral stent removal in women under ultrasound guidance was shown to be faster and to have lower visual analog pain scale scores, in comparison with removal by a cystoscope, which makes it an attractive option for outpatient urologic praxis in uncomplicated cases, and because it is free of the risk of ionizing radiation and more comfortable, it can be used in pregnant patients.

Sculpturing in urology, or how to make percutaneous nephrolithotomy easier.

PURPOSE: To investigate the usefulness of Plasticine biomodeling in surgical percutaneous management of complex renal stone. PATIENTS AND METHODS: A total of 32 patients with complex renal stones (complete staghorn stones or partial staghorn stone with multiple caliceal stones) were included in this study from 2012 to 2013. Computed tomography (CT) urography with three-dimensional (3D) reconstructions was used as standard preoperative imaging in all patients. Preoperatively, Plasticine replication of the pelvicaliceal system was performed by the operating surgeon, based on the gathered 3D reconstructions. Then the model was taken to the operating room and used as a reference model in a sterile polyethylene bag during the operation. RESULTS: Percutaneous renal access was achieved successfully in all cases. Twenty-nine (91%) patients were treated in the prone position and only 3 (9%) in supine position. There were 18 (56%) patients who had a single tract, 9 (28%) patients had two tracts, 3 (9%) patients had three tracts, and one (3%) patient needed four tracts. The mean operative time was 92 (±26) minutes. Second-look percutaneous nephrolithotomy (PCNL) was needed in 9 of 32 (28%) patients. All second-look sessions were performed in 2 to 3 days and/or on a normalized temperature. Six of 11 (54.5%) patients with complete staghorn stones needed a second-look PCNL session. Complete stone clearance was confirmed by low-dose CT, performed at 24 hours after surgery, in 89.4% of the patients treated by a single PCNL session and 82% in those who needed second-look sessions. The overall stone-free rate (SFR) in the study after second looks was 87.3%. CONCLUSIONS: The proposed Plasticine 3D model seems to provide better preoperative renal collecting system appreciation and to serve as a reference tool during the operation, which in turn might increase SFRs and lower the complications rate after PCNL.