Corneal Sensitivity Is Inversely Correlated With Severity of Diabetic Retinopathy in a Predominantly Underrepresented Population.

PURPOSE: To assess the relationship between diabetic retinopathy (DR) and corneal sensitivity. METHODS: In this prospective study, 100 eyes of 50 patients from primarily underrepresented racial and ethnic backgrounds with DR underwent assessment of corneal sensitivity using a Cochet-Bonnet esthesiometer. Severity of DR was graded by a masked reading center. Corneal sensitivity was compared in eyes with current or regressed proliferative DR (PDR) (n=35) and eyes with nonproliferative DR (NPDR) with no history of PDR (n=65). Corneal sensitivity in eyes that regressed from PDR to NPDR with anti-vascular endothelial growth factor (anti-VEGF) therapy (n=7) was compared to treatment-naïve eyes with no current or prior PDR (n=55) and to eyes with newly diagnosed, treatment-naïve PDR (n=12). RESULTS: In eyes with current or prior PDR, the median corneal sensitivity (average of 4 quadrants) was 0.5 cm (interquartile range [IQR] 0-3.375), whereas in eyes with no current or prior PDR, the median corneal sensitivity was 4.75 cm (IQR 2.0-6.0, P < .0001). The median corneal sensitivity in eyes with regressed PDR was 0 cm (IQR 0-0.875), significantly lower than eyes with no current or prior PDR (4.5 cm, IQR 4.0, P = .0076) and no different than eyes with untreated PDR (0 cm, IQR 1.25). The odds of eyes with DR severity scale score ≥60 having complete corneal sensitivity loss was 3.6 times that of eyes with NPDR. CONCLUSIONS: Corneal sensitivity is impaired in eyes with PDR compared to NPDR and is not rescued by anti-VEGF therapy. Assessment of corneal sensitivity in eyes with DR may identify patients at risk for additional complications, including neurotrophic keratopathy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Deep-learning models for the detection and incidence prediction of chronic kidney disease and type 2 diabetes from retinal fundus images.

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min-1 per 1.73 m2 and 0.65-1.1 mmol l-1, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.

A deep-learning pipeline for the diagnosis and discrimination of viral, non-viral and COVID-19 pneumonia from chest X-ray images.

Common lung diseases are first diagnosed using chest X-rays. Here, we show that a fully automated deep-learning pipeline for the standardization of chest X-ray images, for the visualization of lesions and for disease diagnosis can identify viral pneumonia caused by coronavirus disease 2019 (COVID-19) and assess its severity, and can also discriminate between viral pneumonia caused by COVID-19 and other types of pneumonia. The deep-learning system was developed using a heterogeneous multicentre dataset of 145,202 images, and tested retrospectively and prospectively with thousands of additional images across four patient cohorts and multiple countries. The system generalized across settings, discriminating between viral pneumonia, other types of pneumonia and the absence of disease with areas under the receiver operating characteristic curve (AUCs) of 0.94-0.98; between severe and non-severe COVID-19 with an AUC of 0.87; and between COVID-19 pneumonia and other viral or non-viral pneumonia with AUCs of 0.87-0.97. In an independent set of 440 chest X-rays, the system performed comparably to senior radiologists and improved the performance of junior radiologists. Automated deep-learning systems for the assessment of pneumonia could facilitate early intervention and provide support for clinical decision-making.

Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles.

Alpha-synuclein (α-syn) is localized in cellular organelles of most neurons, but many of its physiological functions are only partially understood. α-syn accumulation is associated with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy as well as other synucleinopathies; however, the exact pathomechanisms that underlie these neurodegenerative diseases remain elusive. In this review, we describe what is known about α-syn function and pathophysiological changes in different cellular structures and organelles, including what is known about its behavior as a prion-like protein. We summarize current knowledge of α-syn and its pathological forms, covering its effect on each organelle, including aggregation and toxicity in different model systems, with special interest on the mitochondria due to its relevance during the apoptotic process of dopaminergic neurons. Moreover, we explore the effect that α-syn exerts by interacting with chromatin remodeling proteins that add or remove histone marks, up-regulate its own expression, and resume the impairment that α-syn induces in vesicular traffic by interacting with the endoplasmic reticulum. We then recapitulate the events that lead to Golgi apparatus fragmentation, caused by the presence of α-syn. Finally, we report the recent findings about the accumulation of α-syn, indirectly produced by the endolysosomal system. In conclusion, many important steps into the understanding of α-syn have been made using in vivo and in vitro models; however, the time is right to start integrating observational studies with mechanistic models of α-syn interactions, in order to look at a more complete picture of the pathophysiological processes underlying α-synucleinopathies.

SNPs and other polymorhisms associated with acaricide resistance in Rhipicephalus microplus.

Ixodicides resistance of ticks is one of the most important problems for the livestock industry in tropical and subtropical regions, mainly due to the increase in cases of multiple resistance in all families of the ixodicides used. Molecular markers such as single nucleotide polymorphisms (SNPs) has been proposed to identify the resistance to ixodicides in Rhipicephalus microplus. Many studies have recently been conducted using SNPs and other types of molecular markers to determine if they are associated with resistance to different products in many parts of the world. Knowing these changes at the molecular level, will allow to establish mechanisms and control strategies for the use of ixodicides. In this review, we will discuss and describe the different SNPs and other polymorphisms associated with resistance in R. microplus.

Field challenge of cattle vaccinated with a combined Babesia bovis and Babesia bigemina frozen immunogen.

To determine the optimal dose of a combined, frozen immunogen containing in vitro culture-derived strains of Babesia bovis and Babesia bigemina, twenty-four 14-month-old Bos taurus steers from a Boophilus microplus-free area in Northern Mexico were used in this experiment. Cattle were randomly allocated into six groups with four animals each, and were intramuscularly inoculated as follows: group 1 (control animals) were administered with normal bovine erythrocytes; group 2 received 1 x 10(7) B. bovis- and B. bigemina-infected erythrocytes as a combined fresh immunogen. Groups 3-6 were inoculated with a combined frozen immunogen containing (previous to cryopreservation at -196 degrees C) 1 x 10(7), 5 x 10(7), 1 x 10(8), and 5 x 10(8) infected erythrocytes of each parasite species, respectively. Four months after immunization, principal and control animals were translocated to a bovine babesiosis endemic zone for field challenge. This was carried out by introducing the experimental cattle to tick-infested pastures for 30 days without ixodicide treatment. Cattle were monitored from day 8 postintroduction to the field (PIF) by recording the manifestation of clinical disease, rectal temperature values (RT), packed cell volume index (PCV), and percent of parasitized erythrocytes (PPE). At challenge, all experimental cattle became infected with both Babesia bovis and B. bigemina. However, except for two animals from group 6, none of the vaccinated animals showed signs of acute clinical babesiosis; therefore, no treatment was instituted. Out of six animals showing acute clinical babesiosis (four group 1 controls and two group 6 vaccinates), two animals (one from each group) died, despite babesiacide treatment, as they manifested classical cerebral babesiosis caused by B. bovis. Regardless of the dose or type of immunogen used (combined fresh or frozen), 90% of vaccinated cattle were determined to be protected against the virulent Babesia sp. field isolates. Nevertheless, by evaluating clinical parameters, such as average of maximum drop in PVC index (28.5%), average duration of parasitemia (3 days for B. bovis; 8.5 days for B. bigemina), and average duration of RT values > or = 39.5 degrees C (2 days), animals receiving 1 x 10(8) infected erythrocytes, as combined frozen immunogen, were more efficaciously protected against challenge with virulent B. bovis and B. bigemina field isolates.