Silicon photonic microresonator-based high-resolution line-by-line pulse shaping.

Optical pulse shaping stands as a formidable technique in ultrafast optics, radio-frequency photonics, and quantum communications. While existing systems rely on bulk optics or integrated platforms with planar waveguide sections for spatial dispersion, they face limitations in achieving finer (few- or sub-GHz) spectrum control. These methods either demand considerable space or suffer from pronounced phase errors and optical losses when assembled to achieve fine resolution. Addressing these challenges, we present a foundry-fabricated six-channel silicon photonic shaper using microresonator filter banks with inline phase control and high spectral resolution. Leveraging existing comb-based spectroscopic techniques, we devise a system to mitigate thermal crosstalk and enable the versatile use of our on-chip shaper. Our results demonstrate the shaper's ability to phase-compensate six comb lines at tunable channel spacings of 3, 4, and 5 GHz. Specifically, at a 3 GHz channel spacing, we showcase the generation of arbitrary waveforms in the time domain. This scalable design and control scheme holds promise in meeting future demands for high-precision spectral shaping capabilities.

Toxicity and Sublethal Effects of Piper hispidinervum Essential Oil on Behavioral and Physiological Responses of Sitophilus zeamais Populations.

This study aimed to evaluate the toxicity of Piper hispidinervum essential oil (PHEO) against 11 Brazilian populations of Sitophilus zeamais (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth (ri) of the insect populations were investigated. PHEO toxicity was determined through concentration-mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.00 to 1000.00 µL kg-1. Behavior was evaluated based on walking distance, walking time, walking speed, walking time proportion, flight height, and flight takeoff success. Respiration was measured via the respiratory rate, while population growth (ri) was assessed through the instantaneous growth rate. All 11 populations of S. zeamais were susceptible to PHEO, showing no signs of resistance. The populations exhibited varying behavioral and physiological responses to sublethal exposure to PHEO, indicating different mitigation strategies. The results confirm that PHEO possesses insecticidal potential for controlling S. zeamais populations. However, the observed behavioral and physiological responses should be considered when establishing control measures in pest management programs for stored products.

Self-sensitized photodegradation and adsorption of aqueous malachite green dye using one-dimensional titanium oxide nanofilaments.

Truly one-dimensional titanium oxide nanofilaments with a lepidocrocite structure (1DLs) were explored in the adsorption and photocatalytic degradation of aqueous malachite green (MG), a toxic polluting dye. Decolorization is monitored by ultraviolet-visible spectroscopy, and mineralization is confirmed by total organic carbon analysis. The 1DL/MG flocs are characterized by scanning electron microscopy and X-ray diffraction. 1DLs, a colloidal nanomaterial, exhibit flocculating behavior while demonstrating high affinity for MG, with a maximum uptake of >680 mg/g rapidly via ion exchange. Additionally, 1DLs decolorize MG under visible light only, unlike most available titania products, via a self-sensitization effect. MG is decolorized by 1DLs by >70% in 30 min under 1 sun exposure of visible light. Counterintuitively, dye adsorption increases as the normalized concentration by mass of 1DL decreases. Demonstrating high adsorption capacity and dye mineralization supports the use of 1DLs in water treatment and self-sensitization for photoelectrochemical devices, like solar cells.

Activation of the l-fucose utilization cluster in Campylobacter jejuni induces proteomic changes and enhances Caco-2 cell invasion and fibronectin binding.

Most Campylobacter jejuni isolates carry the fucose utilization cluster (Cj0480c-Cj0489) that supports the metabolism of l-fucose and d-arabinose. In this study we quantified l-fucose and d-arabinose metabolism and metabolite production, and the impact on Caco-2 cell interaction and binding to fibronectin, using C. jejuni NCTC11168 and the closely related human isolate C. jejuni strain 286. When cultured with l-fucose and d-arabinose, both isolates showed increased survival and production of acetate, pyruvate and succinate, and the respective signature metabolites lactate and glycolic acid, in line with an overall upregulation of l-fucose cluster proteins. In vitro Caco-2 cell studies and fibronectin-binding experiments showed a trend towards higher invasion and a significantly higher fibronectin binding efficacy of C. jejuni NCTC11168 cells grown with l-fucose and d-arabinose, while no significant differences were found with C. jejuni 286. Both fibronectin binding proteins, CadF and FlpA, were detected in the two isolates, but were not significantly differentially expressed in l-fucose or d-arabinose grown cells. Comparative proteomics analysis linked the C. jejuni NCTC11168 phenotypes uniquely to the more than 135-fold upregulated protein Cj0608, putative TolC-like component MacC, which, together with the detected Cj0606 and Cj0607 proteins, forms the tripartite secretion system MacABC with putative functions in antibiotic resistance, cell envelope stress response and virulence in Gram negative pathogenic bacteria. Further studies are required to elucidate the role of the MacABC system in C. jejuni cell surface structure modulation and virulence.

Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore? - A rapid scoping review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.

Autogenous Bilateral Cleft Alveolar Bone Grafting with rhBMP-2 and Cellular Bone Matrix.

Alveolar bone grafting (ABG) in bilateral cleft lip and palate (BCLP) patients provides a reconstructive challenge. We present a novel technique of combining autologous iliac crest bone graft (ICBG) with recombinant human bone morphogenic protein 2 (rhBMP-2) and cellular bone matrix (CBM) for ABG in BCLP patients. Complete bone fill occurred in 90% of patients, with 100% having bilateral canine eruption. No patients required repeat ABG, and no significant complications were reported. The alveolar cleft gap volume significantly decreased with an improvement of 75.87%. ABG with autologous ICBG with rhBMP-2 and CBM is an effective technique for patients with BCLP.

Bacterial reduction and temperature increase of titanium dental implant models treated with a 445 nm diode laser: an in vitro study.

In this in vitro study, the use of a 445 nm diode laser was investigated for the decontamination of titanium dental implants. Different irradiation protocols and the effect of repetitive laser irradiation on temperature increase and decontamination efficacy were evaluated on titanium implant models. An automated setup was developed to realize a scanning procedure for a full surface irradiation to recapitulate a clinical treatment. Three irradiation parameter sets A (continuous wave, power 0.8 W, duty cycle (DC) 100%, and 5 s), B (pulsed mode, DC 50%, power 1.0 W, and 10 s), and C (pulsed mode, DC 10%, power 3.0 W, and 20 s) were used to treat the rods for up to ten consecutive scans. The resulting temperature increase was measured by a thermal imaging camera and the decontamination efficacy of the procedures was evaluated against Escherichia coli and Staphylococcus aureus, and correlated with the applied laser fluence. An implant's temperature increase of 10 °C was set as the limit accepted in literature to avoid thermal damage to the surrounding tissue in vivo. Repeated irradiation of the specimens resulted in a steady increase in temperature. Parameter sets A and B caused a temperature increase of 11.27 ± 0.81 °C and 9.90 ± 0.37 °C after five consecutive laser scans, respectively, while parameter set C resulted in a temperature increase of only 8.20 ± 0.53 °C after ten surface scans. The microbiological study showed that all irradiation parameter sets achieved a complete bacterial reduction (99.9999% or 6-log10) after ten consecutive scans, however only parameter set C did not exceed the temperature threshold. A 445 nm diode laser can be used to decontaminate dental titanium rods, and repeated laser irradiation of the contaminated areas increases the antimicrobial effect of the treatment; however, the correct choice of parameters is needed to provide adequate laser fluence while preventing an implant's temperature increase that could cause damage to the surrounding tissue.

Sound-seeking before and after hearing loss in mice.

How we move our bodies affects how we perceive sound. For instance, head movements help us to better localize the source of a sound and to compensate for asymmetric hearing loss. However, many auditory experiments are designed to restrict head and body movements. To study the role of movement in hearing, we developed a behavioral task called sound-seeking that rewarded freely moving mice for tracking down an ongoing sound source. Over the course of learning, mice more efficiently navigated to the sound. Next, we asked how sound-seeking was affected by hearing loss induced by surgical removal of the malleus from the middle ear. After bilateral hearing loss sound-seeking performance drastically declined and did not recover. In striking contrast, after unilateral hearing loss mice were only transiently impaired and then recovered their sound-seek ability over about a week. Throughout recovery, unilateral mice increasingly relied on a movement strategy of sequentially checking potential locations for the sound source. In contrast, the startle reflex (an innate auditory behavior) was preserved after unilateral hearing loss and abolished by bilateral hearing loss without recovery over time. In sum, mice compensate with body movement for permanent unilateral damage to the peripheral auditory system. Looking forward, this paradigm provides an opportunity to examine how movement enhances perception and enables resilient adaptation to sensory disorders.

Racial Disparities in Pulse Oximetry, in COVID-19 and ICU Settings.

OBJECTIVES BACKGROUND: This study aimed to assess the impact of race on pulse oximetry reliability, taking into account Spo2 ranges, COVID-19 diagnosis, and ICU admission. DESIGN: Retrospective cohort study covering admissions from January 2020 to April 2024. SETTING: National COVID Cohort Collaborative (N3C) database, consisting of electronic health records from 80 U.S. institutions. PATIENTS/SUBJECTS: Patients were selected from the N3C database based on the availability of data on self-identified race and both pulse oximetry estimated Spo2 and Sao2. Subgroups included patients in ICU and non-ICU settings, with or without a diagnosis of COVID-19 disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The agreement between Spo2 and Sao2 was assessed across racial groups (American Indian or Alaska Native, Asian, Black, Hispanic or Latino, Pacific Islander, and White). Each patient's initial Sao2 measurement was matched with the closest Spo2 values recorded within the preceding 10-minute time frame. The risk of hidden hypoxemia (Spo2 ≥ 88% but Sao2 < 88%) was determined for various Spo2 ranges, races, and clinical scenarios. We used a generalized logistic mixed-effects model to evaluate the impact of relevant variables, such as COVID-19, ICU admission, age, sex, race, and Spo2, on the risk of hidden hypoxemia, while accounting for the random effects within each hospital. A total of 80,541 patients were included, consisting of 596 American Indian or Alaska Native, 2,729 Asian, 11,889 Black, 13,154 Hispanic or Latino, 221 Pacific Islander, and 51,952 White individuals. Discrepancies between Spo2 and Sao2 were observed across all racial groups, with the most pronounced bias in Black patients. Hidden hypoxemia rates were higher in Black patients across all Spo2 subgroups, for all clinical scenarios. The odds of hidden hypoxemia were higher for Black and Hispanic or Latino patients and for those with COVID-19 disease. CONCLUSIONS: Race significantly impacts pulse oximetry reliability. Not only Black and Hispanic or Latino patients were at higher risk for hidden hypoxemia, but also those admitted with a COVID-19 diagnosis. Future in-depth explorations into the underlying causes and potential solutions are needed.

Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.

Digital Exclusion, Social Deprivation, and Clinical Outcomes of Patients Undergoing Hyperacuity Home Monitoring.

INTRODUCTION: Digital exclusion is a growing challenge when deploying digital patient care pathways and a potential barrier to widespread implementation, especially in the field of smartphone-based self-monitoring of vision. This retrospective case series seeks to examine the characteristics of individuals who adhere to a smartphone home monitoring programme using the Alleye app for retinal disease, with a focus on digital exclusion, social deprivation and clinical outcomes. METHODS: We conducted a retrospective analysis of 89 patients with retinal pathologies including diabetic retinopathy and retinal vein occlusions at Moorfields Eye Hospital participating in an Alleye home monitoring programme between April 2020 and November 2022. Postcodes were used to determine the Digital Exclusion Risk Index (DERI) and the Index of Multiple Deprivation (IMD) rebased for London. Clinical information from the electronic patient record and Alleye app usage data were extracted for each patient. Associations between the DERI/IMD, clinical parameters and app use were examined using multivariable regression models. RESULTS: Mean DERI was 2.56 (standard deviation [SD] = 0.36), IMD was 6.25 (SD = 2.79), visual acuity (VA) in the better eye at study entry was 83.28 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (SD = 7.92), and mean follow-up was 344.46 days (SD = 260.13). During the observation period, 36% received an intravitreal injection (IVI) and VA fell by at least ten letters in approximately one in four patients. In 87.5% of patients requiring IVI, the use of the app increased. We found no association between clinical parameters and programme adherence for DERI or IMD. CONCLUSIONS: We found no association between high digital exclusion risk and high social deprivation with monitoring adherence to smartphone-based self-monitoring of vision, contrary to the currently available evidence. This suggests that smartphone-based self-monitoring of vision is accessible to population groups of varying digital exclusion and social deprivation risk, and can be safely employed to monitor clinical progression.

The Effect of Barrel-Stave Osteotomy Length in Sagittal Strip Craniectomy.

OBJECTIVE: In managing sagittal craniosynostosis, strip craniectomy of the affected suture is commonly paired with barrel-stave osteotomies to allow for additional cranial remodeling. However, the effect of these osteotomies is not well-established. This study aimed to evaluate the effect of the length of barrel-stave osteotomies on outcomes in patients with sagittal craniosynostosis. DESIGN: A retrospective review of operative records and pre-operative and one-year post-operative three-dimensional images. SETTING: Tertiary care pediatric institution. PATIENTS: Forty-five patients with sagittal craniosynostosis. INTERVENTIONS: Sagittal strip craniectomy and either long, medium, or short barrel-stave osteotomy lengths followed by helmet therapy. MAIN OUTCOME MEASURES: Operative and three-dimensional craniometric outcomes. RESULTS: Operative time, estimated blood loss, and hospital length of stay were significantly decreased in the short group (P = .003; 0.002; 0.027). The cranial index was normalized in all groups, but the long group was significantly lower (P = .007; 0.025). Head circumference was similar between groups. All indexes were within the normal percentiles in all groups. The medium group had a significantly decreased scaphocephalic index (P = .031; .035). The short group had significantly greater occipital bulleting than the medium group (P = .001). The long group had significantly greater narrowing than the short group (P = .036). CONCLUSIONS: Strip craniectomy with the addition of long, medium, or short barrel staves all resulted in clinically successful outcomes. Our findings suggest that increased barrel-stave osteotomy length may not be necessary for a successful outcome while avoiding more extensive dissection, potential risk, increased operative time, and hospital length of stay.

Use of Cosmetics in Pregnancy and Neurotoxicity: Can It Increase the Risk of Congenital Enteric Neuropathies?

Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.

Role of Inflammation and the NF-κB Signaling Pathway in Hirschsprung's Disease.

Hirschsprung's disease (HSCR, incidence 1/5000 live births) is caused by the failure of neural crest-derived precursors to migrate, survive, proliferate, or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, including inflammatory processes. The NF-κB family controls several biological processes, including inflammation, neurogenesis, and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided into ganglionic and aganglionic segments). We found decreased gene expression of the NF-κB main subunit RELA but also of NFKBIA, TNFA, TFGBR2, and ERBB3 in the pathologic distal aganglionic segments compared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA/p65 in the aganglionic distal segments by immunofluorescence staining. Further, we show that the expression of RelA/p65 protein in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. All in all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological effects of HSCR.

Improving the Tribological Performance of POM through the Incorporation of Bio-Based Materials.

Polyoxymethylene (POM), an engineering polymer commonly used in tribological applications, is often reinforced with fossil-based fibers such as carbon and/or glass fibers to improve its properties. To find more sustainable solutions, in this study, the tribological performance of POM/short cellulose fiber composites at different sliding conditions is investigated. An improvement in the wear coefficient of roughly 69% is observed at the harshest conditions of 5 MPa and 1 m · s-1 with only 10 wt.% cellulose fibers. The friction behavior is furthermore stabilized through fiber addition, as the unfilled polymer did not show a steady state. No signs of thermo-oxidative degradation are found after tribological testing. This study presents promising results for sustainable wear-resistant polymer materials in tribological applications.

Patterns and Risk Factors for Rehospitalizations Within the First 90 Days Following Discharge After Heart Transplantation.

BACKGROUND: Heart transplantation (HT) recipients are at risk for urgent rehospitalizations following discharge. However, data on prevalence, risk factors and clinical outcomes associated with post-HT rehospitalization are limited. METHODS: This study aims to describe patterns of urgent rehospitalizations in HT recipients at a cardiology reference center in Brazil. Rehospitalizations and deaths occurring within the first 90 days following hospital discharge were identified. Regression models were used to identify variables associated with urgent rehospitalizations. RESULTS: A total of 239 patients were included. Of those, 118 (49.4%) presented with a rehospitalization within 90 days following hospital discharge and 5 (2.01%) died. Most patients who were rehospitalized had one new hospital admission (86.0%). The main cause of urgent rehospitalization was infection (55.0%). In the multivariate analysis, elevated C-reactive protein at discharge and the occurrence of intracranial bleeding at index hospitalization were associated with an increased risk of readmission. Longer duration of index hospitalization and use of lower doses of azathioprine were associated with a lower risk of rehospitalization. CONCLUSION: Around half of HT recipients were rehospitalized within the first 90 days after hospital discharge. Understanding factors associated with post-HT rehospitalization may help the implementation of strategies to avoid patient morbidity and hospital costs.

Hepatic stearoyl-CoA desaturase-1 deficiency induces fibrosis and hepatocellular carcinoma-related gene activation under a high carbohydrate low fat diet.

Stearoyl-CoA desaturase-1 (SCD1) is a pivotal enzyme in lipogenesis, which catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids, whose ablation downregulates lipid synthesis, preventing steatosis and obesity. Yet deletion of SCD1 promotes hepatic inflammation and endoplasmic reticulum stress, raising the question of whether hepatic SCD1 deficiency promotes further liver damage, including fibrosis. To delineate whether SCD1 deficiency predisposes the liver to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), we employed in vivo SCD1 deficient global and liver-specific mouse models fed a high carbohydrate low-fat diet and in vitro established AML12 mouse cells. The absence of liver SCD1 remarkably increased the saturation of liver lipid species, as indicated by lipidomic analysis, and led to hepatic fibrosis. Consistently, SCD1 deficiency promoted hepatic gene expression related to fibrosis, cirrhosis, and HCC. Deletion of SCD1 increased the circulating levels of Osteopontin, known to be increased in fibrosis, and alpha-fetoprotein, often used as an early marker and a prognostic marker for patients with HCC. De novo lipogenesis or dietary supplementation of oleate, an SCD1-generated MUFA, restored the gene expression related to fibrosis, cirrhosis, and HCC. Although SCD1 deficient mice are protected against obesity and fatty liver, our results show that MUFA deprivation results in liver injury, including fibrosis, thus providing novel insights between MUFA insufficiency and pathways leading to fibrosis, cirrhosis, and HCC under lean non-steatotic conditions.

An essential host dietary fatty acid promotes TcpH inhibition of TcpP proteolysis promoting virulence gene expression in Vibrio cholerae.

Vibrio cholerae is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated pilus, is regulated directly by ToxT and indirectly by two transmembrane transcription regulators (TTRs), ToxR and TcpP, that promote the expression of toxT. TcpP abundance and activity are controlled by TcpH, a single-pass transmembrane protein, which protects TcpP from a two-step proteolytic process known as regulated intramembrane proteolysis (RIP). The mechanism of TcpH-mediated protection of TcpP represents a major gap in our understanding of V. cholerae pathogenesis. The absence of tcpH leads to unimpeded degradation of TcpP in vitro and a colonization defect in a neonate mouse model of V. cholerae colonization. Here, we show that TcpH protects TcpP from RIP via direct interaction. We also demonstrate that α-linolenic acid, a dietary fatty acid, promotes TcpH-dependent inhibition of RIP via co-association of TcpP and TcpH molecules within detergent-resistant membranes (DRMs) in a mechanism requiring the TcpH transmembrane domain. Taken together, our data support a model where V. cholerae cells use exogenous α-linolenic acid to remodel the phospholipid bilayer in vivo, leading to co-association of TcpP and TcpH within DRMs where RIP of TcpP is inhibited by TcpH, thereby promoting V. cholerae pathogenicity. IMPORTANCE: Vibrio cholerae continues to pose a significant global burden on health and an alternative therapeutic approach is needed, due to evolving multidrug resistance strains. Transcription of toxT, stimulated by TcpP and ToxR, is essential for V. cholerae pathogenesis. Our results show that TcpP, one of the major regulators of toxT gene expression, is protected from proteolysis by TcpH, via direct interaction. Furthermore, we identified a gut metabolite, α-linolenic acid, that stimulates the co-association of TcpP and TcpH within detergent-resistant membranes (also known as lipid-ordered membrane domains), thereby supporting TcpH-dependent antagonism of TcpP proteolysis. Data presented here extend our knowledge of RIP, virulence gene regulation in V. cholerae, and, to the best of our knowledge, provides the first evidence that lipid-ordered membranes exist within V. cholerae. The model presented here also suggests that TTRs, common among bacteria and archaea, and co-component signal transduction systems present in Enterobacteria, could also be influenced similarly.

Double-Arc Slow-Coagulation Transscleral Cyclophotocoagulation Laser Protocol: One-Year Effectiveness and Safety Outcomes.

PURPOSE: To report the short-term effectiveness and safety results of a new continuous laser protocol, double-arc slow-coagulation transscleral cyclophotocoagulation (DA-TSCPC). DESIGN: Multicenter retrospective study. PARTICIPANTS: We reviewed the clinical records of refractory glaucoma patients that had undergone DA-TSCPC between April 2019 and July 2022, with at least 12 months of postoperative follow-up. METHODS: The technique was standardized (energy: 1400 mW; duration: 4 seconds; 28 applications). The applications were divided into 2 rows (upper and lower arcs). For each arc, 7 spots were applied over the ciliary body shadow and 7 spots 1.5 mm behind, sparing the 3 and 9 o'clock meridians. MAIN OUTCOME MEASURES: Success was defined as postoperative intraocular pressure (IOP) between 6 and 18 mmHg and an IOP reduction of 30% (without oral acetazolamide). For eyes with no light perception (NLP), in which treatment goal was pain relief, success was defined as a 30% IOP reduction and no pain (without oral acetazolamide). Patients were divided according to visual acuity: ≥ 20/400 (group 1) and < 20/400 (group 2). RESULTS: Ninety eyes of 90 patients (mean age: 61 ± 15 years) were included. Glaucoma diagnosis frequency was: neovascular glaucoma (38%), open-angle glaucoma (28%), silicone oil secondary glaucoma (17%), and others (18%). Overall, the mean IOP was significantly reduced from 35 ± 12 to 22 ± 14 mmHg (P < 0.01) at the last follow-up visit. The number of hypotensive eye drops (2.6 ± 1-2.3 ± 1; P = 0.02) and the use of oral acetazolamide (61%-11%; P < 0.01) were also reduced. Kaplan-Meier survival analysis revealed a global success rate of 65.6% after 12 months. A higher success rate was found for group 1 (78.6%) compared to group 2 (59.6%; P = 0.047; logrank test). The main complications observed were corneal ulcer (4.4%), macular edema (1.1%), and hyphema (1.1%). Among the 26 eyes with NLP, 65% achieved success criteria at 12 months and 2 (7.7%) developed phthisis. CONCLUSIONS: Based on these initial retrospective data, the DA-TSCPC protocol seems to be an alternative for refractory glaucoma management, presenting significant IOP reduction and a good safety profile after 1 year. Better outcomes were observed in eyes with less severe functional damage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.