Evaluating the Effectiveness of Lacrimal Gland Botulinum Toxin Using the TEARS Score.

PURPOSE: Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. METHODS: Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. RESULTS: Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). CONCLUSIONS: This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.

Determination of Lactose in Lactose-Free and Low-Lactose Milk, Milk Products, and Products Containing Dairy Ingredients by the LactoSens®R Amperometry Method: Final Action 2020.01.

BACKGROUND: The LactoSens®R method was previously shown to have acceptable accuracy and repeatability precision as required by AOAC Standard Method Performance Requirements (SMPR®) 2018.009 for determination of lactose in low-lactose or lactose-free milk, milk products, and products containing dairy ingredients and was awarded Official Method of AnalysisSM (OMA) First Action status in 2020. OBJECTIVE: The method was subjected to a multilaboratory validation (MLV) study to evaluate the reproducibility precision of the method. METHODS: Fourteen validation materials were provided to 15 laboratories in seven countries as blind duplicates. The materials ranged from 0 to 173 mg/100 g lactose. Each laboratory analyzed the blind duplicates according to OMA 2020.01. The data were analyzed for repeatability and reproducibility precision. RESULTS: RSDr values varied from 2.81 to 8.76%, and RSDR values varied from 4.25 to 12.5%. When sorted by category and concentration range, these results met the repeatability and reproducibility criteria required by SMPR 2018.009. CONCLUSIONS: The data generated in the MLV support the adoption of OMA 2020.01 as Final Action status. HIGHLIGHTS: The LactoSensR method, as described by OMA 2020.01, provides an accurate and precise determination of lactose in a variety of low-lactose and lactose-free milk, milk products, and products containing dairy ingredients in minutes.

Interface engineering of cellobiose dehydrogenase improves interdomain electron transfer.

Cellobiose dehydrogenase (CDH) is a bioelectrocatalyst that enables direct electron transfer (DET) in biosensors and biofuel cells. The application of this bidomain hemoflavoenzyme for physiological glucose measurements is limited by its acidic pH optimum and slow interdomain electron transfer (IET) at pH 7.5. The reason for this rate-limiting electron transfer step is electrostatic repulsion at the interface between the catalytic dehydrogenase domain and the electron mediating cytochrome domain (CYT). We applied rational interface engineering to accelerate the IET for the pH prevailing in blood or interstitial fluid. Phylogenetic and structural analyses guided the design of 17 variants in which acidic amino acids were mutated at the CYT domain. Five mutations (G71K, D160K, Q174K, D177K, M180K) increased the pH optimum and IET rate. Structure-based analysis of the variants suggested two mechanisms explaining the improvements: electrostatic steering and stabilization of the closed state by hydrogen bonding. Combining the mutations into six combinatorial variants with up to five mutations shifted the pH optimum from 4.5 to 7.0 and increased the IET at pH 7.5 over 12-fold from 0.1 to 1.24 s-1 . While the mutants sustained a high enzymatic activity and even surpassed the IET of the wild-type enzyme, the accumulated positive charges on the CYT domain decreased DET, highlighting the importance of CYT for IET and DET. This study shows that interface engineering is an effective strategy to shift the pH optimum and improve the IET of CDH, but future work needs to maintain the DET of the CYT domain for bioelectronic applications.

Effects of fenbendazole on fecal microbiome in BPH/5 mice, a model of hypertension and obesity, a brief report.

Fenbendazole (FBZ) is a common antiparasitic treatment used in research rodent colonies for biosecurity purposes. The effect of this compound has been studied in C57 mice, but never before in a strain of mice that has co-morbidities, such as the blood pressure high (BPH)/5. The BPH/5 mouse is an inbred genetic model of hypertension. While both male and female BPH/5 have high blood pressure, there is a metabolic sexual dimorphism with females displaying key features of obesity. The obese gut microbiome has been linked to hypertension. Therefore, we hypothesized that fenbendazole treatment will alter the gut microbiome in hypertensive mice in a sex dependent manner. To test the influence of FBZ on the BPH/5 gut microbiota, fecal samples were collected pre- and post-treatment from adult BPH/5 mice (males and non-pregnant females). The mice were treated with fenbendazole impregnated feed for five weeks. Post-treatment feces were collected at the end of the treatment period and DNA was extracted, and the V4 region of 16S rRNA was amplified and sequenced using the Illumina MiSeq system. The purpose was to analyze the fecal microbiome before and after FBZ treatment, the results demonstrate changes with treatment in a sex dependent manner. More specifically, differences in community composition were detected in BPH/5 non-pregnant female and males using Bray-Curtis dissimilarity as a measure of beta-diversity (treatment p = 0.002). The ratio of Firmicutes to Bacteroidetes, which has been identified in cases of obesity, was not altered. Yet, Verrucomicrobia was increased in BPH/5 males and females post-treatment and was significantly different by sex (treatment p = 5.85e-05, sex p = 0.0151, and interaction p = 0.045), while Actinobacteria was decreased in the post-treatment mice (treatment p = 0.00017, sex p = 0.5, interaction p = 0.2). These results are indicative of gut dysbiosis compared to pre-treatment controls. Lactobacillus was decreased with FBZ treatment in BPH/5 females only. In conclusion, fenbendazole does alter the gut microbial communities, most notable in the male rather than female BPH/5 mouse. This provides evidence that caution should be taken when providing any gut altering treatments before or during mouse experiments.

Metagenetic Analysis of the Pregnant Microbiome in Horses.

Placentitis is the leading cause of infectious abortion in the horse. Additionally, it can result in weak and/or growth restricted offspring. While the etiology of ascending placentitis is well described in mares, less is known regarding the pathogenesis of other types, such as nocardioform placentitis. This study aims to identify the microbial communities in different body sites of the pregnant mare in early gestation to establish a core microbiome that may be perturbed in pathologic pregnancies such as placentitis. We hypothesize that the equine placenta harbors a distinct resident microbiome in early pregnancy when characterized by metagenetics and that there will be a disparity in bacterial communities from the oral, vaginal, and fecal microbiome. Samples were collected from the oral cavity, vagina, anus, and the allantoic portion of the allantochorion ("placenta") from five pregnant mares between 96 and 120 days of gestation. The V4 region of the 16S rRNA gene was amplified for Illumina MiSeq sequencing to examine core bacterial communities present in the different body sites. Microbial community composition of the pregnant ponies by body site was significantly different (Bray-Curtis dissimilarity). The placenta was significantly different from the feces, oral cavity, and vagina. Alpha diversity measuring the Shannon diversity matrix was significant, with the body sites being a compounding variable, meaning there was a difference in richness and evenness in the different microbial communities. Feces had the greatest alpha diversity, while the oral cavity and placenta similarly had the least. In conclusion, metagenetics did reveal distinct community differences in the oral, fecal, vaginal, and placenta cavities of the horse. The equine placenta does show similarities in its microbial communities to the oral cavity. Further research needs to be completed to investigate how bacteria may be translocated to the placenta from these other body sites and how they contribute to the development of placentitis.

Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes.

Microneedle lactate sensors may be used to continuously measure lactate concentration in the interstitial fluid in a minimally invasive and pain-free manner. First- and second-generation enzymatic sensors produce a redox-active product that is electrochemically sensed at the electrode surface. Direct electron transfer enzymes produce electrons directly as the product of enzymatic action; in this study, a direct electron transfer enzyme specific to lactate has been immobilized onto a microneedle surface to create lactate-sensing devices that function at low applied voltages (0.2 V). These devices have been validated in a small study of human volunteers; lactate concentrations were raised and lowered through physical exercise and subsequent rest. Lactazyme microneedle devices show good agreement with concurrently obtained and analyzed serum lactate levels.

Automated extraction of clinical measures from videos of oculofacial disorders using machine learning: feasibility, validity and reliability.

OBJECTIVES: To determine the feasibility, validity and reliability of automatically extracting clinically meaningful eyelid measurements from consumer-grade videos of individuals with oculofacial disorders. METHODS: A custom computer program was designed to automatically extract clinical measures from consumer-grade videos. This program was applied to publicly available videos of individuals with oculofacial disorders, and age-matched controls. The primary outcomes were margin reflex distance 1 (MRD1) and 2 (MRD2), blink lagophthalmos, and ocular surface area exposure. Test-retest reliability was evaluated using Bland-Altman analysis to compare the agreement in obtained measures between separate videos of the same individual taken within 48 h of each other. RESULTS: MRD1 was reduced in individuals with ptosis versus controls (2.2 mm versus 3.4 mm, p < 0.001), and increased in individuals with facial nerve palsy (FNP) (3.9 mm, p = 0.049) and thyroid eye disease (TED) (4.1 mm; p = 0.038). Blink lagophthalmos was increased in individuals with FNP (3.7 mm); p < 0.001) and those with TED (0.1 mm, p = 0.003) versus controls (0.0 mm). Ocular surface exposure was reduced in individuals with ptosis compared with controls (12.2 mm2 versus 13.1 mm2; p < 0.001) and increased in TED (13.7 mm2; p 0.002). Bland-Altmann analysis demonstrated 95% limits of agreement for video-derived measures: median MRD1: -1.1 to 1.1 mm; median MRD2: -0.9 to 1.0 mm; blink lagophthalmos: -3.5 to 3.7 mm; and average ocular surface area exposure: -1.6 to 1.6 mm2. CONCLUSIONS: The presented program is capable of taking consumer grade videos of patients with oculofacial disease and providing clinically meaningful and reliable eyelid measurements that show promising validity.

Novel use of an autologous scleral button graft to close the anterior defect in evisceration surgery.

PURPOSE: To present an alternative evisceration technique with long-term follow-up data. This technique involves the insertion of an acrylic implant into a modified scleral shell which is closed using an autologous scleral graft. METHODS: This was a retrospective analysis of eviscerations performed in a district-general hospital in the UK. All patients underwent conventional ocular evisceration after total keratectomy. A full thickness scleral graft is harvested from the posterior sclera, using an internal approach, with an 8 mm dermatological punch. An 18-20 mm acrylic implant is placed into the shell, and the scleral graft is used to close the anterior defect. Demographic characteristics, implant size and type, and cosmetic results from pictures of all patients were recorded. All patients were invited for a review to measure motility, eyelid height, patient recorded satisfaction and complications. RESULTS: Of the five patients identified, one had since died. The remaining four attended a review in person. The mean time between surgery and review was 48 months. The mean implant size was 19 mm. There were no cases of implant extrusion or infection. All four had a <1 mm asymmetry in measured eyelid height and ≥5 mm horizontal gaze motility. All patients self-reported "good" cosmesis. An independent assessment identified "mild asymmetry" in two cases and "moderate" in the other two. CONCLUSION: Evisceration with this novel autologous scleral graft technique restores volume in the anterior orbit with good cosmetic results, and with no cases of implant exposure reported in this small case series. This technique should be compared prospectively to established techniques.

8-0 polyglactin 910 suture in entropion repair: long term follow up and rates of recurrence.

OBJECTIVES: The choice of suture is an important consideration in entropion repair, with implications on wound strength, inflammation and scar formation. There is no consensus on the best suture material or gauge of suture at present. We aim to assess the long-term outcome of entropion repair using 8-0 polyglactin sutures, with specific focus on rates of recurrence, wound dehiscence, infection and scarring. METHODS: This retrospective case series included consecutive patients from two institutions (84 eyes) undergoing entropion repair using a subciliary incision and a lateral wedge resection. Patients were invited for follow up review and patient records were evaluated to assess for cosmetic and functional outcome, complications and patient satisfaction. RESULTS: The median follow-up time from surgery was 48 months (range 20-100). There were five cases of entropion recurrence (5.9%), taking place between 8 months to 4 years after surgery, two cases required further surgery, while three were conservatively treated. There was no wound dehiscence. Two cases (2.4%) of mild superficial wound infections occurred which were successfully treated with topical antibiotics, 1 case (1.2%) of mild lid notching, and 1 case (1.2%) of scarring were recorded. 97% of patients reported to be satisfied with the outcome of their surgery. CONCLUSIONS: The use of 8-0 polyglactin suture in entropion repair has resulted in good aesthetic and functional outcome in this case series, with low rates of recurrence, complications, and no case of wound dehiscence, suggesting this suture provides sufficient tensile strength to enable wound closure and healing.

Sex-specific effects of maternal weight loss on offspring cardiometabolic outcomes in the obese preeclamptic-like mouse model, BPH/5.

AbstractPreeclampsia (PE) is a hypertensive disorder that impacts 2-8% of pregnant women worldwide. It is characterized by new onset hypertension during the second half of gestation and is a leading cause of maternal and fetal morbidity/mortality. Maternal obesity increases the risk of PE and is a key predictor of childhood obesity and potentially offspring cardiometabolic complications in a sex-dependent manner. The influence of the maternal obesogenic environment, with superimposed PE, on offspring development into adulthood is unknown. Obese BPH/5 mice spontaneously exhibit late-gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain. BPH/5 females have improved pregnancy outcomes when maternal weight loss via pair-feeding is imposed beginning at conception. We hypothesized that phenotypic differences between female and male BPH/5 offspring can be influenced by pair feeding BPH/5 dams during pregnancy. BPH/5 pair-fed dams have improved litter sizes and increased fetal body weights. BPH/5 offspring born to ad libitum dams have similar sex ratios, body weights, and fecal microbiome as well as increased blood pressure that is reduced in the dam pair-fed offspring. Both BPH/5 male and female offspring born to pair-fed dams have a reduction in adiposity and an altered gut microbiome, while only female offspring born to pair-fed dams have decreased circulating leptin and white adipose tissue inflammatory cytokines. These sexually dimorphic results suggest that reduction in the maternal obesogenic environment in early pregnancy may play a greater role in female BPH/5 sex-dependent cardiometabolic outcomes than males. Reprograming females may mitigate the transgenerational progression of cardiometabolic disease.

The 'tears' score: A tool for grading and monitoring epiphora.

PURPOSE: To test the reliability, validity and utility of the TEARS score, a scale of clinical and patient-reported severity in patients with epiphora, comprising 4 subscales: Times wiping (T), clinical Effects (E), Activity limitation (A), and symptoms of Reflex epiphora (R). METHODS: The TEARS score was completed by 136 patients with epiphora (78 treated surgically, and 51 non-surgically). Inter-rater reliability was evaluated using Cohen's Kappa and Bland-Altman analysis. 129 (95%) participants were followed up 2-6 months after baseline (non-surgical patients) or 3-6 months post-operatively (surgical patients). For each TEARS subscale, differences in scores were compared. Convergent validity was evaluated by testing correlation between TEARS and both The Lacrimal Symptom Questionnaire (Lac-Q) and The Watery Eye Quality of Life Score (WEQOL). RESULTS: Inter-rater reliability (Cohen's K) ranged from 0.5 for 'A' and 'R' to 0.8 for 'T' and 'E' subscales. Scores were lower post-operatively in surgical patients (p < 0.001). 'R' scores (reflex tearing) were higher in non-surgical cases compared with surgical (p = 0.02) but no difference was observed in other subscales at baseline. TEARS subscale scores were positively correlated with both WEQOL (r = 0.51 to 0.73) and Lac-Q score (r = 0.55 to 0.63). CONCLUSION: The TEARS score is quickly and easily implemented in a busy clinical setting. It provides an overview of both subjective and objective clinical severity in patients with epiphora, with appropriate reliability, post-operative responsiveness and convergent validity for this purpose and in this setting. It is a valuable template to be used alongside individualised symptomology.

Lower eyelid involutional entropion following cataract surgery.

OBJECTIVES: To determine whether cataract surgery is associated with an increased risk of subsequent lower eyelid entropion and evaluate potential associated factors. METHODS: This retrospective cohort study included consecutive patients undergoing first eye cataract surgery over a 10-year period at a single institution (n = 14,574). The fellow phakic eye served as control. Patient records were evaluated up until either the time of second eye cataract surgery or any other intraocular or adnexal surgery. The primary outcome was the rate of entropion repair in both the pseudophakic (exposed) group and the phakic control group. Groups were compared using relative risk and Kaplan-Meier analysis. Multivariate logistic regression was used to compare pre-specified characteristics of those patients that underwent entropion repair in their pseudophakic eye with those that did not. RESULTS: A fourfold higher relative risk of undergoing entropion repair was observed in eyes that had undergone cataract surgery compared with the fellow unoperated eye (95% confidence interval 1.6-9.8; P < 0.001) with an increased risk at all timepoints between 1 and 12 years according to Kaplan-Meier analysis (P = 0.001). Median time to entropion repair after cataract surgery was 58 months (range 3-124). Documented intraoperative patient factors such as patient or eye movement, eyelid squeezing, pain or anxiety were an independent risk factor for subsequent entropion (P < 0.0001). CONCLUSIONS: Cataract surgery is associated with an increased risk of subsequent lower eyelid entropion. Surgeons should be aware of this risk in the pre- and post-operative assessment of patients undergoing cataract surgery.

The watery eye quality of life (WEQOL) questionnaire: a patient-reported outcome measure for surgically amenable epiphora.

OBJECTIVE OR PURPOSE: To develop and test a patient-reported outcome measure for assessing health-related quality of life (HRQOL) in surgically amenable epiphora. DESIGN: Questionnaire development and validation study. PARTICIPANTS: 201 patients with a cause of epiphora amenable to surgical intervention, recruited across three independent centres. METHODS, INTERVENTION OR TESTING: The watery eye quality of life (WEQOL) questionnaire was developed and refined according to defined psychometric standards. Both surgical and non-surgical participants completed WEQOL at baseline and follow-up (>3 months), along with the Lacrimal Symptom Questionnaire (Lac-Q), RAND Short Form Health Survey (SF-36) and Glasgow Benefit Inventory (GBI). Convergent validity of WEQOL was evaluated according to correlation (R > 0.40) with each of these additional tests. Responsiveness of WEQOL to intervention was evaluated according to patient-reported success. Test-retest reliability was assessed by the Bland-Altman method and intraclass correlation (ICC) in a subset of 64 participants at baseline. MAIN OUTCOME MEASURES: WEQOL construct validity, responsiveness and test-retest reliability. RESULTS: WEQOL was moderately correlated (R > 0.4) with the Lac-Q and several subscales of the SF-36 (physical role limitation, social, emotional role limitation and emotional well-being). A stronger correlation was found between the change in WEQOL at follow-up and GBI (R = 0.61). An appropriate graded response was found with a significant change in WEQOL score being observed in patients reporting successful (-28%, p < 0.0001) and partially successful surgery (-6%, p = 0.04), but not in those reporting unsuccessful surgery (+2%, p = 0.9). High test-retest reliability was observed (ICC = 0.93). CONCLUSIONS: The WEQOL questionnaire has been developed systematically according to modern psychometric standards and has been designed to evaluate the quality of life in patients with epiphora that is of a surgically amenable cause. In this study, it has demonstrated appropriate test-retest reliability, responsiveness and construct validity.

Engineering the Turnover Stability of Cellobiose Dehydrogenase toward Long-Term Bioelectronic Applications.

Cellobiose dehydrogenase (CDH) is an attractive oxidoreductase for bioelectrochemical applications. Its two-domain structure allows the flavoheme enzyme to establish direct electron transfer to biosensor and biofuel cell electrodes. Yet, the application of CDH in these devices is impeded by its limited stability under turnover conditions. In this work, we aimed to improve the turnover stability of CDH by semirational, high-throughput enzyme engineering. We screened 13 736 colonies in a 96-well plate setup for improved turnover stability and selected 11 improved variants. Measures were taken to increase the reproducibility and robustness of the screening setup, and the statistical evaluation demonstrates the validity of the procedure. The selected CDH variants were expressed in shaking flasks and characterized in detail by biochemical and electrochemical methods. Two mechanisms contributing to turnover stability were found: (i) replacement of methionine side chains prone to oxidative damage and (ii) the reduction of oxygen reactivity achieved by an improved balance of the individual reaction rates in the two CDH domains. The engineered CDH variants hold promise for the application in continuous biosensors or biofuel cells, while the deduced mechanistic insights serve as a basis for future enzyme engineering approaches addressing the turnover stability of oxidoreductases in general.

Determination of Lactose in Lactose-Free and Low-Lactose Milk, Milk Products, and Products Containing Dairy Ingredients by the LactoSens®R Amperometry Method: First Action 2020.01.

BACKGROUND: The AOAC Stakeholder Panel on Strategic Food Analytical Methods approved Standard Method Performance Requirements (SMPR®) 2018.009 for lactose in low-lactose or lactose-free milk, milk products, and products containing dairy ingredients. The LactoSens®R Method is a biosensor assay kit developed for the determination of lactose in a variety of lactose-free or low-lactose milk, dairy, and infant formula products produced with yeast-neutral lactases. OBJECTIVE: In response to a call for methods, the LactoSensR method was validated in a single laboratory study with comparison to SMPR 2018.009. METHOD: The LactoSensR method was evaluated for calibration, interference, repeatability, recovery, and robustness. In a method comparison study samples naturally containing low levels of lactose were evaluated using LactoSensR and an accredited high-performance anion-exchange chromatography with pulsed amperometric detection. RESULTS: Calibration with lactose standard solutions was shown to be linear and the method was shown to be free of interference from a variety of sugars, vitamins, alcohols, flavorings, and other compounds. Matrix studies, including 85 spiked materials, 55 products naturally containing lactose, and 13 reference materials, resulted in RSDr of 0-10.5% at 8-100 mg lactose/100 g and 0.2-5.4% at >100 mg lactose/100 g for milk and dairy products and 1.0-6.8% for infant formula, in compliance with SMPR 2018.009 with few exceptions. Recovery was 85.0-110.3% at 8-100 mg lactose/100 g and 85.6-109.7% at >100 mg lactose/100 g for milk and dairy products and 91.1-97.0% for infant formula, also meeting the performance requirements with few exceptions. The method was shown to be robust to changes in ambient temperature, sample temperature, and sample volume. CONCLUSIONS: The LactoSensR method compares favorably with the requirements of SMPR 2018.009 and should be adopted as a First Action AOAC Official MethodSM. HIGHLIGHTS: The LactoSensR method is a fast, easy-to-use method that meets the requirements of SMPR 2018.009.

Physical, ecological and human dimensions of environmental change in Brazil's Pantanal wetland: Synthesis and research agenda.

The Pantanal is the world's largest freshwater wetland, located in the geographical centre of South America. It is relatively well conserved, and features unique landscapes, ecosystems, and traditional cultural practices, shaped by the dynamic interaction of climatological, hydrological, geological, ecological, and anthropogenic factors. Its ecological integrity is increasingly threatened by human activities, particularly, in the wider catchment area, for example, deforestation, agricultural intensification, and construction of hydropower plants, with implications for local people's livelihoods. We present a synthesis of current literature on physical, ecological, and human dimensions of environmental change in the wetland, outline key research gaps, and discuss environmental management implications. The literature review suggests that better integration of insights from multiple disciplines is needed and that environmental management could be improved through a better grounding in traditional practices and local perspectives. We conclude with four recommendations: First, future environmental change research should build more strongly on the positive example of a small number of case studies where traditional and local knowledge of the environment was put into a dialogue with scientific knowledge and techniques. Second, we recommend a more explicit consideration of longer temporal scales (>10 years) in environmental change research, making use of oral and written histories, as well as palaeoecological techniques, to understand system responses to different magnitudes of human and climatic pressures, and ultimately, to inform future adaptation activities. Third, we suggest that enhanced stakeholder participation in conceiving and implementing research projects in the Pantanal would strengthen the practical relevance of research in addressing environmental management challenges, livelihood needs, and advocacy processes. Fourth, we call for a more systemic and integrative perspective on environmental education, which encompasses engagement activities between researchers, policy-makers, and citizens, to foster environmental awareness, scientific literacy, and public participation.

A Systematic Review of Patient-Reported Outcomes for Surgically Amenable Epiphora.

PURPOSE: In evaluating epiphora and its management, the bottom line for all stakeholders is whether an intervention confers any real benefit on quality of life. A review was conducted to identify and appraise patient-reported outcome measures (PROMs) in surgically amenable epiphora. METHODS: A systematic search was conducted of studies relating to surgical intervention for epiphora. Patient-reported outcome measures were identified and assessed against standard criteria. RESULTS: Of 30,544 identified articles, 227 were eligible for data extraction. Of these, 69% reported a PROM as the primary outcome. PROMs identified included single-item symptom scores (48% of primary outcome PROMs), single-item reports of improvement (30%), the Glasgow Benefit Inventory (3%), Lacrimal Symptom Questionnaire (0.5%), Nasolacrimal Duct Obstruction Symptom Score (0.5%), Ocular Surface Disease Index (0.5%), Visual Function Questionnaire-25, the Short Form-36 Health Survey, and 3 other symptom scores. None were developed through consultation with the target population, and there was inadequate testing of content validity. The strengths and limitations of each PROM are presented, with regard to interpretation, responsiveness, reliability, and validity. DISCUSSION: The importance of robust and psychometrically sound PROMs is essential if the under-reporting of quality of life improvement in patients treated for epiphora is to change. Recommendations for the use of each identified PROM are discussed. CONCLUSIONS: Several PROMs have been used in the recent literature to evaluate patients undergoing surgery to treat epiphora. Assessed against standard criteria, no PROM has proven to be both psychometrically robust and clinically meaningful for use in this population. Future PROM development should be guided by this standard framework.

An evaluation of intracameral mydriasis for routine cataract surgery.

BACKGROUND: Intracameral Mydrane might facilitate a more streamlined cataract service and improve the patient experience. There is limited 'real-world' evidence of its use in a UK setting. METHODS: As part of a local evaluation of cataract surgery using intracameral Mydrane (group 2; n=60), data were collected on intraoperative pupil size and postoperative visual acuity (VA), as well as the rate of mechanical pupil dilation, intraoperative floppy iris syndrome (IFIS) and complications. Preoperative and theatre turnaround time was recorded and patients completed a validated measure of satisfaction postoperatively. Data were compared with a previous cohort subjected to the existing standard regime of preoperative topical mydriatics (group 1; n=60). RESULTS: Postoperative VA was comparable between groups (0.09±0.16 vs 0.08±0.15; p=0.59). Pupil size in group 2 was 7.0±1.0 mm prior to capsulorhexis and 6.5±0.29 mm after cortical aspiration, with a smaller pupil in patients on alpha-antagonists (4.7±1.1 mm; p=0.004) at this later time point. Comparing group 2 with group 1, preoperative waiting was less (87 vs 146 min; p<0.0001) and satisfaction was higher (76.0±11.2 vs 66.3±8.6; p<0.0001), although theatre turnaround time was longer (25 min vs 22 min). CONCLUSION: Intracameral mydriasis was clinically effective in most patients undergoing cataract surgery and might be associated with an improved patient experience and a more streamlined preoperative flow. Mydrane represents a licensed alternative to the off-label use of other intracameral mydriatic agents, but was not judged to be a cost-effective intervention for routine use in this particular setting.

Rapid regrowth and detection of microbial contaminants in equine fecal microbiome samples.

Advances have been made to standardize 16S rRNA gene amplicon based studies for inter-study comparisons, yet there are many opportunities for systematic error that may render these comparisons improper and misleading. The fecal microbiome of horses has been examined previously, however, no universal horse fecal collection method and sample processing procedure has been established. This study was initialized in large part to ensure that samples collected by different individuals from different geographical areas (i.e., crowdsourced) were not contaminated due to less than optimal sampling or holding conditions. In this study, we examined the effect of sampling the surface of fecal pellets compared to homogenized fecal pellets, and also the effect of time of sampling after defecation on 'bloom' taxa (bloom taxa refers to microbial taxa that can grow rapidly in horse feces post-defecation) using v4 16S rRNA amplicon libraries. A total of 1,440,171 sequences were recovered from 65 horse fecal samples yielding a total of 3,422 OTUs at 97% similarity. Sampling from either surface or homogenized feces had no effect on diversity and little effect on microbial composition. Sampling at various time points (0, 2, 4, 6, 12 h) had a significant effect on both diversity and community composition of fecal samples. Alpha diversity (Shannon index) initially increased with time as regrowth taxa were detected in the amplicon libraries, but by 12 h the diversity sharply decreased as the community composition became dominated by a few bloom families, including Bacillaceae, Planococcaeae, and Enterococcaceae, and other families to a lesser extent. The results show that immediate sampling of horse feces must be done in order to ensure accurate representation of horse fecal samples. Also, several of the bloom taxa found in this study are known to occur in human and cattle feces post defecation. The dominance of these taxa in feces shortly after defecation suggests that the feces is an important habitat for these organisms, and horse fecal samples that were improperly stored can be identified by presence of bloom taxa.