Identification of State-Specific Proteomic and Transcriptomic Signatures of Microglia-Derived Extracellular Vesicles.

Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impact EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and noncoding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and omics communities and provide novel insights into the role of microglia-derived EVs in neuroinflammation.

A novel murine model mimicking male genital Neisseria species infection using Neisseria musculi†.

With ~78 million cases yearly, the sexually transmitted bacterium Neisseria gonorrhoeae is an urgent threat to global public health due to continued emergence of antimicrobial resistance. In the male reproductive tract, untreated infections may cause permanent damage, poor sperm quality, and subsequently subfertility. Currently, few animal models exist for N. gonorrhoeae infection, which has strict human tropism, and available models have limited translatability to human disease. The absence of appropriate models inhibits the development of vital new diagnostics and treatments. However, the discovery of Neisseria musculi, a mouse oral cavity bacterium, offers much promise. This bacterium has already been used to develop an oral Neisseria infection model, but the feasibility of establishing urogenital gonococcal models is unexplored. We inoculated mice via the intrapenile route with N. musculi. We assessed bacterial burden throughout the male reproductive tract, the systemic and tissue-specific immune response 2-weeks postinfection, and the effect of infection on sperm health. Neisseria musculi was found in penis (2/5) and vas deferens (3/5) tissues. Infection altered immune cell counts: CD19+ (spleen, lymph node, penis), F4/80+ (spleen, lymph node, epididymus), and Gr1+ (penis) compared with noninfected mice. This culminated in sperm from infected mice having poor viability, motility, and morphology. We hypothesize that in the absence of testis infection, infection and inflammation in other reproductive is sufficient to damage sperm quality. Many results herein are consistent with outcomes of gonorrhoea infection, indicating the potential of this model as a tool for enhancing the understanding of Neisseria infections of the human male reproductive tract.

Fixation of the proximal flange of a lumen-apposing metal stent using a through-the-scope endoscopic suturing system to prevent stent migration in single-session EUS-directed transgastric ERCP: a pilot study.

BACKGROUND AND AIMS: With the global obesity pandemic, clinical scenarios requiring urgent ERCP in patients with gastric bypass surgery are on the rise, and single-session EUS-directed transgastric ERCP (SS-EDGE) can effectively address these technical challenges. The aim of this study was to evaluate and describe the safe and effective use of a through-the-scope endoscopic suturing system for anchoring the lumen-apposing metal stents (LAMSs) during SS-EDGE. METHODS: Six patients with Roux-en-Y gastric bypass (RYGB) underwent SS-EDGE at our center. A through-the-scope endoscopic suturing system was used for anchoring the LAMSs during SS-EDGE. RESULTS: Clinical and technical success was achieved in all 6 patients without any adverse events related to the procedure. No stent migration, pneumoperitoneum, or GI perforation was noted. At the 4-week follow-up, no stent migration was noted, and the through-the-scope suturing system remained anchored. LAMSs along with tacks were removed, and gastric fistulae were successfully closed endoscopically in all patients to prevent weight gain. CONCLUSIONS: Use of through-the-scope endoscopic suturing can be a safe, reliable, and potentially cost-effective novel technique for LAMS fixation to successfully perform SS-EDGE in RYGB patients.

Indirect comparison of various lumen apposing metal stents for EUS-guided biliary and gallbladder drainage: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies assessing endoscopic ultrasound guided biliary drainage (EUS-BD) or gallbladder drainage (EUS-GB) using lumen apposing metal stents (LAMS) have shown variable results based on the type of LAMS. We performed a meta-analysis of the available data. METHODS: Multiple online databases were searched for studies using LAMS (AXIOS or SPAXUS) for EUS-BD and EUS-GB. The outcomes of interest were technical success, clinical success and adverse events. Pooled proportions along with 95% confidence intervals (CI) were calculated. RESULTS: A total of 18 observational studies were included: 11 for AXIOS stent (433 patients with mean age 72 years and 54% males) and 7 for SPAXUS stent (242 patients with mean age 74 years and 50% males). The respective pooled outcomes for AXIOS stent (EUS-BD and EUS-GB) were: technical success (96.2% and 96.2%), clinical success (92.8% and 92.7%), total adverse events (10.1% and 23.6%), and bleeding (3.7% and 4.8%). The respective pooled outcomes for SPAXUS stent (EUS-BD and EUS-GB) were: technical success (93.8% and 95.9%), clinical success (90.1% and 94.2%), total adverse events (12.6% and 9.5%), and bleeding (3.1% and 1.8%). CONCLUSION: AXIOS and SPAXUS stents demonstrate similar pooled technical and clinical success rates. Adverse events occurred in 23.6% patients (AXIOS stent) and 9.5% patients (SPAXUS stent) during EUS-GB.

Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions.

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

Au-courant and novel technologies for efficient doubled haploid development in barley (Hordeum vulgare L.).

Bounteous modern and innovative biotechnological tools have resulted in progressive development in the barley breeding program. Doubled haploids developed (homozygous lines) in a single generation is significant. Since the first discovery of haploid plants in 1920 and, in particular, after discovering in vitro androgenesis in 1964 by Guha and Maheshwari, the doubled haploidy techniques have been progressively developed and constantly improved. It has shortened the cultivar development time and has been extensively used in: genetic studies, gene mapping, marker/trait association, and QTL studies. In barley, the haploid occurrence developed gradually from being a sporadic and random process (spontaneous) to haploid development by in vivo method of modified pollination or by in vitro culture of immature male or female gametophytes. Although significant improvement in DH induction protocols has been made, challenges still exist for improvement in areas such as: low efficiency, albinism, genotypic specificity etc. Here, the paper focuses on: haploidization via different in vitro, in vivo techniques, the recent advances technologies like centromere-mediated haploidization, hap induction gene, and Doubled haploid CRISPR. The au-courant work of different researchers in barley using these technologies is reviewed. Studies on different factors affecting haploid induction and work on genome doubling of barley haploids to produce DH lines via spontaneous and induced technologies has also been highlighted.

Probing size-dependent defects in zinc oxide using synchrotron techniques: impact on photocatalytic efficiency.

In the present study, synchrotron-based X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS) and X-ray excited optical luminescence (XEOL) have been used to investigate the induced defect states in metal oxide nanomaterials. Specifically, two synthesis approaches have been followed to develop unique nano-sized peanut-shaped (N-ZnO) nanostructures and micron-sized hexagonal rods (M-ZnO). XANES analysis at the Zn K-edge revealed the presence of defect states with a divalent oxidation state of zinc (Zn2+) in a tetrahedral structure. Furthermore, XAS measurements performed at the Zn L3,2-edge and O K-edge confirm higher oxygen-related defects in M-ZnO, while N-ZnO appeared to have a higher concentration of surface defects due to size confinement. Moreover, the in-line XEOL and time dependent-XEOL measurements exposed the radiative excitonic recombination phenomena occurring in the band-tailing region as a function of absorption length, X-ray energy excitation, and time. Based on the chronology developed in the defect state improvement, a possible energy band diagram is proposed to accurately locate the defect states in the two systems. Furthermore, the increased absorption intensity at the Zn L3,2-edge and the O K-edge under the UV lamp suggests delayed recombination of electrons and holes, highlighting their potential use as photo catalysts. The photocatalytic activity degrading the rhodamine B dye established M-ZnO as a superior catalyst with a rapid degradation rate and significant mineralization. Overall, this work provides valuable insights into ZnO defect states and provides a foundation for efficient advanced materials for environmental or other optoelectronic applications.

A review on the recent applications of synthetic biopolymers in 3D printing for biomedical applications.

3D printing technology is an emerging method that gained extensive attention from researchers worldwide, especially in the health and medical fields. Biopolymers are an emerging class of materials offering excellent properties and flexibility for additive manufacturing. Biopolymers are widely used in biomedical applications in biosensing, immunotherapy, drug delivery, tissue engineering and regeneration, implants, and medical devices. Various biodegradable and non-biodegradable polymeric materials are considered as bio-ink for 3d printing. Here, we offer an extensive literature review on the current applications of synthetic biopolymers in the field of 3D printing. A trend in the publication of biopolymers in the last 10 years are focused on the review by analyzing more than 100 publications. Their application and classification based on biodegradability are discussed. The various studies, along with their practical applications, are elaborated in the subsequent sections for polyethylene, polypropylene, polycaprolactone, polylactide, etc. for biomedical applications. The disadvantages of various biopolymers are discussed, and future perspectives like combating biocompatibility problems using 3D printed biomaterials to build compatible prosthetics are also discussed and the potential application of using resin with the combination of biopolymers to build customized implants, personalized drug delivery systems and organ on a chip technologies are expected to open a new set of chances for the development of healthcare and regenerative medicine in the future.

Reducing the stigma surrounding opioid use disorder: evaluating an opioid overdose prevention training program applied to a diverse population.

BACKGROUND: The opioid epidemic is a rapidly growing public health concern in the USA, as the number of overdose deaths continues to increase each year. One strategy for combating the rising number of overdoses is through opioid overdose prevention programs (OOPPs). OBJECTIVE: To evaluate the effectiveness of an innovative OOPP, with changes in knowledge and attitudes serving as the primary outcome measures. METHODS: The OOPP was developed by a group of medical students under guidance from faculty advisors. Training sessions focused on understanding stigmatizing factors of opioid use disorder (OUD), as well as protocols for opioid overdose reversal through naloxone administration. Pre- and post-surveys were partially adapted from the opioid overdose attitudes and knowledge scales and administered to all participants. Paired t-tests were conducted to assess differences between pre- and post-surveys. RESULTS: A total of 440 individuals participated in the training; 381 completed all or the majority of the survey. Participants came from a diverse set of backgrounds, ages, and experiences. All three knowledge questions showed significant improvements. For attitude questions, significant improvements were found in all three questions evaluating confidence, two of three questions assessing attitudes towards overdose reversal, and four of five questions evaluating stigma and attitudes towards individuals with OUD. CONCLUSIONS: Our innovative OOPP was effective not only in increasing knowledge but also in improving attitudes towards overdose reversal and reducing stigma towards individuals with OUD. Given the strong improvements in attitudes towards those with OUD, efforts should be made to incorporate the unique focus on biopsychosocial and sociohistorical components into future OOPPs.

Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin. AIMS: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users. METHODS: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use). RESULTS: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort. CONCLUSIONS: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.

A Comparative Analysis of Online Versus in-Person Opioid Overdose Awareness and Reversal Training for First-Year Medical Students.

INTRODUCTION: Physicians trained in opioid use disorder (OUD) harm reduction can mitigate opioid overdose deaths by prescribing naloxone and educating patients about its use. Unfortunately, many physicians possess OUD stigma. Training during medical school presents an opportunity to reduce OUD stigma and improve opioid overdose reversal knowledge. This study assessed the efficacy of Opioid Overdose Awareness and Reversal Training (OOART) and evaluated the equivalency of the online and in-person OOART. Methods: Voluntary training was delivered to first-year medical (M1) students at one medical school. In 2018 and 2019, 29 and 68 M1 students, respectively, received in-person OOART training and completed pre- and post-training surveys. In 2020, 62 students participated in online OOART training, of which 53 completed both pre- and post-training surveys. Results: All three opioid overdose Knowledge questions showed significant improvements between pre- and post-training survey responses. For Attitude questions, six of eleven questions in 2019 and 2020 and four of eleven questions in 2018 had statistically significant improvements between pre- and post-training survey responses. There were no statistical differences between in-person and online post-training survey results for two out of the three Knowledge questions and all 11 Attitude questions. Conclusions: This study demonstrates that our OOART was effective in increasing opioid overdose reversal knowledge and reducing OUD stigma. There was no meaningful difference in outcomes between the training modalities. These results support the future expansion of online and in-person OOART to a larger population of medical students.

Limpid hydrogels from ß-turn motif-connected tandem repeats of Aß16-22.

Self-assembling peptides constitute an important class of functional biomaterials. A number of short amyloidogenic stretches have been identified from amyloid proteins. Such peptides, as such or through subtle modifications, can turn out to be promising candidates for functional biomaterials. End-capped Aß16-22, the well-studied amyloidogenic stretch from ß-amyloid, is reported to be non-hydrogelating up to 20 mM concentration. Here we investigated the hydrogelation propensity of Aß16-22 repeats connected through ß-turn-supporting motifs. The peptide repeats connected through Asn-Gly, Aib-DPro, and DPro-Gly formed transparent hydrogels at concentrations ≥2 mM. The repeats of the aromatic analog Aß16-22(F20Y) also resulted in similar hydrogels. Like other peptide-based gels reported earlier, these gels could trap the anticancer drug doxorubicin and displayed steady release in water. In addition, the gels supported the growth of mammalian cell lines, HEK-293 and RIN-5F. These data show that turn-inducing motifs can have marked effects on the hydrogelating propensity of self-assembling peptides.

Evaluation of surface glycoproteins of classical swine fever virus as immunogens and reagents for serological diagnosis of infections in pigs: a recombinant Newcastle disease virus approach.

Classical swine fever (CSF) is an important viral disease of domestic pigs and wild boar. The structural proteins E2 and Erns of classical swine fever virus (CSFV), which participate in the attachment of the virion to the host cell surface and its subsequent entry, are immunogenic. The E2 and Erns proteins are used for diagnosis and the development of vaccines against CSFV infection in swine. Newcastle disease virus (NDV) has been successfully used as a viral vector to express heterologous proteins. In the present study, the E2 and Erns proteins of CSFV were expressed in cell culture as well as embryonated chicken eggs, using recombinant NDV (rNDV). Rescued rNDV expressing the E2 and Erns proteins induced the production of CSFV-neutralizing antibodies upon intranasal vaccination of pigs. Serum samples from vaccinated animals were found to neutralize both homologous and heterologous CSFV strains. Furthermore, rNDV expressing the E2 and Erns proteins of CSFV was used to develop an indirect ELISA, which was used to measure the the antibody titers of randomly collected serum samples. The results suggested that the ELISA based on rNDV-expressed E2 and Erns proteins could be used to screen for CSFV infections. This study shows that rNDV-based expression of CSFV antigens is potentially applicable for development of vaccines and diagnostic tests for CSFV infection. This approach could be an economically favorable alternative to the existing vaccine and diagnostics for CSFV in pigs.

pH-Regulated anion transport activities of bis(iminourea) derivatives across the cell and vesicle membrane.

Recently, synthetic anion transporters have gained considerable attention because of their ability to disrupt cellular anion homeostasis and promote cell death. Herein, we report the development of bis(iminourea) derivatives as a new class of selective Cl- ion carrier. The bis(iminourea) derivatives were synthesized via a one-pot approach under mild reaction conditions. The presence of iminourea moieties suggests that the bis(iminourea) derivatives can be considered as unique guanidine mimics, indicating that the protonated framework could have much stronger anion recognition properties. The cooperative interactions of H+ and Cl- ions with these iminourea moieties results in the efficient transport of HCl across the lipid bilayer in an acidic environment. Under physiological conditions these compounds weakly transport Cl- ions via an antiport exchange mechanism. This pH-dependent gating/switching behavior (9-fold) within a narrow window could be due to the apparent pKa values (6.2-6.7) of the compounds within the lipid bilayer. The disruption of ionic homeostasis by the potent compounds was found to induce cell death.

Glycoprotein D peptide-based diagnostic approach for the detection of avian infectious laryngotracheitis antibodies.

Infectious laryngotracheitis (ILT) is a highly contagious respiratory disease of chickens, pheasants, and peafowl. It is caused by the alpha herpesvirus, infectious laryngotracheitis virus (ILTV). Glycoprotein D (gD) of ILTV is immunogenic and helps in its binding to the susceptible host cell receptor. In the present study, a recombinant gD protein was expressed in a prokaryotic system to develop a single serum dilution ELISA. In addition, two immunogenic peptides, corresponding to regions 77-89 and 317-328, were identified in gD protein. The peptides were synthesized using solid-phase peptide synthesis, purified using reversed-phase HPLC, and characterized using mass spectrometry. The peptides displayed a good titre and were found to be promising antigens to coat the ELISA plate to detect the ILTV antibodies in the serum sample. The developed ELISA showed 96.9% sensitivity, 87.5% specificity, and 95.3% accuracy as compared to OIE referenced standard indirect ILTV ELISA (whole viral coated). The assay may not differentiate vaccinated from infected birds when the flocks are administered with live attenuated vaccines. However, the assay could be useful to detect the disease condition in birds vaccinated with recombinant vaccine expressing glycoproteins other than gD. The developed ILTV single serum dilution ELISA could be an alternative to the existing diagnostics for the detection of ILTV antibodies.

Experimental Validation of Antidiabetic and Antioxidant Potential of Cassia tora (L.): An Indigenous Medicinal Plant.

The present study was undertaken to evaluate antidiabetic and antioxidant activities of Cassia tora (C. tora) seeds extract against streptozotocin induced diabetes in experimental rats to scientifically validate its use against diabetes. Ethanolic extract of C. tora seeds extract and standard drug (glibenclamide) prepared in aqueous gum acacia (2 %, w/v) suspension and fed orally to streptozotocin induced male adult diabetic rats of Charles Foster strain for 15 days. Biochemical parameters in normal, diabetic control, standard (600 µg/kg bw p.o.) and treated (500 mg/kg bw p.o.) animal groups were quantified and compared. Treatment of streptozotocin induced diabetic rats with ethanolic seeds extract caused significant (p < 0.001) reduction in blood glucose (270-220 mg/dl), total cholesterol (140-104 mg/dl), triglyceride (149-99 mg/dl), phospholipids (100-74 mg/dl), free fatty acid (2.39-2.00 µmol/l), lipid peroxide (9-5.63 nmol MDA/dl) and significantly increased post heparin lipolytic activity (11-14 nmol FFA released/h/l plasma) (p < 0.001). Furthermore, the seeds extract (100-400 µg) when tested for its antioxidant activity in vitro, showed significant (p < 0.001) inhibition in the generation of super oxide anions in enzymic system a (46-37, 33, 23, 21 nmol uric acid formed/min), in enzymic system b (113-91, 77, 60, 51 nmol formazon formed/min), non-enzymic system (324-230, 211, 161, 141 nmol uric acid formed/min) and hydroxyl radicals in enzymic system (544-501, 411, 319, 291 nmol 2,3-dihydroxybenzoate formed/h) and non-enzymic system (28-21, 17, 14, 12). The results of the present study demonstrated antidiabetic, antidyslipidemic and antioxidant activities of C. tora seeds which could help in prevention of diabeticdyslipidemia and related complications.

Impact of glucagon-like peptide receptor agonists on endoscopy and its preoperative management: Guidelines, challenges, and future directions.

Glucagon-like peptide receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus and, more recently, have garnered attention for their effectiveness in promoting weight loss. They have been associated with several gastrointestinal adverse effects, including nausea and vomiting. These side effects are presumed to be due to increased residual gastric contents. Given the potential risk of aspiration and based on limited data, the American Society of Anesthesiologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023. They included the duration of mandated cessation of GLP-1RA before sedation and usage of "full stomach" precautions if these medications were not appropriately held before the procedure. This has led to additional challenges, such as extended waiting time, higher costs, and increased risk for patients. In this editorial, we review the current societal guidelines, clinical practice, and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.

Adverse events associated with the gold probe and the injection gold probe devices used for endoscopic hemostasis: A MAUDE database analysis.

BACKGROUND: Gastrointestinal (GI) bleeding accounts for over half a million admissions annually and is the most common GI diagnosis requiring hospitalization in the United States. Bipolar electrocoagulation devices are used for the management of gastrointestinal bleeding. There is no data on device-related adverse events for gold probe (GP) and injection gold probe (IGP). AIM: To analyze this using the Food and Drug Administration (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database from 2013 to 2023. METHODS: We examined post-marketing surveillance data on GP and IGP from the FDA MAUDE database to report devicerelated and patient-related adverse events between 2013-2023. The MAUDE database is a publicly available resource providing over 4 million records relating to medical device safety. Statistical analyses were performed using IBM SPSS Statistics V.27.0 (IBM Corp., Armonk, NY, United States). RESULTS: Our search elicited 140 reports for GP and 202 reports for IGP, respectively, during the study period from January 2013 to August 2023. Malfunctions reportedly occurred in 130 cases for GP, and actual patient injury or event occurred in 10 patients. A total of 149 patients (74%) reported with Injection GP events suffered no significant consequences due to the device failure, but 53 patients (26%) were affected by an event. CONCLUSION: GP and IGP are critical in managing gastrointestinal bleeding. This study of the FDA MAUDE database revealed the type, number, and trends of reported device-related adverse events. The endoscopist and support staff must be aware of these device-related events and be equipped to manage them if they occur.

Role of macrophage colony stimulating factor and interferon regulatory factor 7 in modulating the immune profile of mouse testicular macrophages.

Testicular macrophages (TM) are critical for the function of the testis by regulating homeostasis and inflammatory responses. However, the mechanisms by which TM fulfil these roles remain elusive. In this study, we explored the impact of two key testicular microenvironmental factors, namely 25-hydroxycholesterol (25HC), an oxysterol related to sex hormones and macrophage colony-stimulating factor (M-CSF), a factor crucial for macrophage survival and differentiation, on the regulation of the TM phenotype. Specifically, we examined their role in controlling the expression of the transcription factor interferon regulatory factor 7 (Irf7), a factor critical for maintaining the alternative macrophage phenotype. To achieve this, we used an in vitro bone marrow-derived macrophage (BMDM) model as a surrogate for TM to investigate the roles of 25HC and M-CSF in regulating the expression of Irf7 during the polarization of murine TM. M-CSF was identified as the main regulator of Irf7 expression, while 25HC production is a consequence of Irf7 activation in BMDM. In turn, 25HC plays a role in a negative feedback loop on the expression levels of Irf7 in BMDM. Using flow cytometry in Irf7-/- mouse testis the CD64loMHChi TM subpopulation was found to be decreased. Together with lower IL-10 protein levels in Irf7-/- TM this indicates a shift towards an M1-like macrophage profile. In summary, our data indicates that M-CSF could act as an inducer of high Irf7 expression levels in the mouse testis. However, the exact role of the high 25HC concentration in the testis in maintaining the local immune milieu still needs further study.

Investigating the Characteristics of Nano-Graphite Composites Additively Manufactured Using Stereolithography.

Stereolithography has emerged as a recent method in fabricating complex structures with high accuracy. Components using resin have poorer properties. The current study investigates the improvement in the properties of nano-graphite composites fabricated by the SLA technique. The properties are compared for plain resin and 0.2%, 0.5%, 1%, 3%, and 5% (w/v) of nano-graphite mixed with the UV-curable resin. Various analyses were conducted, including viscosity, UV spectroscopy, moisture content, water absorption, gel content, tensile, bending, hardness testing, and microscopic characterization. The results from the experiments showed a difference in the results of each percentage of the specimen tested, such as the specimen property, which shows that the greater the percentage of nano-graphite added (5%), the opaquer the specimen will appear and less light will be reflected. Viscosity testing shows that the greater the percentage of nano-graphite added to the resin, the greater the viscosity. UV spectroscopy testing produced information about the electronic structure and the structure of molecules, such as their composition, purity, and concentration. Observations from the moisture content analysis found that the moisture content in specimens with higher percentages of nano-graphite affected physical and mechanical properties, leading to easier warping, cracking, decreased strength, etc. Tensile and bending testing shows that the greater the percentage of nano-graphite added, the greater the effect on physical and mechanical properties, including fracture. However, certain tests did not consistently yield significant variations among specimens when different percentages of nano-graphite were added, as particularly evident in chemical resistance testing. This study offers valuable insights into the application of nano-graphite composites fabricated via the SLA method.