Comparative efficacy of low-volume retrobulbar anesthesia using three commercial local anesthetics in adult horses.

OBJECTIVE: To compare the efficacy of low-volume (5-mL) locoregional retrobulbar anesthesia ("retrobulbar block") by use of 3 commercial local anesthetic formulations. ANIMALS: 8 healthy adult mares. METHODS: A block-randomized, masked, controlled design was used. A single ultrasound-guided retrobulbar block was performed with 2% lidocaine, 2% mepivacaine, or 0.5% bupivacaine (n = 5 eyes/group). Contralateral eyes served as untreated controls. End points performed at baseline and time intervals up to 24 hours postblock included the following: assessment of neurophthalmic reflexes/responses, intraocular pressure, and vertical pupil diameter measurement, corneal and periocular esthesiometry, and observation for adverse effects. RESULTS: Low-volume block did not result in increased intraocular pressure or other adverse effects at any time point in any treatment group. Statistically significant corneal anesthesia (P < .001) was observed 1 minute after block in all groups, persisting through 4 hours after lidocaine or mepivacaine block and through 24 hours after bupivacaine block. Clinically significant periocular anesthesia was not observed in any group. Significant vertical pupil diameter increase (P < .05) was observed for up to 4 hours after lidocaine or mepivacaine block and 6 hours after bupivacaine block. CLINICAL RELEVANCE: Low-volume retrobulbar block with any of the 3 local anesthetic drugs evaluated was not associated with adverse effects. In terms of efficacy, mepivacaine block showed no clinical advantage over lidocaine block. However, bupivacaine block induced comparatively rapid and sustained corneal anesthesia. In comparison to published findings using a larger injection volume, low-volume retrobulbar block with lidocaine produced clinically comparable corneal anesthesia. However, periocular soft tissue anesthesia was not achieved with any local anesthetic drug at low volume.

Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

OBJECTIVES: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs). DESIGN: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. PROCEDURES: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. RESULTS: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. CONCLUSIONS: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs.

Analogs of α-conotoxin PnIC selectively inhibit α7ß2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.

This study was undertaken to identify and characterize the first ligands capable of selectively identifying nicotinic acetylcholine receptors containing α7 and ß2 subunits (α7ß2-nAChR subtype). Basal forebrain cholinergic neurons express α7ß2-nAChR. Here, they appear to mediate neuronal dysfunction induced by the elevated levels of oligomeric amyloid-ß associated with early Alzheimer's disease. Additional work indicates that α7ß2-nAChR are expressed across several further critically important cholinergic and GABAergic neuronal circuits within the central nervous system. Further studies, however, are significantly hindered by the inability of currently available ligands to distinguish heteromeric α7ß2-nAChR from the closely related and more widespread homomeric α7-only-nAChR subtype. Functional screening using two-electrode voltage-clamp electrophysiology identified a family of α7ß2-nAChR-selective analogs of α-conotoxin PnIC (α-CtxPnIC). A combined electrophysiology, functional kinetics, site-directed mutagenesis, and molecular dynamics approach was used to further characterize the α7ß2-nAChR selectivity and site of action of these α-CtxPnIC analogs. We determined that α7ß2-nAChR selectivity of α-CtxPnIC analogs arises from interactions at a site distinct from the orthosteric agonist-binding site shared between α7ß2- and α7-only-nAChR. As numerous previously identified α-Ctx ligands are competitive antagonists of orthosteric agonist-binding sites, this study profoundly expands the scope of use of α-Ctx ligands (which have already provided important nAChR research and translational breakthroughs). More immediately, analogs of α-CtxPnIC promise to enable, for the first time, both comprehensive mapping of the distribution of α7ß2-nAChR and detailed investigations of their physiological roles.

The negative impact of global health worker migration, and how it can be addressed.

International migration of healthcare workers is well established and has become a means of maintaining service quality in many high income countries. In recent years, there has been a dramatic increase in recruitment of health personnel who have been trained abroad, including from the poorest countries in the world. In this article, using General Medical Council (GMC) data, we chart the growth in numbers of international staff working in the United Kingdom, where since 2018, over half of all new GMC registrations have been of doctors trained abroad. There is evidence that this migration of health staff results in poorer health service provision in low and middle income countries, as well as substantial economic impacts in these countries that have invested in training their health workforce. Recruiting governments have argued that remittances compensate for the loss of personnel, and that training opportunities can enable skills transfer to countries with weaker health systems. However, we found that the costs to the source countries dwarfed remittances, and that only a tiny fraction of people who move to take up posts in wealthier countries ever return to their countries of origin to work. We conclude that in addition to the investment in health systems (and workforce development) in low and middle income countries as part of Official Development Assistance for Health, there is an urgent need to increase training of nurses and doctors so that damaging migration is no longer relied upon to fill gaps in healthcare personnel.

Evaluation for endotoxin in intraocular materials used during phacoemulsification surgery using a recombinant factor C assay.

OBJECTIVE: Cataract surgery remains the sole method to resolve blindness secondary to cataract formation. One complication includes fibrin web formation post-operatively. This study aimed to investigate the presence of endotoxin within materials used during cataract surgery as a possible cause of fibrin web phenomenon. METHODS: Preservative-free epinephrine, heparin, viscoelastic devices, and intraocular lenses were collected for evaluation. Various manufacturers and manufacturing lot numbers were used when available. Viscosity of viscoelastics was reduced by incubating samples with human recombinant hyaluronidase. Intraocular product (IOL) packaging fluid was collected and stored for testing. The IOLs were then washed with a sterile balanced salt solution, incubated at 37°C for 48 h, and then fluid was collected for testing to mimic intraocular placement. Samples were tested using a commercially available rFC kit. Fluorescence was measured at time zero and after 1 h using a fluorescence microplate reader. The change in fluorescence was corrected for blank fluorescence and plotted to a standard curve. RESULTS: Endotoxin levels were below the limit of detection (0.05 EU/mL) in all samples. Incubation of IOLs at intraocular temperature did not increase extraction of endotoxin. CONCLUSION: Endotoxin was not identified in any tested sample, including those used in cases of fibrin web formation post-phacoemulsification. As fibrin webs are often observed episodically, it is possible that endotoxin levels may vary between batches, or that endotoxin is not related to fibrin formation.

Reprioritising global mental health: psychoses in sub-Saharan Africa.

Arthur Kleinman's 2009 Lancet commentary described global mental health as a "moral failure of humanity", asserting that priorities should be based not on the epidemiological and utilitarian economic arguments that tend to favour common mental health conditions like mild to moderate depression and anxiety, but rather on the human rights of those in the most vulnerable situations and the suffering that they experience. Yet more than a decade later, people with severe mental health conditions like psychoses are still being left behind. Here, we add to Kleinman's appeal a critical review of the literature on psychoses in sub-Saharan Africa, highlighting contradictions between local evidence and global narratives surrounding the burden of disease, the outcomes of schizophrenia, and the economic costs of mental health conditions. We identify numerous instances where the lack of regionally representative data and other methodological shortcomings undermine the conclusions of international research carried out to inform decision-making. Our findings point to the need not only for more research on psychoses in sub-Saharan Africa, but also for more representation and leadership in the conduct of research and in international priority-setting more broadly-especially by people with lived experience from diverse backgrounds. This paper aims to encourage debate about how this chronically under-resourced field, as part of wider conversations in global mental health, can be reprioritised.

High-throughput cell-based assays for identifying antagonists of multiple smoking-associated human nicotinic acetylcholine receptor subtypes.

There is substantial evidence that in addition to nicotine, other compounds found in tobacco smoke significantly influence smoking behavior. Further, recent years have seen an explosion in the availability of non-combusted products that deliver nicotine, such as e-cigarettes and "home-brew" vaping devices that are essentially unregulated. There are many thousands of compounds in tobacco smoke alone, and new products are constantly introducing new compounds. Uncovering which of these compounds are active, across multiple smoking-relevant subtypes of the nicotinic acetylcholine receptor (nAChR) that influence tobacco/nicotine addiction, requires a high-throughput screening (HTS) approach. Accordingly, we developed a panel of HTS-friendly cell-based assays, all performed in the same cellular background and using the same membrane potential dye readout, to measure the function of the α3ß4-, α4ß2-, and α6ß2-nAChR subtypes. These subtypes have each been prominently and consistently associated with human smoking behavior. We validated our assays by performing pilot screening of an expanded set of the Prestwick FDA-approved drug library. The screens displayed excellent performance parameters, and moderate hit rates (mean of 1.2% across all three assays) were achieved when identifying antagonists (chosen since effects of endogenous antagonists on consumption of nicotine/tobacco products are under-studied). Validation rates using an orthogonal assay (86Rb+ efflux) averaged 73% across the three assays. The resulting panel of assays represents a valuable new platform with which to screen and identify nAChR subtype-selective compounds. This provides a resource for identifying smoking-related compounds in both combusted and non-combusted tobacco products, with potential relevance in the search for additional smoking-cessation therapies.

Lessons from a theory of change-driven evaluation of a global mental health funding portfolio.

BACKGROUND: Given the underinvestment in global mental health to-date, it is important to consider how best to maximize the impact of existing investments. Theory of Change (ToC) is increasingly attracting the interest of funders seeking to evaluate their own impact. This is one of four papers investigating Grand Challenges Canada's (GCC's) first global mental health research funding portfolio (2012-2016) using a ToC-driven approach. METHODS: A portfolio-level ToC map was developed through a collaborative process involving GCC grantees and other key stakeholders. Proposed ToC indicators were harmonised with GCC's pre-existing Results-based Management and Accountability Framework to produce a "Core Metrics Framework" of 23 indicators linked to 17 outcomes of the ToC map. For each indicator relevant to their project, the grantee was asked to set a target prior to the start of implementation, then report results at six-month intervals. We used the latest available dataset from all 56 projects in GCC's global mental health funding portfolio to produce a descriptive analysis of projects' characteristics and outcomes related to delivery. RESULTS: 12,999 people were trained to provide services, the majority of whom were lay or other non-specialist health workers. Most projects exceeded their training targets for capacity-building, except for those training lay health workers. Of the 321,933 people screened by GCC-funded projects, 162,915 received treatment. Most projects focused on more than one disorder and exceeded all their targets for screening, diagnosis and treatment. Fewer people than intended were screened for common mental disorders and epilepsy (60% and 54%, respectively), but many more were diagnosed and treated than originally proposed (148% and 174%, respectively). In contrast, the three projects that focused on perinatal depression exceeded screening and diagnosis targets, but only treated 43% of their intended target. CONCLUSIONS: Under- or over-achievement of targets may reflect operational challenges such as high staff turnover, or challenges in setting appropriate targets, for example due to insufficient epidemiological evidence. Differences in delivery outcomes when disaggregated by disorder suggest that these challenges are not universal. We caution implementers, funders and evaluators from taking a one-size-fits all approach and make several recommendations for how to facilitate more in-depth, multi-method evaluation of impact using portfolio-level ToC.

Evaluation of the effect of disposable tonometer cover brand on performance of Tono-Pen Vet in canine eyes.

PRIMARY OBJECTIVE: To evaluate the effect of latex tip cover manufacturer on accuracy and repeatability of Tono-Pen Vet™ in canine eyes. ANIMAL STUDIED: Twelve enucleated globes from six dogs. PROCEDURES: The anterior chamber was cannulated and connected to a calibrated manometer. Intraocular pressure (IOP) measurements were obtained using the Tono-Pen Vet and TONOVET Plus at manometric IOP ranging from 5 to 80 mmHg. At each IOP, the Tono-Pen Vet was used with a new Ocu-Film™ latex tip cover (the only manufacturer-approved brand of cover) followed by a new Softips™ latex tip cover. For comparison, the TONOVET Plus was also used at each IOP with a new disposable rebound probe. Measured IOP values were analyzed by linear regression and intraclass correlation coefficient (ICC). RESULTS: Tono-Pen Vet accuracy was unaffected by tip cover manufacturer or by frequent change in cover. Using ICC analysis, repeatability of measurements using either tonometer was good to excellent at physiologic IOP levels but variably decreased with both devices at supraphysiologic IOP. CONCLUSIONS: Neither tip cover manufacturer nor frequent changes in tip cover adversely affect Tono-Pen Vet accuracy. Measurement repeatability with Tono-Pen Vet and TONOVET Plus is widely variable at supraphysiologic IOP. Therefore, minor changes in IOP >25 mmHg should not be used to make clinical decisions without considering this variability.

Reducing stigma and discrimination associated with COVID-19: early stage pandemic rapid review and practical recommendations.

AIMS: To develop recommendations for strategies and interventions to reduce stigma and discrimination related to coronavirus disease 2019 (COVID-19), through reviewing and synthesising evidence in relation to COVID-19 and other disease outbreaks and infectious/stigmatised conditions from systematic reviews and primary studies and recommendations from additional materials. METHODS: Rapid review, drawing on the World Health Organization's (WHO) methodology for developing interim guidelines during health emergencies. PubMed/MEDLINE, PsycINFO, Cochrane Central and Campbell Collaboration searched up to mid-April 2020. Searches were supplemented by reference-searching and expert recommendations. Searches were designed to identify: (1) systematic reviews (<10 years), or (2) primary intervention studies (no date limit) reporting evidence on anti-stigma interventions (in relation to COVID-19 or other infectious/stigmatised conditions) or (3) additional relevant materials. Data were extracted on population, intervention, outcome and results. These data were compiled into evidence summary tables and narrative overviews. Recommendations on strategies for COVID-19 stigma-reduction were developed using the WHO 'Evidence to Decision' framework approach. The review protocol was registered with PROSPERO (registration ID: CRD42020177677). RESULTS: The searches identified a total of 4150 potentially relevant records, from which 12 systematic reviews and 29 additional articles were included. Overarching considerations and specific recommendations focus on: (1) language/words used in relation to COVID-19 and affected people; (2) media/journalistic practices; (3) public health interventions; (4) targeted public health interventions for key groups and (5) involving communities and key stakeholders. CONCLUSIONS: These recommendations represent the first consolidated evidence-based guidance on stigma and discrimination reduction in relation to COVID-19. Mitigating the impact of stigma is critical in reducing distress and negative experiences, and strengthening communities' resolve to work together during exceptional circumstances. Ultimately, reducing stigma helps addressing structural inequalities that drive marginalisation and exacerbate both health risks and the impact of stigma. Administrations and decision makers are urged to consider integrating these recommendations into the ongoing COVID-19 response.

Core components of mental health stigma reduction interventions in low- and middle-income countries: a systematic review.

AIMS: To identify and categorise core components of effective stigma reduction interventions in the field of mental health in low- and middle-income countries (LMICs) and compare these components across cultural contexts and between intervention characteristics. METHODS: Seven databases were searched with a strategy including four categories of terms ('stigma', 'mental health', 'intervention' and 'low- and middle-income countries'). Additional methods included citation chaining of all papers identified for inclusion, consultation with experts and hand searching reference lists from other related reviews. Studies on interventions in LMICs aiming to reduce stigma related to mental health with a stigma-related outcome measure were included. All relevant intervention characteristics and components were extracted and a quality assessment was undertaken. A 'best fit' framework synthesis was used to organise data, followed by a narrative synthesis. RESULTS: Fifty-six studies were included in this review, of which four were ineffective and analysed separately. A framework was developed which presents a new categorisation of stigma intervention components based on the included studies. Most interventions utilised multiple methods and of the 52 effective studies educational methods were used most frequently (n = 83), and both social contact (n = 8) and therapeutic methods (n = 3) were used infrequently. Most interventions (n = 42) based their intervention on medical knowledge, but a variety of other themes were addressed. All regions with LMICs were represented, but every region was dominated by studies from one country. Components varied between regions for most categories indicating variation between cultures, but only a minority of studies were developed in the local setting or culturally adapted. CONCLUSIONS: Our study suggests effective mental health stigma reduction interventions in LMICs have increased in quantity and quality over the past five years, and a wide variety of components have been utilised successfully - from creative methods to emphasis on recovery and strength of people with mental illness. Yet there is minimal mention of social contact, despite existing strong evidence for it. There is also a lack of robust research designs, a high number of short-term interventions and follow-up, nominal use of local expertise and the research is limited to a small number of LMICs. More research is needed to address these issues. Some congruity exists in components between cultures, but generally they vary widely. The review gives an in-depth overview of mental health stigma reduction core components, providing researchers in varied resource-poor settings additional knowledge to help with planning mental health stigma reduction interventions.

Partnership for the implementation of mental health policy in Nigeria: a case study of the Comprehensive Community Mental Health Programme in Benue State.

BACKGROUND: 71% of countries in the World Health Organisation's (WHO's) African Region have a stand-alone mental health policy or plan, but only 14% have fully implemented it. In Nigeria, integration of mental health into primary care has been a stumbling block to the implementation of the 1991 National Mental Health Policy, 2013 Policy on Mental Health Services Delivery and the National Mental, Neurological and Substance Use Programme and Action Plan. A partnership between public and private not-for-profits in Benue State, the Comprehensive Community Mental Health Programme (CCMHP) has successfully integrated mental health into primary care in alignment with the national mental health policy and the WHO's mental health Gap Action Programme Intervention Guide (mhGAP-IG). There is a need to document such examples in order to inform policy implementation in Nigeria and other low- and middle-income countries (LMICs). METHODS: We followed the Case Study Methodology to Monitor and Evaluate Community Mental Health Programmes in LMICs. Four field visits were conducted between 2013 and 2017 to document the first phase of activities of CCMHP, covering the period of January 2011 through June 2016. RESULTS: In its first phase, CCMHP trained 19 community psychiatric nurses and 48 community health extension workers in mhGAP-IG, establishing 45 new mental health clinics in primary care facilities across Benue, a state more populous than many countries. As a result, 13,785 clients (55% male, 45% female) were enrolled in mental health services either in primary care or in one of two pre-existing community-based rehabilitation facilities. Most are adults over age 18 (82.75%), and present to services with epilepsy (52.38%) or psychosis (38.41%). CONCLUSION: The case of CCMHP demonstrates it is possible to rapidly scale-up mental health services in line with national mental health policy using the mhGAP-IG, even in a challenging, low-resource setting. Multi-sectoral partnerships may help to overcome some of the barriers to successful integration of mental health into general healthcare by capitalising on the resources and expertise of both state and non-state actors. However, a difficult political context could threaten the sustainability of the programme if funder requirements force a rapid transition to full government ownership.

α1-FANGs: Protein Ligands Selective for the α-Bungarotoxin Site of the α1-Nicotinic Acetylcholine Receptor.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play a central role in neuronal and neuromuscular signal transduction. Here, we have developed FANG ligands, fibronectin antibody-mimetic nicotinic acetylcholine receptor-generated ligands, using mRNA display. We generated a 1 trillion-member primary e10FnIII library to target a stabilized α1 nicotinic subunit (α211). This library yielded 270000 independent potential protein binding ligands. The lead sequence, α1-FANG1, represented 25% of all library sequences, showed the highest-affinity binding, and competed with α-bungarotoxin (α-Btx). To improve this clone, a new library based on α1-FANG1 was subjected to heat, protease, binding, off-rate selective pressures, and point mutations. This resulted in α1-FANG2 and α1-FANG3. These proteins bind α211 with KD values of 3.5 nM and 670 pM, respectively, compete with α-Btx, and show improved subunit specificity. α1-FANG3 is thermostable ( Tm = 62 °C) with a 6 kcal/mol improvement in folding free energy compared with that of the parent α1-FANG1. α1-FANG3 competes directly with the α-Btx binding site of intact neuromuscular heteropentamers [(α1)2ß1γδ] in mammalian culture-derived cellular membranes and in Xenopus laevis oocytes expressing these nAChRs. This work demonstrates that mRNA display against a monomeric ecto-domain of a pentamer has the capability to select ligands that bind that subunit in both a monomeric and a pentameric context. Overall, our work provides a route to creating a new family of stable, well-behaved proteins that specifically target this important receptor family.

Education, substance use, and HIV risk among orphaned adolescents in Eastern Zimbabwe.

There is a growing interest in education as a means to reduce HIV infection in vulnerable children in sub-Saharan Africa; however, the mechanisms by which education reduces HIV infection remain uncertain. Substance use has been associated with high-risk sexual behaviour and could lie on the causal pathway between education and HIV risk. Therefore, we used multivariable regression to measure associations between: (i) orphanhood and substance use (alcohol, recreational drugs, and smoking), (ii) substance use and sexual risk behaviours, and (iii) school enrolment and substance use, in adolescents aged 15-19 years, in Eastern Zimbabwe. We found substance use to be low overall (6.4%, 3.2%, and 0.9% of males reported alcohol, drug, and cigarette use; <1% of females reported any substance use), but was more common in male maternal and double orphans than non-orphans. Substance use was positively associated with early sexual debut, number of sexual partners, and engaging in transactional sex, while school enrolment was associated with lower substance use in males. We conclude that education may reduce sexual risk behaviours and HIV infection rates among male adolescents in sub-Saharan Africa, in part, by reducing substance abuse.

Occupational medicine specialist referral triggers: Mixed-methods analysis of teleconsult cases.

Background: Qualitative analyses can yield critical lessons for learning organizations in healthcare. Few studies have applied these techniques in the field of occupational and environmental medicine (OEM). Aims: To describe the characteristics of complex cases referred for OEM subspecialty evaluation and variation by referring provider's training. Methods: Using a mixed methods approach, we conducted a content analysis of clinical cases submitted to a national OEM teleconsult service. Consecutive cases entered between April 2014 and July 2015 were screened, coded and analysed. Results: 108 cases were available for analysis. Local Veterans Health Administration (VHA) non-specialist providers entered a primary medical diagnosis in 96% of cases at the time of intake. OEM speciality physicians coded significant medical conditions based on free text comments. Coder inter-rater reliability was 84%. The most frequent medical diagnosis types associated with tertiary OEM referral by non-specialists were endocrine (19%), cardiovascular (18%) and mental health (16%). Concern for usage of controlled and/or sedating medications was cited in 1% of cases. Compared to referring non-specialists, OEM physicians were more likely to attribute case complexity to musculoskeletal (OR: 2.3, 1.68-3.14) or neurological (OR: 1.69, 1.28-2.24) conditions. Medication usage (OR: 2.2, 1.49-2.26) was more likely to be a source of clinical concern among referring providers. Conclusions: The findings highlight the range of triggers for OEM physician subspecialty referral in clinical practice with employee patients. The results of this study can be used to inform development of provider education, standardized clinical practice pathways, and quality review activities for occupational medicine practitioners.

Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow.

The relationship between HIV and fertility in the era of antiretroviral therapy in sub-Saharan Africa: evidence from 49 Demographic and Health Surveys.

OBJECTIVES: To describe regional differences in the relative fertility of HIV-positive vs. HIV-negative women and changes as antiretroviral treatment (ART) is scaled up, to improve estimates of predicted need for and coverage of prevention of mother-to-child transmission services at national and subnational levels. METHODS: We analysed 49 nationally representative household surveys in sub-Saharan Africa between 2003 and 2016 to estimate fertility rate ratios of HIV-positive and HIV-negative women by age using exponential regression and test for regional and urban/rural differences. We estimated the association between national ART coverage and the relationship between HIV and fertility. RESULTS: Significant regional differences exist in HIV and fertility relationships, with less HIV-associated subfertility in Southern Africa. Age patterns of relative fertility are similar. HIV impact on fertility is weaker in urban than rural areas. For women below age 30, regional and urban/rural differences are largely explained by differences in age at sexual debut. Higher levels of national ART coverage were associated with slight attenuation of the relationship between HIV and fertility. CONCLUSIONS: Regional differences in HIV-associated subfertility and urban-rural differences in age patterns of relative fertility should be accounted for when predicting need for and coverage of PMTCT services at national and subnational level. Although HIV impacts on fertility are somewhat reduced at higher levels of national ART coverage, differences in fertility between HIV positive and negative remain, and fertility of women on ART should not be assumed to be the same as HIV-negative women. There were few data in recent years, when ART has reached high levels, and this relationship should continue to be assessed as further evidence becomes available.

Folding sticky elastica: dynamics and reversibility of folds in Langmuir monolayers.

Lipid monolayers at the air/water interface are often subject to large mechanical stresses when compressed laterally. For large enough compression they fold in the out-of-plane direction to relax stress. The repetitive folding and unfolding of lung surfactant monolayers during breathing plays a critical role in conserving monolayer material at the air/water interface lining the lung. Although the mechanisms behind the folding have been explored recently, relatively little information exists regarding the implications of folding dynamics on the long-term stability of the monolayer. We address this question by investigating the dynamical effect of folding rate in a lipid monolayer containing nano-particles, using a combination of analytic theory, simulation and experiment. We find that the presence of adsorbed particles are essential for monolayer rupture during unfolding. These particles act as linkers pinning the folds shut. The rate of folding affects reversibility as well. We construct a reversibility phase diagram spanned by the compression period and the size of the adsorbed particles showing the complex interaction of fold morphology, particle diffusion, and linker unbinding that results in reversible or irreversible folding.

Effects of topically applied heterologous serum on reepithelialization rate of superficial chronic corneal epithelial defects in dogs.

OBJECTIVE To assess the effects of topical application of undiluted heterologous serum on time to corneal reepithelialization in dogs with superficial chronic corneal epithelial defects (SCCEDs). DESIGN Multicenter, randomized, double-masked, controlled clinical trial. ANIMALS 41 client-owned dogs. PROCEDURES After collection of baseline clinical and historical data, dogs were randomly assigned to receive topically applied undiluted heterologous serum (n = 22) or isotonic saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs were performed. Ophthalmic examination including fluorescein application was performed once weekly for 4 weeks or until corneal reepithelialization. Clinicians and owners were masked to treatment group. RESULTS No differences in baseline data were detected between treatment groups. No difficulties with medication administration, noncompliance, or adverse reactions were noted. All SCCEDs in both groups healed by 4 weeks after treatment began. Median time to reepithelialization (2 weeks) was not significantly different between serum-treated and placebo-treated eyes. Irrespective of treatment group, median time to reepithelialization was not significantly different for Boxers versus non-Boxer breeds. Direct correlations were detected between time to reepithelialization and vascularization score at study entry, vascularization score at time of reepithelialization, and ulcer area at study entry in both groups. Time to reepithelialization was not correlated with age, sex, or duration of signs in either group. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to standard treatment, did not reduce time to corneal reepithelialization.