Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification.

Background: People living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). The serum immune factors associated with the onset of SSTI are not well understood. Methods: We conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electro-chemiluminescence based multiplex assay platform. Results: Of 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI. Conclusion: The study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): A multicenter US study on long-term follow-up and fistula closure.

Background and study aims Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a safe and efficacious procedure to treat pancreaticobiliary diseases in Roux-en-Y gastric bypass (RYGB). This multicenter study aimed to determine the long-term outcomes of EDGE focusing on fistula persistence rates and post-procedure weight change. Patients and methods Information about patients with Roux-en-Y gastric bypass anatomy who underwent EDGE between 2015 and 2021 from 10 institutions was captured in a registry. Patient demographics, procedural details, and clinical outcomes were analyzed. Results One hundred seventy-two patients were included in the study (mean age 60, 25 % male). Technical success of lumen-apposing metal stent (LAMS) placement was 171 of 172 (99.4 %) while clinical success of intervention was 95%. The mean procedure time was 65 minutes. The most commonly reported complication was stent dislodgement/migration (n = 29, 17). Mean length of time of LAMS duration was 69 days. Mean follow-up time was 6 months. Endoscopic fistula closure was performed in 40 % of patients (69/172) at the time of LAMS removal. Persistence of fistula was observed in 19 of 62 patients (31 %) assessed. Length of LAMS indwell time (days) was a predictor of persistent fistula. The average weight gain while the LAMS was in place was 12 lb in 63 patients (36.6 %); 59.4 % of patients gained < 5 lb. Conclusions EDGE is a safe and efficacious procedure for RYGB patients requiring ERCP. Post-procedure evaluation and management of the enteral fistula varies widely among centers currently and would benefit from further standardization. Fistula persistence appears to be uncommon and can be managed endoscopically but may be related to length of indwell times of the LAMS.

Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis.

BACKGROUND: Intravenous magnesium (IV Mg), a commonly utilized therapeutic agent in the management of atrial fibrillation (AF) with rapid ventricular response, is thought to exert its influence via its effect on cellular automaticity and prolongation of atrial and atrioventricular nodal refractoriness thus reducing ventricular rate. We sought to undertake a systematic review and meta-analysis of the effectiveness of IV Mg versus placebo in addition to standard pharmacotherapy in the rate and rhythm control of AF in the nonpostoperative patient cohort given that randomized control trials (RCTs) have shown conflicting results. METHODS: Randomized controlled trials comparing IV Mg versus placebo in addition to standard of care were identified via electronic database searches. Nine RCTs were returned with a total of 1048 patients. Primary efficacy endpoints were study-defined rate control and rhythm control/reversion to sinus rhythm. The secondary endpoint was patient experienced side effects. RESULTS: Our analysis found IV Mg in addition to standard care was successful in achieving rate control (odd ratio [OR] 1.87, 95% confidence interval [CI] 1.13-3.11, p = .02) and rhythm control (OR 1.45, 95% CI 1.04-2.03, p = .03). Although not well reported among studies, there was no significant difference between groups regarding the likelihood of experiencing side effects. CONCLUSIONS: IV Mg, in addition to standard-of-care pharmacotherapy, increases the rates of successful rate and rhythm control in nonpostoperative patients with AF with rapid ventricular response and is well tolerated.

Digital biosensor for human cerebrospinal fluid detection with single-use sensing strips.

Leakage of human cerebrospinal fluid (CSF) caused by trauma or other reasons presents exceptional challenges in clinical analysis and can have severe medical repercussions. Conventional test methods, including enzyme-linked immunosorbent assay and immunofixation electrophoresis testing, typically are performed at a few clinical reference laboratories, which may potentially delay proper diagnosis and treatment. At the same time, medical imaging can serve as a secondary diagnosis tool. This work presented here reports the use of a point-of-care electrochemical sensor for detection of beta-2-transferrin (B2T), a unique isomer of transferrin that is present exclusively in human CSF but is absent in other bodily fluids. Limits of detection were examined via serial dilution of human samples with known B2T concentrations down to 7 × 10-12 g B2T/ml while maintaining excellent sensitivity. Nine human samples with varying levels of B2T were compared using up to 100 times dilution to confirm the validity of sensor output across different patient samples.

Nasal microbiota evolution within the congregate setting imposed by military training.

The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach.

An Evaluation of Gaming-Related Harms in Relation to Gaming Disorder and Loot Box Involvement.

The specific nature of harm and functional impairment in the context of gaming disorder (GD) has received limited attention. In this study, we present one of the first concerted attempts to measure the types and degree of harm experienced by people displaying signs of problem gaming. Attempts were made to assess the extent to which types of harm were attributable to gaming as opposed to other factors. The study also investigated potential behavioural indicators of harmful involvement, including exposure to loot boxes. A sample of 471 regular gamers (M = 380, F = 73), recruited through the online platform Prolific, completed a survey where problem gaming was identified using Petry et al.'s (2014) checklist. Individuals who met the cut-off for gaming disorder scored higher than the non-problem group on most dimensions of harm, with physical and psychological types being the most common issues. Loot box expenditure was low (M = $25 in 3 months, for the 10.8% of respondents who played loot boxes) but significantly positively associated with the degree of gaming-related financial harm. This study shows that problem gaming is most strongly associated with physical or psychological harm and that financial harms may manifest in gaming activities that facilitate continuous spending options.

Fast SARS-CoV-2 virus detection using disposable cartridge strips and a semiconductor-based biosensor platform.

Detection of the SARS-CoV-2 spike protein and inactivated virus was achieved using disposable and biofunctionalized functional strips, which can be connected externally to a reusable printed circuit board for signal amplification with an embedded metal-oxide-semiconductor field-effect transistor (MOSFET). A series of chemical reactions was performed to immobilize both a monoclonal antibody and a polyclonal antibody onto the Au-plated electrode used as the sensing surface. An important step in the biofunctionalization, namely, the formation of Au-plated clusters on the sensor strips, was verified by scanning electron microscopy, as well as electrical measurements, to confirm successful binding of thiol groups on this Au surface. The functionalized sensor was externally connected to the gate electrode of the MOSFET, and synchronous pulses were applied to both the sensing strip and the drain contact of the MOSFET. The resulting changes in the dynamics of drain waveforms were converted into analog voltages and digital readouts, which correlate with the concentration of proteins and virus present in the tested solution. A broad range of protein concentrations from 1 fg/ml to 10 µg/ml and virus concentrations from 100 to 2500 PFU/ml were detectable for the sensor functionalized with both antibodies. The results show the potential of this approach for the development of a portable, low-cost, and disposable cartridge sensor system for point-of-care detection of viral diseases.

Safety, immunogenicity, and efficacy of NDV-3A against Staphylococcus aureus colonization: A phase 2 vaccine trial among US Army Infantry trainees.

BACKGROUND: Military trainees are at increased risk for Staphylococcus aureus colonization and infection. Disease prevention strategies are needed, but a S. aureus vaccine does not currently exist. METHODS: We enrolled US Army Infantry trainees (Fort Benning, GA) in a phase 2, randomized, double-blind, placebo-controlled trial of NDV-3A, a vaccine containing a recombinant adhesin/invasion protein of Candida albicans that has structural similarity to the S. aureus protein clumping factor A. Study participants received one intramuscular dose of NDV-3A or placebo (adjuvant alone) within 72 h of arrival on base. Longitudinal nasal and oral (throat) swabs were collected throughout the 14-week Infantry training cycle. Safety, immunogenicity, and efficacy of NDV-3A against S. aureus nasal / oral acquisition were the endpoints. RESULTS: The NDV-3A candidate had minimal reactogenicity and elicited robust antigen-specific B- and T-cell responses. During the 56-day post-vaccination period, there was no difference in the incidence of S. aureus nasal acquisition between those who were randomized to receive NDV-3A vs. placebo (25.6% vs. 29.1%; vaccine efficacy [VE]: 12.1%; p = 0.31). In time-to-event analysis, there was no difference between study groups with respect to the S. aureus colonization-free interval (VE: 13%; p = 0.29). Similarly, the efficacy of NDV-3A against S. aureus oral acquisition was poor (VE: 2.4%; p = 0.52). CONCLUSIONS: A single dose of NDV-3A did not prevent nasal nor oral acquisition of S. aureus in a population of military trainees at high risk for colonization.

Hydroxyapatite Formation on Coated Titanium Implants Submerged in Simulated Body Fluid.

Titanium implants are commonly used in the field of dentistry for prosthetics such as crowns, bridges, and dentures. For successful therapy, an implant must bind to the surrounding bone in a process known as osseointegration. The objective for this ongoing study is to determine the potential of different implant surface coatings in providing the formation of hydroxyapatite (HA). The coatings include titanium nitride (TiN), silicon dioxide (SiO2), and quaternized titanium nitride (QTiN). The controls were a sodium hydroxide treated group, which functioned as a positive control, and an uncoated titanium group. Each coated disc was submerged in simulated body fluid (SBF), replenished every 48 h, over a period of 28 days. Each coating successfully developed a layer of HA, which was calculated through mass comparisons and observed using scanning electron microscopy (SEM) and energy dispersive analysis x-rays (EDX). Among these coatings, the quaternized titanium nitride coating seemed to have a better yield of HA. Further studies to expand the data concerning this experiment are underway.

A Two-Electrode, Double-Pulsed Sensor Readout Circuit for Cardiac Troponin I Measurement.

This paper presents a pulse-stimulus sensor readout circuit for use in cardiovascular disease examinations. The sensor is based on a gold nanoparticle plate with an antibody post-modification. The proposed system utilizes gated pulses to detect the biomarker Cardiac Troponin I in an ionic solution. The characteristic of the electrostatic double-layer capacitor generated by the analyte is related to the concentration of Cardiac Troponin I in the solvent. After sensing by the transistor, a current-to-frequency converter (I-to-F) and delay-line-based time-to-digital converter (TDC) convert the information into a series of digital codes for further analysis. The design is fabricated in a 0.18-µm standard CMOS process. The chip occupies an area of 0.92 mm2 and consumes 125 µW. In the measurements, the proposed circuit achieved a 1.77 Hz/pg-mL sensitivity and 72.43 dB dynamic range.

Application of exome sequencing to diagnose a novel presentation of the Cornelia de Lange syndrome in an Afro-Caribbean family.

BACKGROUND: Cornelia de Lange syndrome (CdLS) comprises a recognizable pattern of multiple congenital anomalies caused by variants of the DNA cohesion complex. Affected individuals may display a wide range of phenotypic severity, even within the same family. METHODS: Exome sequencing and confirmatory Sanger sequencing showed the same previously described p.Arg629Ter NIPBL variant in two half-brothers affected with CdLS. Clinical evaluations were obtained in a pro bono genetics clinic. RESULTS: One brother had relatively mild proportionate limb shortening; the other had complete bilateral hypogenesis of the upper arm with absence of lower arm structures, terminal transverse defects, and no digit remnants. His complex lower limb presentation included long bone deficiency and a deviated left foot. The mother had intellectual disability and microcephaly but lacked facial features diagnostic of the CdLS. CONCLUSION: We describe a collaboration between a pediatrics team from a resource-limited nation and USA-based medical geneticists. Reports describing individuals of West Indian ancestry are rarely found in the medical literature. Here, we present a family of Afro-Caribbean ancestry with CdLS presenting with phenotypic variability, including unusual lower limb abnormalities. The observation of this novel family adds to our knowledge of the phenotypic and molecular aspects of CdLS.

Anti-Bacterial Properties and Biocompatibility of Novel SiC Coating for Dental Ceramic.

A 200 nm plasma-enhanced chemical vapor-deposited SiC was used as a coating on dental ceramics to improve anti-bacterial properties for the applications of dental prosthesis. A thin SiO2 (20 nm) in the same system was deposited first, prior to SiC deposition, to improve the adhesion between SiC to dental ceramic. Silane and methane were the precursors for SiC deposition, and the SiO2 deposition employed silane and nitrous oxide as the precursors. SiC antimicrobial activity was evaluated on the proliferation of biofilm, Streptococcus sanguinis, and Streptococcus mutans on SiC-coated and uncoated dental ceramics for 24 h. The ceramic coating with SiC exhibited a biofilm coverage of 16.9%, whereas uncoated samples demonstrated a significantly higher biofilm coverage of 91.8%, measured with fluorescence and scanning electron microscopic images. The cytotoxicity of the SiC coating was evaluated using human periodontal ligament fibroblasts (HPdLF) by CellTiter-BlueCell viability assay. After 24 h of HPdLF cultivation, no obvious cytotoxicity was observed on the SiC coating and control group; both sets of samples exhibited similar cell adhesion and proliferation. SiC coating on a ceramic demonstrated antimicrobial activity without inducing cytotoxic effects.

Antibacterial Properties of Charged TiN Surfaces for Dental Implant Application.

The formation and characterization of positively surface charged TiN surfaces were investigated for improving dental implant survival. Surface nitrogen atoms of a traditional TiN implant were converted to a positive charge by a quaternization reaction which greatly increased the antibacterial efficiency. Ti, TiN, and quaternized TiN samples were incubated with human patient subgingival bacteria for 4 hours at 37°C in an anaerobic environment with an approximate 40% reduction in counts on the quaternized surface over traditional Ti and TiN. The samples were challenged with Streptococcus Mutans and fluorescent imaging confirmed significant reduction in the quaternized TiN over the traditional Ti and TiN. Contact angle measurement and X-Ray Photoelectron Spectroscopy (XPS) were utilized to confirm the surface chemistry changes. The XPS results found the charged quaternized nitrogen peak at 399.75 eV that is unique to the quaternized sample.

Crystal structure of (E)-4,4'-(but-2-ene-1,4-di-yl)bis-(2-meth-oxy-phenol).

The title compound, C18H20O4, was synthesized via the ruthenium-catalyzed alkene methathesis dimerization of eugenol. The whole mol-ecule is generated by inversion symmetry; the center of inversion being located at the mid-point of the trans C=C bond. The phenol ring is inclined to the mean plane of the central C-C=C-C unit (r.m.s. deviation = 0.014 Å) by 68.83 (16)°. In the crystal, mol-ecules are linked via O-H⋯O hydrogen bonds, involving the hy-droxy and meth-oxy groups, forming undulating sheets parallel to (010).

Severity of cough in idiopathic pulmonary fibrosis is associated with MUC5 B genotype.

BACKGROUND: A polymorphism (rs35705950) in the promoter region of the mucin MUC5B is associated with both familial and sporadic forms of idiopathic pulmonary fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the expression of cough, a frequent disabling symptom seen in subjects with IPF. METHODS: We genotyped 136 subjects with IPF. All living subjects were provided with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed allele effects of the MUC5B polymorphism on the LCQ scores using SAS General Linear Models (GLM) in the patients with IPF. RESULTS: In the 68 of the total 136 IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent with prior published studies (31%). We found a significant independent effect of the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is independent of other common causes of cough, including gastroesophogeal reflux disease and upper airway cough syndrome. CONCLUSIONS: Cough severity, a common disabling phenotypic component of IPF, is significantly associated with the presence of the minor allele of a MUC5B promoter polymorphism. This study highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary fibrosis.

Prevalence and effect of varicoceles in an elderly population.

OBJECTIVES: The prevalence of a varicocele in the adolescent and young adult populations is approximately 15%. Because other varicose veins increase in prevalence with advanced age, we hypothesized that the incidence of varicoceles in the elderly population would be greater and might affect testicular size, consistency, and function. METHODS: As part of a prostate cancer screening program, we prospectively evaluated 354 men (mean age 60.7 years) by physical examination for the presence of a varicocele, testicular size, and consistency, and measured the serum testosterone level. RESULTS: A varicocele was present bilaterally in 19.8% (70 of 354), left sided only in 22.0% (78 of 354), and right sided only in 1.1% (4 of 354) of patients. Decreased testosterone levels correlated with older age (P = 0.001) and the presence of bilaterally soft testes (P = 0.02) but not the presence of a varicocele. Testes in men with bilateral varicoceles were significantly smaller (P = 0.001) and softer (P = 0.001) than in men without varicoceles. Higher grade varicoceles were more likely to be associated with soft testes (P = 0.001) than were lower grade varicoceles. CONCLUSIONS: The 42% prevalence of varicoceles in our elderly population was greater than that for historic control younger populations, suggesting either an increase with age or examiner sensitivity bias. Varicoceles in the elderly, especially when bilateral, significantly affect testicular consistency (softer) and testicular size (smaller), but do not directly decrease serum testosterone levels. The presence of bilaterally soft testes in elderly men indicates bilateral gonadal dysfunction and may be a physical examination finding associated with decreased serum testosterone.

Varicocele--the most common cause of male factor infertility?

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.