Prevention of encephalomyocarditis virus-induced diabetes by live recombinant Mycobacterium bovis bacillus Calmette-Guérin in susceptible mice

The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in susceptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering the major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycobacterium bovis bacillus Calmette-Guerin (BCG). None of the SJL/J mice immunized with live recombinant BCG-VP1 (rBCG-VP1) became diabetic when challenged with the highly diabetogenic EMC-D virus, but the control mice inoculated with normal BCG developed diabetes during the same challenge. VP1-specific antibodies (including neutralizing antibodies) were markedly increased over time and reached the maximum titer at week 10 after a single immunization. The plateau of the titer lasted longer than 4 weeks. Mice and guinea pigs immunized with live rBCG-VP1 showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus. The preventive immunity still worked effectively 10 months after the primary immunization. At that time, the VP1-specific antibody was almost undetectable in the bloodstream, but a large number of VP1-specific lymphocytes was found in the spleen of the immunized mice. Our results show that live rBCG-VP1 elicits effective humoral and long-lasting cellular immune responses against EMC-D virus infection that results in the prevention of virus-induced diabetes in susceptible mice.     

Antimicrobial mesh versus vaginal wall sling: a comparative outcomes analysis

PURPOSE: We prospectively compared transvaginal antimicrobial mesh (MycroMesh*) and anterior vaginal wall slings using an outcomes analysis. MATERIALS AND METHODS: Between August 1997 and November 1998 we implanted transvaginal slings in 40 consecutive women randomized to a synthetic mesh (20) or vaginal wall (20) group. All patients had documented stress urinary incontinence on preoperative urodynamics. We prospectively compared postoperative outcomes data obtained from pelvic examinations, cough stress test, cotton swab test and validated patient questionnaires using a visual analog scale. RESULTS: Complete followup was available in all patients. Mean followup was 22 months (range 12 to 27). Stress incontinence was cured in 95% of the mesh and 70% of the vaginal wall group, and pelvic prolapse was cured in 100% and 95%, respectively. Transient de novo urge incontinence was noted in 12.5% of the mesh and 14.3% of the vaginal wall group. Mean postoperative cotton swab angle during Valsalva's maneuver was 20 and 45 degrees for the mesh and vaginal wall groups, respectively. The incidence of urinary retention and tissue erosion was 0% for both groups. The satisfaction rate was 100% and 80% for the mesh and vaginal wall groups, respectively. CONCLUSIONS: The antimicrobial MycroMesh sling was superior to the vaginal wall sling for correction of stress incontinence and pelvic prolapse with comparatively low morbidity.     

Acupuncture stimulation for motor cortex activities: a 3T fMRI study

The acupoint, GB34, located in the back of the knee, is known to be effective in recovering motor function after a stroke. This study uses a functional magnetic resonance imaging (fMRI) study with 3T scanner to investigate whether or not acupuncture of GB34 produces a significant response of the modulation of somatomotor areas. A fMRI of the whole brain was performed in ten normal healthy subjects during two task stimulations of acupuncture manipulation on GB34 and sham points, inserting and twisting the needle for 25 seconds at a rate of approximately 120 times per minute; the needle manipulation was paused for a duration of 25 seconds as a control state. The process was repeated four times to have four epochs of stimulation. Bilateral sensorimotor areas (BA 3, 4, 6 and 7) showed approximately 6% of stimulation-related BOLD signal contrast, whereas very few areas were activated when sham stimulation was given. Acupuncture stimulation in GB34 modulates the cortical activities of the somatomotor area in humans. The present findings may shed light on the CNS mechanism of motor function by acupuncture, and form a basis for future investigations of motor modulation circuits in stroke patients.     

Correlation between intraocular pressure, central corneal thickness, stage of glaucoma, and demographic patient data: prospective analysis of biophysical parameters in tertiary glaucoma practice populations

PURPOSE: To determine the correlation of central corneal thickness (CCT) to Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT, PASCAL), and to glaucoma stage as assessed by cup-to-disc ratio (CDR). DESIGN: Prospective, cross-sectional tricenter observation study. PATIENTS AND METHODS: From three glaucoma specialty practices a sample of 406 independent eyes was included. After ultrasound pachymetry, intraocular pressure was measured using PASCAL and Goldmann applanation tonometry and cup-to-disc ration was reassessed. Demographic data were included in the multivariate analysis. RESULTS: Mean corneal thickness was 540 microm. African Americans and normal-tension glaucoma patients showed the lowest values (518 microm and 522 microm, respectively). These values were significantly thinner than the central corneal thickness of Caucasians (549 microm) and ocular hypertensives (564 microm). Intraocular pressure assessed by Goldmann applanation tonometry shows a significant correlation with central corneal thickness (r = 0.068, P < 0.001), whereas PASCAL is not significantly associated with central corneal thickness (r < 0.001, P = 0.997). Increased IOP is significantly correlated with large ocular pulse amplitudes (r = 0.13, P < 0.001), which is predominantly seen in ocular hypertensives. A significant negative correlation was detected between cup-to-disc ratio and central corneal thickness (r = 0.102, P < 0.001). CONCLUSION: Glaucoma patients with thin central corneal thickness are more likely to be found at an advanced stage of the disease and among those with normal-tension glaucoma and black African ancestry. Underestimation of intraocular pressure by Goldmann applanation tonometry could be one causative factor.     

Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.     

Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.     

Effective drug delivery by PEGylated drug conjugates

The current review presents an update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG drug conjugates, initiated by the use of higher molecular weight PEGs (M(w)>20,000), especially 40,000 which is estimated to have a plasma circulating t(1/2) of approximately 10 h in mice. This recent resuscitation of small organic molecule delivery by high molecular weight PEG conjugates was founded on meaningful in vivo testing using established tumor models, and has led to a clinical candidate, PEG-camptothecin (PROTHECAN), an ester based prodrug currently in phase II trials. Additional applications of high molecular weight PEG prodrug strategies to amino containing drugs are presented: similar tripartate systems based on lower M(w) PEG and their use with proteins is expounded on. The modification of a benzyl elimination tripartate prodrug specific for mercaptans is presented, and its successful application to 6-mercaptopurine giving a water soluble formulation is discussed. Recent novel PEG oligonucleotides and immunoconjugates are also covered. Clinical results of FDA approved PEGylated proteins are also presented.     

The Influence of Face Shields on the Quality of Colonoscopy in the Era of the COVID-19 Pandemic

Background/AimsThe worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy.MethodsWe reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020.ResultsOf the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists.ConclusionsColonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.     

Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.