Underwater Endoscopic Mucosal Resection Vs Conventional Endoscopic Mucosal Resection for Superficial Nonampullary Duodenal Epithelial Tumors in the Western Setting.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSIONS: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Preparation Regimens to Improve Capsule Endoscopy Visualization and Diagnostic Yield (PrepRICE): a multicenter randomized trial.

BACKGROUND AND AIMS: Current guidelines recommend bowel preparation before small-bowel capsule endoscopy (SBCE). However, the optimal protocol is yet to be defined. To determine the best timing for preparation in SBCE, we compared small-bowel visualization quality (SBVQ), diagnostic yield (DY), and patient-reported outcomes across 4 purgative regimens. METHODS: In this prospective, randomized (1:1:1:1), multicenter study, patients with suspected small-bowel bleeding were randomized into 4 arms: G1 (1 L of polyethylene glycol + ascorbic acid [Moviprep, Norgine, Amsterdam, Netherlands] the night before SBCE), G2 (1 L in the morning up to 2 hours before SBCE), G3 (0.5 L up to 2 hours before SBCE + 0.5 L after the capsule reached the duodenum), and G4 (1 L after the capsule reached the duodenum). To assess DY, lesions were categorized as having high (P2) or low (P0 or P1) bleeding potential. SBVQ was assessed using the Brotz score. Transit times were measured, and patient tolerability was scored from 0 to 5, with higher scores indicating better tolerability. RESULTS: A total of 387 patients were included, 59% female and with a median age of 73 years (interquartile range, 23). The examination completion rate was lower in G1 (90%, P < .001). Small-bowel transit time was shorter for patients receiving purgative during SBCE (G3 and G4, P = .001). SBVQ was better in patients receiving purgative after reaching the small bowel (P < .001): a median of 7 for G1, 8 for G2, and 9 for G3 and G4. The overall DY of patients receiving intraprocedure purgatives (G3 + G4) was superior (42.7 vs 31.3%, P = .02); significant differences were found in the second and third terciles. Likewise, G3 and G4 had higher angioectasia detection (P = .04). Patients' satisfaction was significantly superior for G4 (median, 4 points; interquartile range, 1). CONCLUSIONS: The group that received the bowel preparation the night before SBCE had poorer outcomes. Intraprocedure purgative regimens reduced SBTT, enhanced visualization, improved DY, and increased angioectasia detection. G4 was the best-tolerated regimen.

Lung abscess in a non-compliant patient with Crohn's disease.

A 66-year-old man was admitted to the emergency department due to malaise, fatigue and anorexia for the last 2 weeks. He presented no fever, no respiratory or gastrointestinal symptoms. The patient had been previously diagnosed with Crohn's Disease (CD) (A2L1L4B1 of Montreal Classification) 10 years before, when he presented complaints of watery diarrhea and unexplained weight loss. Despite refusing to start treatment, in the last staging exams performed 5 years before the admission (colonoscopy and magnetic resonance imaging) the patient was in deep remission. Nevertheless, he frequently missed his medical appointments and his disease had not been monitored since then. He denied previous use of corticosteroids, past abdominal surgery or previous CD related hospital admissions. He also denied smoking habits or chronic lung disease.

Effective submucosal tunneling endoscopic resection (STER) of a giant esophageal leiomyoma.

We report the successful removal of a giant esophageal leiomyoma using submucosal tunneling endoscopic resection in a 37-year-old woman with significant dysphagia.

Forecast models to predict the demand for endoscopic procedures in a tertiary unit: a prospective validation.

Over the past few decades, there has been an exponential increase in the utilization of endoscopic procedures. Accurately predicting the demand is crucial for effective capacity planning and resource allocation in the endoscopic unit. However, predictive models are not integrated into current endoscopy software. To overcome this limitation, our group used data on the demand in our tertiary unit from 2015 to 2021 (83 months) to develop forecast models using exponential smoothing techniques adjusted for trend and seasonality (derivation phase). These models were recently published at the Revista Española de Enfermedades Digestivas.

Are sarcopenia, frailty and malnutrition prognostic markers of liver disease decompensation in the ambulatory setting? - A prospective cohort study.

BACKGROUND: Sarcopenia, frailty and malnutrition are associated with adverse outcomes in liver cirrhosis. Studies assessing the prognostic value of these conditions in ambulatory patients with cirrhosis are scarce. METHODS: A prospective cohort study was conducted, with consecutive inclusion of all patients with cirrhosis observed in the Hepatology outpatient clinic of a Portuguese tertiary centre. At study enrolment, evaluation of muscle mass (ultrasound quadriceps femoris thickness), muscle strength (handgrip dynamometry) and nutritional status (Patient-Generated Subjective Global Assessment Short Form) was held. Follow-up ended upon the occurrence of a composite endpoint, comprising liver decompensation events and liver-related death, or last medical appointment/non-liver related death before the end of the study. The prognostic value of anthropometrical parameters and nutritional status in the composite endpoint was assessed using a multivariate Cox regression analysis, adjusted for several confounders. RESULTS: Ninety patients were enrolled (80% male), with a mean age of 63.5±10.5 years. The median follow-up was 30 (interquartile range 38) weeks, during which 12 patients reached the composite endpoint. These patients presented a lower mean handgrip strength [23.1±6.41 vs 30.3±10.4 Kg, p=0.04], compared to patients who did not reach the composite endpoint. On Cox regression multivariate analysis, however, no independent predictors of the composite endpoint were found, apart from previous decompensation episodes. CONCLUSION: In this study, muscle strength was lower in the group of patients with cirrhosis who presented a liver-related event. Handgrip strength might be a promising tool in the ambulatory setting to identify patients at risk of liver decompensation and liver-related death in the short term.

Maternal vaccination against group B Streptococcus glyceraldehyde-3-phosphate dehydrogenase leads to gut dysbiosis in the offspring.

Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1ß, IL-17A, RegIIIγ and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C+ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.

Deformation of implant retaining screws-Study with stereoscopic microscopy and microCT.

BACKGROUND: The prosthetic screw fixes the prostheses to the implants. Upon osteointegration, the untightening of the prosthetic screw is the most common problem in oral rehabilitation with implants. OBJECTIVE: To study the deformation of the implant retaining hexagonal screw head. METHODS: This investigation used two methods for evaluating the screw head's area of deformation (mm2 ): a stereoscopic microscopy and micro computed tomography (microCT). For stereoscopic microscopy, 16 titanium alloy (T) and 16 titanium gold-plated alloy (G) screws of the Zimmer Biomet™ brand were used, divided into eight groups: group 0 (control group), groups T1 and G1 (screws tightened 10 times to 20 Ncm), the groups T2 and G2 (screws tightened 20 times to 20 Ncm) and the groups T3 and G3 (screws tightened 10 times to 30 Ncm). In the study with microCT, one screw was randomly chosen from each of the groups described above to perform the scanning by microCT. RESULTS: When comparing the type of screw material using stereoscopic microscopy, no statistically significant differences were found (p > 0.05). Contrarily, different number of successive grips and different torque value showed statistically significant differences in the head section of the retaining screws (p < 0.05). The observation by microCT showed the torque applied is crucial to the head deformation in titanium screws. In gold-plated screws the successive tightening appears to be pivotal. CONCLUSION: Titanium and gold screws tend to behave similarly. By increasing the tightening cycles and the torque values of protocols greater levels of deformations can be expected. In general, microCT data showed better results for gold-plated titanium alloy. CLINICAL SIGNIFICANCE: To control severe screw head deformation and the impossibility of untightening the implant's restoration, clinicians should avoid extreme torque values and prevent surpassing 10 tightening cycles.

Digestive tract MALT lymphoma, an unusual location.

The authors describe a case of a rectal mucosa-associated lymphoid tissue lymphoma in a 78-year-old female patient, manifested as rectal bleeding. Despite being commonly diagnosed in the localized form, this patient had supradiaphragmatic involvement on disease staging. Immunochemotherapy was proposed due to the disseminated involvement and poorer prognosis.

Dynamic microfluidic bioreactor-Hip simulator (DMBH) system for implant toxicity monitoring.

The generation of degradation products (DPs) like ions and organo-metallic particles from corroding metallic implants is an important healthcare concern. These DPs generate local and systemic toxicity. The impact on local toxicity is well documented, however, little is known about systemic toxicity. This is mainly due to the limited scope of the current microtiter plate-based (static) toxicity assay techniques. These methods do not mimic the systemic (dynamic) conditions. In this study, it is hypothesized that DPs incubated with cells in static conditions might provide improper systemic toxicity results, as there is no movement mimicking the blood circulation around cells. This study reports the development of a three-chambered prototype microfluidic system connected to the operational hip implant simulator to test the cellular response induced by the DPs. This setup is called a dynamic microfluidic bioreactor-hip simulator system. We hypothesize that a dynamic microfluidic system will provide a realistic toxicology response induced by DPs than a static cell culture plate. To prove the hypothesis, Neuro2a (N2a) cells were used as representative cells to study systemic neurotoxicity by the implant DPs. The microfluidic bioreactor system was validated by comparing the cell toxicity against the traditional static system and using COMSOL modeling for media flow with DPs. The hip implant simulator used in this study was a state-of-the-art sliding hip simulator developed in our lab. The results suggested that static toxicity was significantly more compared to dynamic microfluidic-based toxicity. The newly developed DMBH system tested for in situ systemic toxicity on N2a cells and demonstrated very minimum toxicity level (5.23%) compared to static systems (31.16%). Thus, the new DMBH system is an efficient tool for in situ implant metal systemic toxicity testing.

GnRHa implants and size pairing effects on plasma and cephalic secretion sex steroids in Arapaima gigas.

Arapaima gigas, one of the world's largest freshwater fish, is considered an emerging species for aquaculture development in Brazil given its high growth rate and meat quality. However, the lack of reproductive control in captivity has limited the expansion of Arapaima farming. This study aimed to test the effects of hormonal induction using mGnRHa implants and size pairing on broodstock reproduction through the analyses of sex steroids. To do so, broodstock of different sizes (large, small or mixed) were paired and implanted. Plasma and cephalic secretion profiles of testosterone (T), 11-ketotestosterone (11-KT) and 17ß-oestradiol (E2) were analysed. Compared to control (non-implanted), implanted broodstock showed a significant increase in plasma 11-KT (large and small males) and T (large and mixed females) post GnRHa implantation. In females, a significant increase in plasma T levels was shown, however, E2 remained unchanged after implantation. Despite the lack of clear spawning induction, this study showed the potency of GnRHa on sex steroid production regardless of pairing groups. Interestingly, significant correlations between blood plasma and cephalic secretion levels of 11-KT in males and T in females were observed, indicating the possible release of pheromones through the cephalic canals of A. gigas.

Role of Interleukin 32 in Human Immunodeficiency Virus Reactivation and Its Link to Human Immunodeficiency Virus-Herpes Simplex Virus Coinfection.

Background: Herpes simplex virus type 2 (HSV-2; herpes) exacerbates human immunodeficiency virus type 1 (HIV) by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T-cells and HIV reservoirs. Methods: Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative and HIV-uninfected controls were analyzed by flow cytometry. Cell-associated HIV DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant interleukin 32γ (IL-32γ), and a RUNX1 inhibitor. RNA was assessed by nanostring. Results: CD4, but not CD8, T-cell phenotypes differed in HIV+/HSV-2+ versus HIV+/HSV-2- (overall P = .002) with increased frequency of CCR5+, CXCR4+, PD-1+, and CD69+ and decreased frequency of CCR10+ and CCR6+ T-cells. The changes were associated with higher HIV DNA. Paradoxically, IL-32, a proinflammatory cytokine, was lower in subpopulations of CD4+ T-cells in HSV-2+ versus HSV-2- women. Recombinant IL-32γ blocked HIV reactivation in CD4+ T-cells and was associated with an increase in RUNX1 expression; the blockade was overcome by a RUNX1 inhibitor. Conclusions: Herpes is associated with phenotypic changes in CD4+ T-cells, including a decrease in IL-32, which may contribute to increased HIV reservoirs. Blocking IL-32 may facilitate HIV reactivation to improve shock and kill strategies.

Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges.

Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 10(5) ng/mL (range 1.1 × 10(4) to 6.6 × 10(5) ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans.

Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques.

We evaluated the in vivo pharmacokinetics and used a complementary ex vivo coculture assay to determine the pharmacodynamics of IQB3002 gel containing 1% IQP-0528, a nonnucleoside reverse transcriptase inhibitor (NNRTI), in rhesus macaques (RM). The gel (1.5 ml) was applied vaginally to 6 simian-human immunodeficiency (SHIV)-positive female RM. Blood, vaginal fluids, and rectal fluids were collected at 0, 1, 2, and 4 h. RM were euthanized at 4 h, and vaginal, cervical, rectal, and regional lymph node tissues were harvested. Anti-human immunodeficiency virus (HIV) activity was evaluated ex vivo by coculturing fresh or frozen vaginal tissues with activated human peripheral blood mononuclear cells (PBMCs) and measuring the p24 levels for 10 days after an HIV-1Ba-L challenge. The median levels of IQP-0528, determined using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) methods, were between 10(4) and 10(5) ng/g in vaginal and cervical tissue, between 10(3) and 10(4) ng/g in rectal tissues, and between 10(5) and 10(7) ng/ml in vaginal fluids over the 4-h period. The vaginal tissues protected the cocultured PBMCs from HIV-1 infection ex vivo, with a viral inhibition range of 81 to 100% in fresh and frozen tissues that were proximal, medial, and distal relative to the cervix. No viral inhibition was detected in untreated baseline tissues. Collectively, the median drug levels observed were 5 to 7 logs higher than the in vitro 50% effective concentration (EC50) range (0.21 ng/ml to 1.29 ng/ml), suggesting that 1.5 ml of the gel delivers IQP-0528 throughout the RM vaginal compartment at levels that are highly inhibitory to HIV-1. Importantly, antiviral activity was observed in both fresh and frozen vaginal tissues, broadening the scope of the ex vivo coculture model for future NNRTI efficacy studies.

Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis.

Intravaginal rings releasing tenofovir (TFV) or its prodrug, tenofovir disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal and immune cells. The exposure of vaginal epithelial or T cells to equimolar concentrations of radiolabeled TDF resulted in over 10-fold higher intracellular drug levels than exposure to TFV. Permeability studies demonstrated that TDF, but not TFV, entered cells by passive diffusion. TDF uptake was energy independent but its accumulation followed nonlinear kinetics, and excess unlabeled TDF inhibited radiolabeled TDF uptake in competition studies. The carboxylesterase inhibitor bis-nitrophenyl phosphate reduced TDF uptake, suggesting saturability of intracellular carboxylesterases. In contrast, although TFV uptake was energy dependent, no competition between unlabeled and radiolabeled TFV was observed, and the previously identified transporters, organic anion transporters (OATs) 1 and 3, were not expressed in human vaginal or T cells. The intracellular accumulation of TFV was reduced by the addition of endocytosis inhibitors, and this resulted in the loss of TFV antiviral activity. Kinetics of drug transport and metabolism were monitored by quantifying the parent drugs and their metabolites by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Results were consistent with the identified mechanisms of transport, and the exposure of vaginal epithelial cells to equimolar concentrations of TDF compared to TFV resulted in ∼40-fold higher levels of the active metabolite, tenofovir diphosphate. Together, these findings indicate that substantially lower concentrations of TDF than TFV are needed to protect cells from HIV and HSV-2.

Griffithsin protects mice from genital herpes by preventing cell-to-cell spread.

Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P < 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.

Network Meta-Analysis: Histologic and Histo-Endoscopic Improvement and Remission With Advanced Therapy in Ulcerative Colitis.

BACKGROUND: Histology has prognostic value in ulcerative colitis (UC). However, direct comparisons of histological endpoints are lacking. AIM: To perform a network meta-analysis (NMA) to compare histological endpoints with biologics and small molecules. METHODS: We searched four databases up until July 2024 for randomised controlled trials (RCTs) on advanced therapies for moderate-to-severe UC reporting histological endpoints. Outcomes included histological improvement or remission, and histo-endoscopic improvement after induction or during maintenance. We used a random-effects frequentist model and have reported outcomes as relative risk and 95% confidence interval. We estimated relative drug efficacy with the P-score. We conducted subgroup analysis by trial phase and evaluated risk of bias and evidence certainty. RESULTS: We included 24 RCTs (15 therapies, 8874 patients). Nineteen provided data on induction and 10 on maintenance; outcome definitions were similar. Etrasimod 2 mg/day ranked highest in achieving histologic improvement (P-score 0.98) and remission (P-score 0.90) following induction. Globally, guselkumab 200-400 mg ranked first for histo-endoscopic improvement, while etrasimod 2 mg/day and upadacitinib 45 mg/day were superior in the subgroup analysis. During maintenance, upadacitinib 30 mg/day was superior in achieving histologic improvement and remission (P-score 0.88 for both) and histo-endoscopic improvement (P-score 0.94). Etrasimod 2 mg/day ranked second for histologic remission (P-score 0.70) and histo-endoscopic improvement (P-score 0.73), while mirikizumab 200 mg/month ranked second for histologic improvement. CONCLUSION: These results support the ability of small molecules to achieve stringent endpoints in moderate-to-severe UC. Histological outcome data for biologics was sparser, particularly during maintenance. Head-to-head RCTs are imperative to better inform clinical practice.

Novel preclinical models of topical PrEP pharmacodynamics provide rationale for combination of drugs with complementary properties.

BACKGROUND: The limited success of recent HIV topical pre-exposure prophylaxis clinical trials highlights the need for more predictive models of drug efficacy that better simulate what may happen during sexual exposure. To address this gap, we developed complementary in vitro models to evaluate the ability of drugs to retain anti-HIV activity if cells were washed with seminal plasma (simulating what may happen following exposure to ejaculate), and to protect drug-naive T cells (representing newly recruited immune cells) co-cultured with explants that had been pretreated with drug. We focused on tenofovir disoproxil fumarate (TDF), the non-nucleoside reverse transcriptase inhibitors dapivirine (DPV) and IQP-0528, and the entry inhibitors maraviroc (MVC) and the D-peptide chol-PIE-12 trimer (PIE12). Studies were extended to macaques and the ability of cervical biopsies obtained from animals treated with an intravaginal ring formulation of IQP-0528 to protect ex vivo co-cultured T cells was determined. The antiviral activity of cervicovaginal lavage samples against a primary Clade C isolate was also measured and correlated with drug levels. RESULTS: Cells exposed to TDF were equally protected from HIV whether or not the drug-treated cells were washed with medium or seminal plasma prior to challenge. In contrast, several-fold higher concentrations of NNRTIs and entry inhibitors were needed to attain similar levels of HIV inhibition following a wash with seminal plasma. Conversely, the NNRTIs and PIE12, but not TDF or MVC, were effectively transferred from ex vivo treated explants and protected co-cultured T cells. Biopsies obtained from IQP-0528 ring-treated macaques also protected co-cultured T cells with viral inhibition ranging from 42-72%. Antiviral activity correlated with the concentration of drug recovered. Combinations of TDF with IQP-0528 protected in both in vitro models. CONCLUSIONS: Together, these models suggest that intracellularly retained drugs such as TDF may protect resident immune cells following coitus but sustained delivery may be required to protect immune cells subsequently recruited into the genital tract. Sustained delivery may also be critical for NNRTIs, which are rapidly transported out of cells and could be lost following sexual intercourse. An ideal approach may be a combination of drugs with complementary bioavailability profiles formulated for sustained delivery.

A microfluidic approach for label-free identification of small-sized microplastics in seawater.

Marine microplastics are emerging as a growing environmental concern due to their potential harm to marine biota. The substantial variations in their physical and chemical properties pose a significant challenge when it comes to sampling and characterizing small-sized microplastics. In this study, we introduce a novel microfluidic approach that simplifies the trapping and identification process of microplastics in surface seawater, eliminating the need for labeling. We examine various models, including support vector machine, random forest, convolutional neural network (CNN), and residual neural network (ResNet34), to assess their performance in identifying 11 common plastics. Our findings reveal that the CNN method outperforms the other models, achieving an impressive accuracy of 93% and a mean area under the curve of 98 ± 0.02%. Furthermore, we demonstrate that miniaturized devices can effectively trap and identify microplastics smaller than 50 µm. Overall, this proposed approach facilitates efficient sampling and identification of small-sized microplastics, potentially contributing to crucial long-term monitoring and treatment efforts.

Capsule Enteroscopy Using the Mirocam® versus OMOM® Systems: A Matched Case-Control Study.

Although several devices are available for small bowel capsule endoscopy, few studies have compared their visualization quality and diagnostic yield, despite users reporting subjective differences between them. This study aims to compare two widely used systems (Mirocam® MC1600 and OMOM® HD). Patients who underwent OMOM® HD capsule enteroscopy between August 2022 and February 2023 were prospectively included consecutively (cases). Controls were retrospectively selected from a database of patients who underwent Mirocam® MC1600 enteroscopy between March 2018 and July 2022 in a 1:1 ratio. Controls were matched for potential confounders (age, sex, indication, hospitalization, comorbidities, and opioid prescription). The small bowel cleanliness (global and divided by tertiles), the diagnostic yield (positive findings) and the transit times (TT) were compared. Overall, 214 patients were included (107:107). Global bowel preparation was similar between the OMOM® and Mirocam® groups. However, the average scores for each tertile were significantly higher when the OMOM® HD capsule was used (p < 0.05). Small bowel TT was shorter for OMOM® HD (265 ± 118 versus 307 ± 87 min, p = 0.020), while the diagnostic yield (55.0%) and relative distribution of lesions were similar. This study suggests that capsule characteristics, namely resolution, and illumination, systematically interfere with the perception of preparation quality. However, this did not affect the diagnostic yield.