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BackgroundThe provision of eye care services is currently insufficient to meet the requirements of eye care. Many people remain unnecessarily visually impaired or at risk of becoming so because of treatable or preventable eye conditions. A lack of access and awareness of services is, in large part, a key barrier to handle this unmet need. ObjectiveThis study aimed to assess whether utilizing novel smartphone-based clinical algorithms can task-shift eye screening to community volunteers (CVs) to accurately identify and refer patients to primary eye care services. In particular, we developed the Peek Community Screening app and assessed its validity in making referral decisions for patients with eye problems. MethodsWe developed a smartphone-based clinical algorithm (the Peek Community Screening app) using age, distance vision, near vision, and pain as referral criteria. We then compared CVs’ referral decisions using this app with those made by an experienced ophthalmic clinical officer (OCO), which was the reference standard. The same participants were assessed by a trained CV using the app and by an OCO using standard outreach equipment. The outcome was the proportion of all decisions that were correct when compared with that of the OCO. ResultsThe required sensitivity and specificity for the Peek Community Screening app were achieved after seven iterations. In the seventh iteration, the OCO identified referable eye problems in 65.9% (378/574) of the participants. CVs correctly identified 344 of 378 (sensitivity 91.0%; 95% CI 87.7%-93.7%) of the cases and correctly identified 153 of 196 (specificity 78.1%; 95% CI 71.6%-83.6%) cases as not having a referable eye problem. The positive predictive value was 88.9% (95% CI 85.3%-91.8%), and the negative predictive value was 81.8% (95% CI 75.5%-87.1%). ConclusionsDevelopment of such an algorithm is feasible; however, it requires considerable effort and resources. CVs can accurately use the Peek Community Screening app to identify and refer people with eye problems. An iterative design process is necessary to ensure validity in the local context.

Background/Objective: Leishmaniasis is the second deadliest parasitic disease in the world, after malaria, with an estimated 1.6 million new cases each year. While cutaneous leishmaniasis can result in permanent scars from lesions after treatment, the mucocutaneous and visceral diseases can result in life-altering and life-threatening complications. Accurate species diagnosis is critical for treatment and follow-up, and while PCR-based diagnostics can provide sensitive parasite detection and species identification, they are slow, expensive, and not suitable for low-resource settings. In this publication, we describe our efforts to develop a simple, affordable, and instrument-free Leishmania DNA diagnostic that can be used in both high-tech settings and the field. Methods: Computational biology was utilized to design region-targeted RPA oligos and the corresponding CRISPR guides for the detection of all Leishmania species as well as the specific identification of L. (V.) panamensis as a predictor of mucocutaneous disease. Then, we executed systematic approaches for parasite lysis, RPA amplification of DNA, and fluorescent CRISPR crRNA detection. Results: We have demonstrated the ability to detect single-digit parasites without compromising the specificity in identifying single species as the proof of concept for a point-of-care diagnostic. Individual assays were carried out in succession, culminating in an unquenched fluorescent signal quantifiable over negative control. Conclusions: The described work is the foundation which will be implemented into a three-track [all Leishmania, mucocutaneous or visceral only, and a human positive control] assay that we plan to utilize in a Funnel Adapted Sensing Tube (FAST) single use, instrument-free, and affordable diagnostic. [ABSTRACT FROM AUTHOR]

We examined the extent to which apnoea‐induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra‐elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end‐apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri‐iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015–0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative–nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S‐nitrosohaemoglobin consumption and plasma S‐nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative–nitrosative stress. Key points: Local sampling of blood across the cerebral circulation in ultra‐elite apnoeists determined the extent to which severe end‐apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical‐mediated nitric oxide bioavailability and global cerebral bioenergetic function.Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative–nitrosative stress.The apnoea‐induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose.Cerebral oxidative–nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea‐induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia.This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production. [ABSTRACT FROM AUTHOR]

Platelets are known primarily for their role in blood clotting; however, it is becoming clear that they play diverse roles beyond that of haemostasis. Exercise has been shown to activate platelets and stimulate neurogenesis, neuroplasticity and improve cognitive function, highlighting a potentially powerful link between platelet function and brain health. Despite this clear link between platelets and the brain, very little is known about the behaviour of platelets through the cerebral circulation in humans. We examined platelet concentration across the brain in exercising humans at sea level (340 m) and high altitude (6–8 days at 3800 m; a stimulus known to modify platelet function). During intense exercise at sea level, platelet concentration increased similarly by 27 ± 17% in the arterial and internal jugular venous circulations (exercise: P < 0.001, interaction: P = 0.262), indicating no uptake or release of platelets into/from the brain. At high altitude, resting platelet concentrations were similar to sea level values in both the arterial and jugular venous circulations (P = 0.590); however, intense exercise at high altitude caused a 31 ± 35% decrease in platelet concentration across the brain (P = 0.016). This divergent response across the brain was not observed in any other haematological or metabolic variables. These data highlight a unique situation where the combination of intense exercise and high altitude hypoxia cause a decrease in platelet concentration across the cerebral circulation. The physiological implications and mechanisms that might influence platelet function across the brain during exercise at high altitude remain to be established. Key points: Platelets are known primarily for their role in blood clotting; however, it is becoming clear that they play diverse roles beyond that of haemostasis.Exercise has been shown to activate platelets, which in turn stimulate neurogenesis, neuroplasticity and improve cognitive function, highlighting a powerful link between platelet function and brain health.At sea level, platelet concentration in blood going into and out of the brain was similar at rest, during maximal exercise and in recovery from exercise.During maximal exercise at high altitude, platelet concentration was 31% lower in the blood exiting the brain; the final destination of these platelets is unknown.The physiological implications and mechanisms that might influence platelet function across the cerebral circulation during exercise at high altitude remain to be established. [ABSTRACT FROM AUTHOR]