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.

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.

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.

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.

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.

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.

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.

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.

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.

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.].

Tracking 20 years of forest demographics in east Texas, USA, using national forest inventory data.

Forest resource reporting techniques primarily use the two most recent measurements for understanding forest change. Multiple remeasurements now exist within the US national forest inventory (NFI), providing an opportunity to examine long-term forest demographics. We leverage two decades of remeasurements to quantify live-dead wood demographics which can better inform estimates of resource changes in forest ecosystems. Our overall objective is to identify opportunities and gaps in tracking 20 years of forest demographics within the US NFI using east Texas as a pilot study region given its diversity of tree species, prevalence of managed conditions, frequency of disturbances, and relatively rapid change driven by a warm, humid climate. We examine growth and mortality rates, identify transitions to downed dead wood/litter and removal via harvest, and describe implications of these processes focusing on key species groups (i.e., loblolly pine, post oak, and water oak) and size classes (i.e., saplings, small and large trees). Growth and mortality rates fluctuated differently over time by species and stem sizes in response to large-scale disturbances, namely the 2011 drought in Texas. Tree-fall rates were highest in saplings and snag-fall rates trended higher in smaller trees. For removal rates, different stem sizes generally followed similar patterns within each species group. Forest demographics from the field-based US NFI are informative for identifying diffuse lagged mortality, species- and size-specific effects, and management effects. Moreover, researchers continually seek to employ ancillary data and develop new statistical methods to enhance understanding of forest resource changes from field-based inventories.

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort.

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. RESULTS: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. CONCLUSION: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:626-633.].

Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.

Lack of association between Lp(a) and retinal vein occlusion in a single institution and US national database.

OBJECTIVE: This study examines associations between lipoprotein(a) (Lp[a]), a low-density-like lipoprotein, and renal vein occlusion (RVO) in US cohorts to characterize its prognostic role in the setting of RVO. DESIGN: A two-phase retrospective cohort study. METHODS: In the first phase, patients with RVO and a Lp(a) quantitative laboratory value at a single tertiary centre were reviewed. Lp(a) status was assessed in association with age of RVO diagnosis, visual acuity, time to development of RVO, and central subfield thickness. In the second phase, the TriNetX US Collaborative Network, a large national database, also was queried for the presence of high or low Lp(a) values and diagnoses of RVO. RESULTS: The single tertiary care centre identified 45 patients with RVO and a laboratory value of Lp(a), finding no significant associations with respect to Lp(a) status and age of RVO onset, time from the laboratory draw to the development of RVO, visual acuity, and central subfield thickness (p > 0.05 for all). The TriNetX national database identified 35,687 patients with a high Lp(a) value (>30 mg/dL or 61 nmol/L) and 51,692 with a low Lp(a) value. An elevated Lp(a) value was not associated with higher odds of central (odds ratio [OR] = 1.15; 95% CI, 0.88-1.50) or branch RVO (OR = 1.01; 95% CI, 0.76-1.36). CONCLUSION: Taken together, this analysis suggests a lack of association between Lp(a) value and risk of RVO. This study highlights the benefit of large national databases in the validation of laboratory value predictors identified through small-cohort observational studies.

Rapid analysis of amphetamine-type substances using Agilent's QuickProbe gas chromatograph/mass spectrometer technology.

The Agilent QuickProbe gas chromatograph/mass spectrometer (QP-GCMS) is a rapid analytical instrument requiring minimal sample preparation. The instrument was considered for the screening of samples for potential implementation at New Zealand's border screening laboratory. One of the project's primary aims was to validate the method for the analysis of border seizures, including drug concealments, novel psychoactive substances (NPS), low-dose drugs and unknown substances. For the application to be useful beyond the capabilities of current handheld point-of-contact (POC) devices, the initial evaluation has included the analysis of a large variety of compounds in a large variety of matrices. These data will be reported separately. However, during the evaluation, several chromatographical challenges were encountered during the analysis of amphetamine-type substances (ATS). As such, the QP-GCMS required some troubleshooting and method development to improve resolution for this class of compounds.

Occurrence and persistence of antibiotics administered to cattle in a newly established feedlot.

The practice of using therapeutic and prophylactic veterinary antibiotics in livestock farming is a worldwide phenomenon. Over the last decade, there has been a growing concern of antibiotic residues entering the environment via animal manure. Similar studies have focused on the occurrence and biological effects of antibiotics in land-applied animal feedlots; however, limited research has been conducted on the occurrence and persistence of antibiotics in animal feedlots. Therefore, the objective of this study was to evaluate antibiotic persistence, fate, and transport in surface water runoff and feedlot sediment in feedlot pens with livestock either receiving or not receiving antibiotic treatments through injection and feed. The two antibiotics (tylosin and monensin) added to animal feed were observed to persist in the soil environment for more than 30 days along with injected florfenicol. Monensin (5.6× higher) and tylosin (20× higher) were significantly higher in livestock pens receiving antibiotics compared to livestock pens not receiving the antibiotics. Further, rainfall was observed to significantly impact soil surface concentrations of florfenicol. Other antibiotics administrated by injection were not observed to statistically increase in concentrations in runoff or feedlot sediment. Our findings emphasize antibiotics administered in feedlots have the potential to persist and remain in feedlot sediment and runoff, particularly in instances of regular administration in feed.

Does hyperthermic povidone-iodine lavage increase the apoptotic rate of residual cancer cell in patients with malignant pleural mesothelioma?-a prospective pilot study.

Background: Malignant pleural mesothelioma (MPM) is an incurable, late presenting primary cancer, conferring a survival of 8-14 months. Different intrapleural treatments have been tested as part of a multimodality approach to treat a select group of patients with limited disease, increasing survival. Recently, povidone-iodine has been shown to induce apoptosis in microscopic tumour cells in vitro, with no reported complications. This is the first in vivo study assessing the apoptotic rate caused by intraoperative hyperthermic betadine lavage using routine immunohistochemistry combined with transmission electron microscopy (TEM). Methods: We included surgically fit patients aged >18, undergoing minimally invasive video-assisted thoracoscopic surgery (VATS) pleural biopsy between December 2016 and February 2018, for confirmed or presumed pleural malignancy. Parietal pleural biopsies were obtained at 7.5, 15 and 30 minutes after hyperthermic betadine lavage, and compared to pre-lavage biopsy samples, for apoptotic changes. Viable tumour samples underwent histological, immunohistochemical and ultrastructural analysis as well as TEM for features of apoptosis. Results: N=6. Median age was 76 years. Median overall survival was 26.7 months. There was no statistical impact on survival of side of disease (left vs. right). There was no significant difference in expressions of markers of apoptotic index pre and post betadine treatment upon immunohistochemical analysis. There was no discernible effect on morphological features of apoptosis seen with betadine treatment, on TEM analysis. No side effects were identified post betadine lavage. Conclusions: Although hyperthermic betadine lavage is a safe antiseptic solution with no toxicity when performed intraoperatively, it confers no effect on apoptotic rate or necrosis. It is therefore unlikely that hyperthermic betadine lavage will have an impact on reducing the microscopic residual disease after pleurectomy decortication and enhancing survival.

The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake.

To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen Plasmodium falciparum employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation. We further show that intravacuolar accumulation of antimalarial chemotherapeutics is surprisingly resilient to severe deacidification of the vacuole and that modulation of V-ATPase activity does not affect parasite sensitivity toward these drugs.

Wildfires correlate with reductions in aboveground tree carbon stocks and sequestration capacity on forest land in the Western United States.

In the United States (US), forest ecosystems are the largest terrestrial carbon sink, offsetting the equivalent of >12 % of economy-wide greenhouse gas (GHG) emissions annually. In the Western US, wildfires have shaped much of the landscape by changing forest structure and composition, increasing tree mortality, impacting forest regeneration, and influencing forest carbon storage and sequestration capacity. Here, we used remeasurements of >25,000 plots from the US Department of Agriculture, Forest Service Forest Inventory and Analysis (FIA) program and auxiliary information (e.g., Monitoring Trends in Burn Severity) to characterize the role of fire along with other natural and anthropogenic drivers on estimates of carbon stocks, stock changes, and sequestration capacity on forest land in the Western US. Several biotic (e.g., tree size, species, and forest structure) and abiotic factors (e.g., warm climate, severe drought, compound disturbances, and anthropogenic interventions) influenced post-fire tree mortality and regeneration and had concomitant impacts on carbon stocks and sequestration capacity. Forest ecosystems in a high severity and low frequency wildfire regime had greater reductions in aboveground biomass carbon stocks and sequestration capacity compared to forests in a low severity and high frequency fire regime. Results from this study can improve our understanding of the role of wildfire along with other biotic and abiotic drivers on carbon dynamics in forest ecosystems in the Western US.

Effectiveness of telerehabilitation and home-based falls prevention programs for community-dwelling older adults: a systematic review and meta-analysis protocol.

INTRODUCTION: Falls among older adults are associated with adverse sequelae including fractures, chronic pain and disability, which can lead to loss of independence and increased risks of nursing home admissions. The COVID-19 pandemic has significantly increased the uptake of telehealth, but the effectiveness of virtual, home-based fall prevention programmes is not clearly known. We aim to synthesise the trials on telerehabilitation and home-based falls prevention programmes to determine their effectiveness in reducing falls and adverse outcomes, as well as to describe the safety risks associated with telerehabilitation. METHODS AND ANALYSIS: This protocol was developed using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Database searches from inception to August 2022 will be conducted without language restrictions of MEDLINE, EMBASE, Ovid HealthSTAR, CINAHL, SPORTDiscus, Physiotherapy EvidenceDatabase (PEDro) and the Cochrane Library. Grey literature including major geriatrics conference proceedings will be reviewed. Using Covidence software, two independent reviewers will in duplicate determine the eligibility of randomised controlled trials (RCTs). Eligible RCTs will compare telerehabilitation and home-based fall prevention programmes to usual care among community-dwelling older adults and will report at least one efficacy outcome: falls, fractures, hospitalisations, mortality or quality of life; or at least one safety outcome: pain, myalgias, dyspnoea, syncope or fatigue. Secondary outcomes include functional performance in activities of daily living, balance and endurance. Risk of bias will be assessed using the Cochrane Collaboration tool. DerSimonian-Laird random effects models will be used for the meta-analysis. Heterogeneity will be assessed using the I2 statistic and Cochran's Q statistic. We will assess publication bias using the Egger's test. Prespecified subgroup analyses and univariate meta-regression will be used. ETHICS AND DISSEMINATION: Ethics approval is not required. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022356759.