Development of Polyphosphate/Nanokaolin-Modified Alginate Sponge by Gas-Foaming and Plasma Glow Discharge Methods for Ultrarapid Hemostasis in Noncompressible Bleeding.

Effective bleeding management strategies in uncontrollable and noncompressible massive hemorrhage are becoming important in both clinical and combat situations. Here, a novel approach was developed to create a superporous and highly absorbable hemostatic sponge through a facile chemical gas-foaming method by cross-linking long-chain polyphosphate along with nanokaolin and Ca2+ in an alginate structure to synergistically activate the coagulation pathway. Natural kaolin obtained from the Marand mine in East Azarbaijan was converted into pseudohexagonal-shaped kaolin nanoparticles (30 to 150 nm) using ball milling followed by a newly developed glow discharge plasma treatment method. The obtained ultralight sponges (>90% porosity) exhibit ultrarapid water/blood absorption capacity (∼4000%) and excellent shape memory, which effectively concentrates coagulation factors. The results of in vitro tests demonstrated that the proposed sponges exhibited enhanced blood clotting ability (BCI < 10%) and superior cohesion with red blood cells (∼100) and platelets (∼80%) compared to commercially available hemostatic products. The in vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological, and biochemical parameter assessments. In a rat femoral artery complete excision model, the application of alginate/k/polyp nanocomposite sponges resulted in a complete hemostasis time of 60 s by significant reduction of hemostasis time (∼6.7-8.3 fold) and blood loss (∼2-2.8-fold) compared to commercially available hemostatic agents (P < 0.001). In conclusion, distinct physical characteristics accompanied by unique chemical composition multifunctional sponges activate hemostasis synergistically by triggering the XII, XI, X, IX, V, and II factors and the contact pathway and have the ability of rapid hemostasis in noncompressible severe bleeding.

Extracellular and intracellular antiviral effects of ultraviolet A against severe acute respiratory syndrome coronavirus-2 are variant-independent.

Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. RESULTS: SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. CONCLUSION: Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.

Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing.

BACKGROUND& AIMS: Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. METHODS: Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. RESULTS: A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N = 66) and ≥105 CFU/mL (N = 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P < .0001) and Klebsiella (P = .0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N = 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. CONCLUSIONS: Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide-related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities.

Use of Fantasy Points in Evaluating Professional Athlete Performance After Anterior Cruciate Ligament (ACL) Reconstruction.

Our aim in performing this study was to evaluate whether fantasy and wins above replacement (WAR) scores of athletes undergoing anterior cruciate ligament (ACL) reconstructive surgery in the National Football League (NFL), National Basketball Association (NBA), National Hockey League (NHL), and Major League Baseball (MLB) could be utilized in evaluating their performance post-surgery. We identified publicly accessible data on professional athletes from 1992 to 2015. Fantasy and WAR scores were calculated for each player. A total of 83 professional players met the inclusion criteria for this cross-sectional study. Decreased fantasy scores ranged from 33% to 42% across the four leagues after the index operation. NHL players had the lowest return-to-play (RTP) rate at 11/17 (82%), and MLB players had the highest RTP rate at 14/15 (93%). RTP rates of NBA and NFL players were comparable at 22/26 (85%) and 22/25 (88%), respectively. NFL players had the lowest average career length after surgery at 26 months, while NBA players had the longest average career length at 64 months. MLB players on average required the longest time to return to the pre-surgical level of performance (21 months). NHL players had the shortest average recovery time (eight months), and NBA players had the longest average recovery time (13 months). Approximately, more than half of all the studied players exhibited a decline in fantasy or WAR scores. In addition, NFL players had the lowest average career length, and NBA players enjoyed the longest average career length after surgery. NHL players had the lowest recovery time, while NBA players had the longest recovery time. The strength of this study is the utilization of fantasy points and WAR scores as a single unifying measure of a player's performance, which acts as an objective measure after ACL reconstruction. The average performance of a professional athlete, as evaluated through their fantasy score output, tends to decrease after undergoing ACL reconstruction. There is an overall long-term performance decline after initial spikes in their performance after surgery. Additional larger studies are needed to fully understand the effects of ACL reconstruction in professional athletes; however, the use of fantasy scores may be an objective tool in measuring the success rate of ACL reconstruction.

Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS: Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS: Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION: Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.

Rotationplasty with Tibial Nerve Coaptation: A Case Report.

CASE: We present the case of a 14-year-old adolescent boy with a distal femoral osteosarcoma partially encasing the tibial nerve. He underwent rotationplasty with resection and coaptation (end-to-end repair) of the tibial nerve. By 1 year postoperatively, he had recovered sensation on the plantar aspect of his foot and Medical Research Council scale 4+/5 gastro-soleus contraction that powered extension of the new knee. CONCLUSION: Tibial nerve resection is not an absolute contraindication for rotationplasty, even in an adolescent. Nerve coaptation allows for well-functioning rotationplasty as an alternative to endoprosthetic reconstruction or above-knee amputation.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.

Smoking has disruptive effects on the small bowel luminal microbiome.

Tobacco use is the leading preventable cause of cancer, and affects the respiratory, oral, fecal, and duodenal mucosa-associated microbiota. However, the effects of smoking on the duodenal luminal microbiome have not been studied directly. We aimed to compare the duodenal luminal microbiome in never-smokers, current smokers, and ex-smokers who quit ≥ 10 years ago. In a cross-sectional study, current smokers (CS, n = 24) were identified and matched to never-smokers (NS, n = 27) and ex-smokers (XS, n = 27) by age (± 5 years), body mass index (BMI, ± 3 kg/m2), and sex. Current antibiotic users were excluded. The duodenal luminal microbiome was analysed in 1 aspirate sample per subject by 16S rRNA gene sequencing. Relative abundances (RA) of families associated with increased duodenal microbial diversity, Prevotellaceae, Neisseriaceae, and Porphyromonadaceae, were significantly lower in CS vs. NS. This was driven by lower RA of unknown Prevotella and Porphyromonas species, and Neisseria subflava and N. cinerea, in CS. In contrast, RA of Enterobacteriaceae and Lactobacillaceae (associated with decreased diversity), were significantly higher in CS, due to higher RA of Escherichia-Shigella, Klebsiella and Lactobacillus species. Many of these changes were absent or less pronounced in XS, who exhibited a duodenal luminal microbiome more similar to NS. RA of taxa previously found to be increased in the oral and respiratory microbiota of smokers were also higher in the duodenal luminal microbiome, including Bulledia extructa and an unknown Filifactor species. In conclusion, smoking is associated with an altered duodenal luminal microbiome. However, ex-smokers have a duodenal luminal microbiome that is similar to never-smokers.

Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes.

BACKGROUND: Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut. AIMS: To compare the duodenal and stool microbiomes in PPI and non-PPI users. METHODS: Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing. RESULTS: The duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 103 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects. CONCLUSIONS: These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.

Question Prompt List as a Communication Tool for Adults With Gastroesophageal Reflux Disease: Incorporation of Patients' Perspectives.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients' perspectives and opinions on each question, however, had not been accounted for in the preliminary expert' version. AIM: The aim was to modify a preliminary experts' QPL, specific to adults with GERD, following patient perspectives and opinions. METHODS: A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1="should not be included," 2="unimportant," 3="don't know/depends," 4="important," and 5="essential." Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" RESULTS: Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of "what habits, food, and drinks do I have to avoid?" (82.6%). Questions eliminated because of disagreement included "What is the natural history of GERD," "Do I have a high chance to die from my Barrett's?," and "Why are you prescribing an antidepressant to treat my GERD?" Nine patients suggested additional questions totaling to 16 separate questions, including "What type of surgeries are there to help GERD?," "What stage is my GERD?," "What are the odds/percentage of getting cancer from GERD?" Incorporating the suggested questions, the final GERD QPL-created by esophageal experts and modified by patients-consisted of 82 questions. CONCLUSION: Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients' decisional conflict and perceived involvement in care.

Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells via cell-cell signaling.

Mitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E (CoV-229E), and results in increased intracellular levels of MAVS. In this study, we explored the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (e.g. via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 min and in unexposed controls at 30-40% and at 100% confluency, and in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. MAVS was also assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. Our results showed that UVA increases the expression of MAVS protein. Further, cells in a confluent monolayer exposed to UVA conferred an elevation in MAVS in cells adjacent to the exposed section, and also in cells in the most distant sections which were not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to confluent cells not exposed to UVA, likely via cell-cell signaling.

Primary Synovial Osteochondromatosis of the Shoulder in Pediatric Patient: Case Report and Review of the Literature.

We report a primary synovial osteochondromatosis in a 6-year-old male with a 1-year history of shoulder pain and stiffness. The patient underwent surgical treatment, resulting in significant improvement in range of motion and functional status. Primary synovial osteochondromatosis of the shoulder is a rare benign condition that can result in shoulder pain, stiffness, and locking. MRI helps identify these lesions within the affected joint. Removal of loose bodies often alleviates symptoms and allows for improved range of motion with satisfactory results.

Comparative Analysis of the Effectiveness of Intra-Articular Injection of Platelet-Rich Plasma versus Hyaluronic Acid for Knee Osteoarthritis: Results of an Open-Label Trial.

BACKGROUND: Platelet-rich plasma (PRP), an autologous source of growth factors, and hyaluronic acid (HA) are among the minimally invasive treatments for knee osteoarthritis (OA). This trial was designed to compare the effectiveness of intra-articular injection of PRP with HA (as one of the standard treatments) on mild to moderate knee OA. METHODS: In this phase I open-label clinical trial, 10 patients underwent intra-articular PRP injection and 10 others received HA injection. At baseline (pre-injection) visit and 1, 3, 6, and 12 months post-injection, clinical assessments were performed using visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Physical examinations of the knee, including crepitation and range of motion (ROM) were performed at each visit. The follow-up responses were compared with the baseline visit. RESULTS: The PRP treatment was ascertained to be safe and caused no adverse effects. Significant improvements in the majority of KOOS subscales and VAS were found throughout the entire 12-month follow-up, following the PRP injections. HA injection, however, caused only one month significant improvement in the majority of patient-reported outcomes. In the majority of visits, the extent of improvements in the scores of KOOS subscales, as well as the extent of reduction in VAS were significantly greater in PRP recipients, compared to HA recipients. The ROM in both groups slightly increased after interventions. The frequency of coarse crepitation, which was detected in 100% of the patients in both groups at the baseline visit, decreased significantly to fine crepitation at the first follow-up visit in 80% and 40% of the PRP and HA recipients, respectively. CONCLUSION: Intra-articular injection of PRP or HA alleviates symptoms and pain and improves functionality and physical examinations in patients with knee OA. However, PRP therapy produces greater and longer-lasting improvements in most of the outcome parameters compared to HA.

Intraoperative measurement of acetabular component position using imageless navigation during revision total hip arthroplasty.

BACKGROUND: Acetabular component malposition is a major cause of dislocation following total hip arthroplasty (THA). Intellijoint HIP is an imageless navigation tool that has been shown to provide accurate intraoperative measurement of cup position during primary THA without substantially increasing operative time. However, its accuracy in revision THA has not been evaluated. This study therefore aims to assess the accuracy of Intellijoint HIP in measuring cup inclination and anteversion in comparison with computed tomography (CT) during revision THA. METHODS: Intellijoint HIP was used to measure the position of the preexisting cup in 53 consecutive patients undergoing revision THA between December 2018 and February 2020. Two authors blinded to the intraoperative navigation measurements also independently measured cup position using preoperative CT according to Murray's radiographic definitions. Pearson correlation coefficients with 95% confidence intervals (CIs), paired t tests and Bland-Altman plots were used to assess agreement between navigation- and CT-measured cup position. Statistical analysis was performed using GraphPad Prism, with p values less than 0.05 indicating statistical significance. RESULTS: There was excellent agreement between navigation and CT measurements for both cup inclination (r = 0.89, 95% CI 0.81-0.93) and anteversion (r = 0.93, 95% CI 0.88-0.96), with the mean absolute difference being 5.2º (standard deviation [SD] 4.0º) for inclination and 4.8º (SD 5.4º) for anteversion. The navigation measurement was within 10º of the radiographic measurement in 47 of 53 (88.7%) cases for inclination and 46 of 53 (86.8%) cases for anteversion. CONCLUSION: Imageless navigation demonstrated excellent correlation and agreement with CT measurements for both inclination and anteversion over a wide range of acetabular component positions.

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus.

BACKGROUND: An important clinical feature of coronavirus disease 2019 (COVID-19) is hypercytokinemia (cytokine storm). We previously showed that narrow band ultraviolet-A (NB-UVA) treatment salvages coronavirus (CoV)-229E-infected human tracheal cells, and that daily endotracheal NB-UVA therapy reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in human subjects, with improved clinical outcomes. Here, we examined NB-UVA effects on cytokine release during CoV-229E infection. METHODS: Primary human tracheal epithelial cells were transfected with CoV-229E, then exposed to 2 mW/cm2 NB-UVA for 20 minutes every 24h, either 3 or 4 times. Secreted cytokine/chemokine levels were analyzed in supernatants collected from CoV-229E-infected/UVA-exposed cells 24h after the last UVA treatment, and from matched non-infected/UVA-exposed controls, CoV-229E-infected/non-exposed controls, and non-infected/non-exposed (naïve) controls. Metabolic pathway/downstream prediction analyses were also performed. RESULTS: Pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF), and chemokines IL-8, monocyte chemoattractant protein-1 (MCP1), and interferon gamma-induced protein 10 (IP-10), were significantly increased in CoV-229E-infected cells, and significantly decreased following NB-UVA treatment. Interferon (IFN)-α2, IFN-γ, and IL-10 were not upregulated in response to CoV-229E. Metabolic pathway predictions indicated hypercytokinemia as the top inflammatory response in CoV-229E-infected cells, whereas the top predicted pathway in CoV-229E-infected/UVA-exposed cells was the recovery stage of severe acute respiratory syndrome. CONCLUSIONS: Human tracheal epithelial cells infected with CoV-229E showed reduced cytokine secretions including IL-6, TNF, IL-8, and MCP-1, following NB-UVA exposure. This reduction of cytokine levels in vitro, coupled with previously identified reduced cell death in CoV-229E-infected/UVA-exposed cells, suggests that determining UVA effects on cytokine storm in human SARS-Co-V2 patients is warranted.

Mast Cell Activation Syndrome: A Primer for the Gastroenterologist.

Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers. Gastroenterologists manage diseases associated with active inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. The mast cell has only recently been recognized as a major player in our specialty. Gastrointestinal disorders from mast cell mediators often present with apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn. Individuals with mast cell activation syndrome experience significant delays in diagnosis. The gastrointestinal symptoms are often refractory to symptom-targeted prescription medications. Beyond avoiding triggers, the best therapy is directed at modulating mast cell activation and the effects of the mediators. Many of these therapies are simple over-the-counter medications. In this article, we review mast cell function and dysfunction and the gastrointestinal symptoms, comorbid conditions, diagnosis, and management of mast cell activation syndrome. Gastroenterologists who become aware of this syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.

The duodenal microbiome is altered in small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth (SIBO) is highly prevalent and is associated with numerous gastrointestinal disorders, but the microbes involved remain poorly defined. Moreover, existing studies of microbiome alterations in SIBO have utilized stool samples, which are not representative of the entire gastrointestinal tract. Therefore, we aimed to determine and compare the duodenal microbiome composition in SIBO and non-SIBO subjects, using duodenal aspirates from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Using the recently-redefined cutoff for SIBO of >103 colony forming units per milliliter (CFU/mL), 42 SIBO and 98 non-SIBO subjects were identified. Duodenal samples from SIBO subjects had 4x103-fold higher counts than non-SIBO subjects when plated on MacConkey agar (P<0.0001), and 3.8-fold higher counts when plated on blood agar (P<0.0001). Twenty subjects had also undergone lactulose hydrogen breath tests (LHBTs), of whom 7/20 had SIBO. At the 90-minute timepoint, 4/7 SIBO subjects had positive LHBTs (rise in hydrogen (H2) ≥ 20 ppm above baseline), as compared to 2/13 non-SIBO subjects. 16S ribosomal RNA (rRNA) sequencing revealed that SIBO subjects had 4.31-fold higher relative abundance of Proteobacteria (FDR P<0.0001) and 1.64-fold lower Firmicutes (P<0.0003) than non-SIBO subjects. This increased relative abundance of Proteobacteria correlated with decreased α-diversity in SIBO subjects (Spearman R = 0.4866, P<0.0001) Specific increases in class Gammaproteobacteria correlated with the area-under-the-curve for H2 for 0-90 mins during LHBT (R = 0.630, P = 0.002). Increases in Gammaproteobacteria resulted primarily from higher relative abundances of the family Enterobacteriaceae (FDR P<0.0001), which correlated with the symptom of bloating (Spearman R = 0.185, 2-tailed P = 0.028). Increases in family Aeromonadaceae correlated with urgency with bowel movement (Spearman R = 0.186, 2-tailed P = 0.028). These results validate the >103 CFU/mL cutoff for the definition of SIBO, and also reveal specific overgrowth of Proteobacteria in SIBO vs. non-SIBO subjects, coupled with an altered Proteobacterial profile that correlates with symptom severity. Future research may elucidate host-microbiome interactions underlying these symptoms in SIBO patients.

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus.

Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.