An Azospirillum brasilense chemoreceptor that mediates nitrate chemotaxis has conditional roles in the colonization of plant roots.

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium Azospirillum brasilense. We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of tlp2 is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.IMPORTANCEBacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere.

Human Immunodeficiency Virus in Older Adults.

As people with HIV live longer, they can experience increased incidence and earlier onset of chronic conditions and geriatric syndromes. Older people are also at substantially increased risk of delayed diagnosis and treatment for HIV. Increasing provider awareness of this is pivotal in ensuring adequate consideration of HIV testing and earlier screening for chronic conditions. In addition, evaluating patients for common geriatric syndromes such as polypharmacy, frailty, falls, and cognitive impairment should be contextualized based on how they present.

Evaluation of the Efficiency of a Digital Workflow for Cataract Planning in Patients with Astigmatism.

Purpose: To evaluate the efficiency and associated costs of a digital cataract workflow system and manual cataract workflow system for patients, with astigmatism presenting for cataract surgery in Brisbane, Australia. Patients and Methods: Sixty patients with bilateral cataract requiring toric intraocular lenses (IOL) were sequentially assigned to a manual cataract workflow (n = 30) or digital workflow (n = 30) using EQ Workplace (SW v1.7.0) running on FORUM (SW v.4.2.1.66) (Carl Zeiss Meditec, Jena, Germany). Each step of preoperative data acquisition and analysis was timed. Steps in each workflow were divided into presurgical planning time and total workflow time, the latter including the time required to input toric data into CALLISTO eye (Carl Zeiss Meditec). Secondary outcomes included staff costs within each workflow. Results: Median presurgical planning time using a digital workflow process was 6.51 ± 0.65 minutes, and using a manual workflow process, 12.32 ± 0.56 minutes (p < 0.001). Similarly, median total workflow time using a digital workflow process was 6.93 ± 0.57 minutes and using a manual workflow process, 13.49 ± 0.47 minutes (p < 0.001). Evaluating the staff remuneration during presurgical planning and the operating costs associated with running EQ Workplace, there was a cost-reduction of 35% per patient when using the digital cataract workflow process. Conclusion: Using a digital cataract workflow process is more efficient and provides staff cost-savings compared to a manual workflow process when planning for toric IOL implantation.

The prevalence of both cataracts and cataract surgery is known to be increasing in Australia and other economically developed countries. During cataract surgery, an individual's natural lens is removed, and an artificial lens (known as an intraocular lens or IOL) is inserted. Many patients elect to correct their astigmatism at the time of their cataract surgery by choosing to have a specific type of IOL, called a toric lens, implanted, which should reduce their dependence on spectacles following surgery. Ophthalmology clinics and clinical staff can spend significant time accurately planning and selecting a toric IOL in preparation for surgery. We evaluated the time spent on toric IOL planning in a digital workflow versus a manual workflow. There was a significant reduction in time (and therefore reduced staffing costs) with the digital workflow. Digital workflows offer improved efficiency and can be more cost-effective, both of which are important when meeting the increasing demands and rates of cataract surgery.

Associations between lipid abnormalities and diabetic retinopathy across a large United States national database.

BACKGROUND/OBJECTIVES: While dyslipidaemia has been suggested as a potential risk factor for diabetic retinopathy (DR), previous studies have reported conflicting findings. This study aimed to better characterize the relationship between abnormal serum levels of various lipid markers and the risk of the development and progression of DR. SUBJECTS/METHODS: This retrospective cohort study utilized a United States national database of electronic medical records. Adults with a history of type 2 diabetes mellitus without type 1 diabetes mellitus were divided into cohorts based on the presence of abnormal serum levels of various lipid markers. Propensity score matching was performed to match cohorts with abnormal lipid levels to those with normal lipid levels on covariates. The cohorts were then compared to evaluate the hazard ratios (HR) of receiving a new DR diagnosis, pars plana vitrectomy, panretinal photocoagulation, vitreous haemorrhage, proliferative diabetic retinopathy, diabetic macular oedema (DMO), and traction retinal detachment. RESULTS: The database contained 1,126,231 eligible patients (mean age: 60.8 [14.2] years; 46.0% female). Among patients without prior DR, low HDL (HR = 0.94, CI = 0.90-0.98), total cholesterol (HR = 0.88, CI = 0.85-0.91), and high triglyceride (HR = 0.91, CI = 0.86-0.97) levels were associated with a decreased risk of receiving a DR diagnosis. Among patients with preexisting DR, high LDL levels was associated with an increased risk of DMO (HR = 1.42, CI = 1.15-1.75), whereas low HDL levels was associated with a marginally decreased risk (HR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Elevated levels of markers of dyslipidaemia are inversely associated with the risk of receiving a DR diagnosis, but this relationship is blunted after the onset of DR.

Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database.

BACKGROUND/OBJECTIVES: Bariatric surgery, as indicated for treatment of morbid obesity, has been studied in association with short term effects on ocular pathology. However, effects of surgery on postoperative disease incidence is largely unknown. SUBJECTS/METHODS: In this retrospective cohort study, the TriNetX United States Collaborative Network national database, was queried for patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery. Patients were propensity score matched across baseline demographics at the time of surgery and compared to those presenting with an ICD10 code for morbid obesity with no records of a procedural code for bariatric surgery, identifying 42,408 patients per cohort. New diagnoses or procedural codes found after the surgical index date for diabetic retinopathy, age-related macular degeneration, glaucoma, low vision, and blindness along with pertinent treatment metrics were monitored. RESULTS: Bariatric surgery was found to be associated with reduced future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319), macular edema (RR: 0.224; 95% CI: 0.170-0.297), vitreous hemorrhage (RR: 0.459; 95% CI: 0.323-0.653), ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487), glaucoma (RR: 0.360; 95% CI: 0.326-0.399), use of ocular pressure lowering medications (RR: 0.565; 95% CI: 0.496-0.644), age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882), cataract surgery (RR: 0.524; 95% CI: 0.448-0.612), and low vision and blindness (RR: 0.328; 95% CI: 0.294-0.365) compared to patients not surgically managed. CONCLUSIONS: The present analysis comprising a large US cohort of patients suggests that bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality.

Retrospective Cohort Study of Sickle Cell Disease and Large Vessel Retinal Vascular Occlusion Risk in a National US Database.

OBJECTIVE: To determine if differences exist in the risk of developing large vessel retinal vascular occlusions in patients with sickle cell states. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with sickle cell disease or trait evaluated by an ophthalmologist were compared to matched controls without sickle cell disease or trait also evaluated by an ophthalmologist. METHODS: This study used deidentified data from a national database (2006-2024), using International Classification of Diseases 10 codes to select for retinal vascular occlusions. Propensity score matching was performed with respect to age, sex, race, ethnicity, smoking, hypertension, diabetes, dyslipidemias, and obesity, resulting in HbSS, HbSC, and sickle cell trait (SCT) cohorts and matched control cohorts. MAIN OUTCOME MEASURES: Risk ratios and 95% confidence intervals (CI) of retinal vascular occlusion diagnosis, including central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), central retinal venous occlusion (CRVO), branch retinal venous occlusion (BRVO), and corneal dystrophy as a negative control, given sickle cell disease or trait. RESULTS: After propensity score matching, HbSS (n=10,802, mean ± standard deviation age of 38.6 ± 20.6 years), HbSC (n=4,296, 34.3 ± 17.8 years), and SCT (n=15,249, 39.8 ± 23.7 years) cohorts were compared to control cohorts (n=10,802, 38.7 ± 20.7 years; n=4,296, 34.6 ± 18.0 years; n=15,249, 39.9 ± 23.8 years, respectively). Patients with sickle cell disease (HbSS) had higher risk of developing any retinal vascular occlusion (RR 2.33; 95% CI 1.82-3.00), CRAO (RR 2.71; 95% CI 1.65-4.47) and BRAO (RR 4.90; 95% CI 2.48-9.67) than matched controls. Patients with HbSC disease had higher risk (RR 3.14; 95% CI 1.95-5.06) of developing any retinal vascular occlusion than matched controls without sickle cell disease. Patients with sickle cell trait did not have higher risk of developing retinal vascular occlusions (RR 1.01; 95% CI 0.81-1.26) than matched controls. CONCLUSIONS: In a retrospective cohort study, patients with HbSS sickle cell disease have an increased risk of developing retinal vascular occlusions, and more specifically CRAO and BRAO compared to patients without sickle cell disease.

Long-Term Visual Outcomes in Patients With Idiopathic Epiretinal Membrane Surgery.

BACKGROUND AND OBJECTIVE: Our aim was to assess long-term outcomes following surgical repair of idiopathic epiretinal membrane (ERM) with pars plana vitrectomy (PPV) and membrane peel (MP). PATIENTS AND METHODS: A retrospective study evaluated patients with idiopathic ERM who underwent surgical repair at a single academic tertiary center with five to nine years of postoperative follow-up, assessing preoperative characteristics, surgical techniques, best visual acuity (BVA), and optical coherence tomography biomarkers at various time points. RESULTS: The study involved 67 patients (72 eyes) with an average postoperative follow-up of 82.8 ± 18.8 months. Patients with cone outer segment tips integrity at initial presentation and 1-year follow-up and patients with external limiting membrane and ellipsoid zone integrity at 1-year follow-up were noted to have significantly better long-term visual acuity than those without. More than 85% of patients achieved a BVA > 70 seven years after surgical repair. CONCLUSIONS: Vitreoretinal surgery for idiopathic ERM resulted in improved anatomical recovery and sustained visual acuity gain over long-term follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:70-77.].

Influence of Four Veterinary Antibiotics on Constructed Treatment Wetland Nitrogen Transformation.

The use of wetlands as a treatment approach for nitrogen in runoff is a common practice in agroecosystems. However, nitrate is not the sole constituent present in agricultural runoff and other biologically active contaminants have the potential to affect nitrate removal efficiency. In this study, the impacts of the combined effects of four common veterinary antibiotics (chlortetracycline, sulfamethazine, lincomycin, monensin) on nitrate-N treatment efficiency in saturated sediments and wetlands were evaluated in a coupled microcosm/mesocosm scale experiment. Veterinary antibiotics were hypothesized to significantly impact nitrogen speciation (e.g., nitrate and ammonium) and nitrogen uptake and transformation processes (e.g., plant uptake and denitrification) within the wetland ecosystems. To test this hypothesis, the coupled study had three objectives: 1. assess veterinary antibiotic impact on nitrogen cycle processes in wetland sediments using microcosm incubations, 2. measure nitrate-N reduction in water of floating treatment wetland systems over time following the introduction of veterinary antibiotic residues, and 3. identify the fate of veterinary antibiotics in floating treatment wetlands using mesocosms. Microcosms containing added mixtures of the veterinary antibiotics had little to no effect at lower concentrations but stimulated denitrification potential rates at higher concentrations. Based on observed changes in the nitrogen loss in the microcosm experiments, floating treatment wetland mesocosms were enriched with 1000 µg L-1 of the antibiotic mixture. Rates of nitrate-N loss observed in mesocosms with the veterinary antibiotic enrichment were consistent with the microcosm experiments in that denitrification was not inhibited, even at the high dosage. In the mesocosm experiments, average nitrate-N removal rates were not found to be impacted by the veterinary antibiotics. Further, veterinary antibiotics were primarily found in the roots of the floating treatment wetland biomass, accumulating approximately 190 mg m-2 of the antibiotic mixture. These findings provide new insight into the impact that veterinary antibiotic mixtures may have on nutrient management strategies for large-scale agricultural operations and the potential for veterinary antibiotic removal in these wetlands.

Transcutaneous Retrobulbar Amphotericin B Injection for Invasive Fungal Sinusitis with Orbital Involvement: A Systematic Review.

BACKGROUND: Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration of amphotericin B (TRAMB) is an off-label adjunctive treatment that can increase drug penetrance into diseased orbital tissue. To date, there is a lack of consensus regarding the use of TRAMB for treatment of IFS with orbital involvement. OBJECTIVE: This systematic review aims to synthesize the indications, efficacy, and potential complications of TRAMB. METHODS: PubMed, EMBASE, and Web of Science databases were probed for systematic review. Article search was conducted through June 2023 using the keywords "invasive fungal sinusitis," "invasive fungal rhinosinusitis," "rhino-orbital mucormycosis," "rhinosinusitis," "orbital," "retrobulbar," and "amphotericin." RESULTS: In suitable cases as determined by radiologic and clinical evaluation, TRAMB administration has the potential to improve orbital salvage rates and improve versus stabilize visual acuity. Treatment complications are more likely with deoxycholate than with liposomal amphotericin formulations. The existing literature describing use of TRAMB is limited due to its retrospective nature, but the increase in IFS cases since 2020 due to the COVID pandemic has broadened the literature. CONCLUSIONS: TRAMB is an effective adjunctive treatment in IFS with mild-to-moderate orbital involvement when used in combination with standard of care debridement, systemic antifungal therapy, and immunosuppression reversal. Prospective longitudinal studies and multi-institutional randomized trials are necessary to determine the definitive utility of TRAMB.

Evidence for the Hepato-Retinal Axis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Liver health has been reported to be associated with retinal pathology in various ways. These include deposition of retino-toxins, neovascular drive, and disruption of the blood-retina barrier. Extrahepatic synthesis of implicated molecules and hemodynamic changes in liver dysfunction are also considered. The objective was to review the current evidence for and against a hepato-retinal axis that may guide further areas of preclinical and clinical investigation. METHODS: This was a systematic review. PubMed and Cochrane were queried for English language studies examining the connection between hepatic dysfunction and retinal pathology. RESULTS: Fourteen studies were included and examined out of 604 candidate publications. The studies selected include preclinical studies as well as clinical case series and studies. CONCLUSIONS: Several liver pathologies may be linked to retinal pathology as mediated by hepatically synthesized molecules. The hepato-retinal axis may be present and further, targeted studies of the axis are warranted. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Youth mental health care use during the COVID-19 pandemic in Alberta, Canada: an interrupted time series, population-based study.

BACKGROUND: During the COVID-19 pandemic, youth had rising mental health needs and changes in service accessibility. Our study investigated changes in use of mental health care services for Canadian youth in Alberta before and during the COVID-19 pandemic. We also investigated how youth utilization patterns differed for subgroups based on social factors (i.e., age, gender, socioeconomic status, and geography) previously associated with health care access. METHODS: We used cross-sectional population-based data from Alberta, Canada to understand youth (15-24 year) mental health care use from 2018/19 to 2021/22. We performed interrupted time series design, segmented regression modeling on type of mental health care use (i.e., general physician, psychiatrist, emergency room, and hospitalization) and diagnosis-related use. We also investigated the characteristics of youth who utilized mental health care services and stratified diagnosis-related use patterns by youth subgroups. RESULTS: The proportion of youth using mental health care significantly increased from 15.6% in 2018/19 to 18.8% in 2021/22. Mental health care use showed an immediate drop in April 2020 when the COVID-19 pandemic was declared and public health protections were instituted, followed by a steady rise during the next 2 years. An increase was significant for general physician and psychiatrist visits. Most individual diagnoses included in this study showed significant increasing trends during the pandemic (i.e., anxiety, adjustment, ADHD, schizophrenia, and self-harm), with substance use showing an overall decrease. Mortality rates greatly increased for youth being seen for mental health reasons from 71 per 100,000 youth in 2018/19 to 163 per 100,000 in 2021/22. In addition, there were clear shifts over time in the characteristics of youth using mental health care services. Specifically, there was increased utilization for women/girls compared to men/boys and for youth from wealthier neighborhoods. Increases over time in the utilization of services for self-harm were limited to younger youth (15-16 year). CONCLUSIONS: The study provides evidence of shifts in mental health care use during the COVID-19 pandemic. Findings can be used to plan for ongoing mental health needs of youth, future pandemic responses, and other public health emergencies.

Metastable States in the Hinge-Bending Landscape of an Enzyme in an Atomistic Cytoplasm Simulation.

Many enzymes undergo major conformational changes to function in cells, particularly when they bind to more than one substrate. We quantify the large-amplitude hinge-bending landscape of human phosphoglycerate kinase (PGK) in a human cytoplasm. Approximately 70 µs of all-atom simulations, upon coarse graining, reveal three metastable states of PGK with different hinge angle distributions and additional substates. The "open" state was more populated than the "semi-open" or "closed" states. In addition to free energies and barriers within the landscape, we characterized the average transition state passage time of ≈0.3 µs and reversible substrate and product binding. Human PGK in a dilute solution simulation shows a transition directly from the open to closed states, in agreement with previous SAXS experiments, suggesting that the cell-like model environment promotes stability of the human PGK semi-open state. Yeast PGK also sampled three metastable states within the cytoplasm model, with the closed state favored in our simulation.

Characterization and prevalence of ocular comorbidities and risk of legal blindness across the United States.

BACKGROUND/OBJECTIVES: Vision loss is a top disability in the United States (US). Patients commonly present with multiple ocular diseases, but the extent to which this places them at risk for vision loss, and if sex and race impacts this, is poorly understood. This exploratory analysis evaluated which ocular comorbidities and demographics are at highest risk for visual impairment. SUBJECTS/METHODS: A retrospective cross-sectional study was conducted through the TriNetX Analytics Network, an aggregated network encompassing over 90 million insured and uninsured patients across 50 healthcare organizations from all regions in the US. Patients with diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), glaucoma, and uveitis were included in this study. Ocular diseases and visual impairment were determined through ICD-10 codes. Prevalence and odds ratios were calculated while stratifying by sex and racial demographics. Statistical analyses were completed using RStudio and Excel with 95% confidence intervals calculated. RESULTS: The comorbid conditions with the highest prevalence of visual impairment were uveitis and RVO (39.94%), uveitis and neovascular AMD (37.61%), and uveitis and glaucoma (33.23%). The comorbidity with the highest odds for visual impairment was uveitis and RVO (POR 4.86; 95% CI 4.49, 5.26). Compared to white males, Black and Hispanic males were disproportionately affected by visual impairment across ocular comorbidities. CONCLUSION: This study quantified the prevalence and odds of visual impairment for unilateral and comorbid ocular disease, with the addition of uveitis causing the greatest increase. Black and Hispanic males were disproportionately affected by visual impairment across comorbid conditions.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.