Liraglutide, 7,8-DHF and their co-treatment prevents loss of vision and cognitive decline in a Wolfram syndrome rat model.

Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and is characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, and learning difficulties. GLP1 receptor agonist liraglutide and BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF) have had protective effect to visual pathway and to learning and memory in different rat models of neurodegenerative disorders. Although synergistic co-treatment effect has not been reported before and therefore the aim of the current study was to investigate liraglutide, 7,8-DHF and most importantly for the first time their co-treatment effect on degenerative processes in WS rat model. We took 9 months old WS rats and their wild-type (WT) control animals and treated them daily with liraglutide, 7,8-DHF or with the combination of liraglutide and 7,8-DHF up to the age of 12.5 months (n = 47, 5-8 per group). We found that liraglutide, 7,8-DHF and their co-treatment all prevented lateral ventricle enlargement, improved learning in Morris Water maze, reduced neuronal inflammation, delayed the progression of optic nerve atrophy, had remyelinating effect on optic nerve and thereby improved visual acuity in WS rats compared to WT controls. Thus, the use of the liraglutide, 7,8-DHF and their co-treatment could potentially be used as a therapeutic intervention to induce neuroprotection or even neuronal regeneration.

Electrocardiographic findings of methanol toxicity: a cross-sectional study of 356 cases in Iran.

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.

Serum oxidized low-density lipoprotein level as a marker of oxidative stress in patients undergoing hyperbaric oxygen therapy.

OBJECTIVE: Oxidative stress (OS) is involved in the pathogenesis of atherosclerosis. Hyperbaric oxygen therapy (HBOT), in which 100% oxygen is inhaled under hyperbaric pressure, may create OS. Therefore, the aim of this research was to measure the serum oxidized low-density lipoprotein (oxLDL) level in patients undergoing HBOT. METHODS: Twenty-nine patients who underwent HBOT to treat various diseases were enrolled in this study. The serum oxLDL level was measured at the beginning of the first and after the 10th therapy session. RESULTS: There was no significant difference between the oxLDL level of patients before and after HBOT (4.96±0.1 vs. 4.94±0.1 U/mL; p=0.36). CONCLUSION: HBOT seems to be safe in terms of oxLDL production up to 10 sessions. However, further large-scale studies investigating longer duration of HBOT treatment are required to understand the role of OS.

Serological Measures of Trachoma Transmission Intensity.

Ocular infection with Chlamydia trachomatis can lead to trachoma, a leading infectious cause of blindness. Trachoma is targeted for elimination by 2020. Clinical grading for ocular disease is currently used for evaluating trachoma elimination programs, but serological surveillance can be a sensitive measure of disease transmission and provide a more objective testing strategy than clinical grading. We calculated the basic reproduction number from serological data in settings with high, medium, and low disease transmission based on clinical disease. The data showed a striking relationship between age seroprevalence and clinical data, demonstrating the proof-of-principle that age seroprevalence predicts transmission rates and therefore could be used as an indicator of decreased transmission of ocular trachoma.

Homocysteine serum levels in diabetic patients with non proliferative, proliferative and without retinopathy.

Homocysteine has been associated with extracellular matrix changes. The diabetic retinopathy is a neurovascular complication of diabetes mellitus and it is the leading cause of vision loss among working adults worldwide. In this study, we evaluate the role of homocysteine in diabetic retinopathy analyzing the plasma levels of homocysteine in 63 diabetic type 2 patients with nonproliferative retinopathy (NPDR), 62 patients with proliferative diabetic retinopathy (PDR), 50 healthy subjects used as control group, and 75 randomly selected patients.

A liver abscess deprived a healthy adult of eyesight: endogenous endophthalmitis associated with a pyogenic liver abscess caused by serotype K1 Klebsiella pneumonia.

Klebsiella pneumonia usually causes urinary tract infections, pneumonia, and other infectious diseases in hospitalized and immunocompromised patients. Among the types of Klebsiella pneumonia, serotype K1 is known to be a highly virulent pathogen. We herein report the case of a healthy 63-year-old man with a pyogenic liver abscess and bilateral endogenous endophthalmitis caused by serotype K1 Klebsiella pneumonia. Although the patient received percutaneous abscess drainage and antibiotic therapy, he lost his eyesight. To improve the poor prognoses of ocular complications, providing both an earlier diagnosis and treatment is critical.

Vitamin a deficiency in pregnancy: perspectives after bariatric surgery.

This study aims to describe the clinical consequences of vitamin A deficiency (VAD) in pregnant women after bariatric surgery. Included are studies on VAD during pregnancy and after bariatric surgery conducted in humans from 1993 to 2011. There are few investigations on the relationship between pregnancy and bariatric surgery and on the damage to the binomial mother-child resulting from VAD in this relationship. The high percentage of VAD in the postoperative period is a cause for concern, especially considering the function of this vitamin in certain biological moments and in moments of intense nutritional demand. This vitamin serum evaluation is recommended during the prenatal period.

Effects of biomarkers of oxidative stress damage on prevalence and severity of visual disability among black Central Africans.

BACKGROUND: Because of the demographic transition, lifestyle changes, urbanization, and nutrition transition, Central Africans are at higher risk of ocular diseases associated with oxidative stress and visual disability. This study aimed to estimate the normal values of oxidant status defined by oxidized low-density lipoprotein (Ox-LDL), 8-Isoprostane and 8-hydroxy-deoxyguanosine (8-OHdG) and to determine their pathogenic role in the prevalence and the severity of visual disability among these black Africans. METHODS: This was a cross-sectional study, run in a case-control study randomly selected from Kinshasa province, DR Congo. The study included 150 type 2 diabetes mellitus (T2DM) patients (cases) matched for sex and age to 50 healthy non diabetic controls. Logistic regression models were used to identify independent determinants of visual disability. RESULTS: The presence rates were 8.5% for blindness, 20.5% for visual impairment and 29% for visual disability including blindness and visual impairment. After adjusted for taro leaves intake, red beans intake, T2DM, aging, waist circumference, and systolic blood pressure, we identified low education level (OR=3.3 95%CI 1.5-7.2; p=0.003), rural-urban migration (OR=2.6 95% CI 1.2-5.6; p=0.017), and high Ox-LDL (OR=2.3 95% CI 1.1-4.7; p=0.029) as the important independent determinants of visual disability. After adjusted for education, intake of red beans, intake of taro leaves, triglycerides, and T2DM, we identified no intake of safou fruit (OR=50.7 95% CI 15.2-168.5; p<0.0001), rural-urban migration (OR=3.9 95%CI 1.213; p=0.012), and high 8-OHdG (OR=14.7 95% CI 3.9-54.5; p<0.0001) as the significant independent determinants of visual disability. After adjusted for education level, no intake of red beans, no intake of Taro leaves, triglycerides, and T2DM, we identified no intake of Safou fruit (OR=43.1 95% CI 13.7-135.4; p<0.0001), age ≥ 60 years (OR=3.4 95% CI 1.3-9; p=0.024), and high 8-Isoprostane (OR=11 95% CI 3.4-36.1; p<0.0001) as the significant independent determinants of visual disability. CONCLUSIONS: Visual disability remains a public health problem in Central Africa. Antioxidant supplement, fruit intake, nutrition education, control of migration, and blocking of oxidative stress are crucial steps for delayed development of vision loss.

Revisiting Diabetes 2000: challenges in establishing nationwide diabetic retinopathy prevention programs.

PURPOSE: To evaluate the impact of the Diabetes 2000 program, an initiative launched by the American Academy of Ophthalmology in 1990 to improve nationwide screening of diabetic retinopathy (DR) and to reduce the prevalence and severity of the condition. DESIGN: Retrospective, observational case study of Diabetes 2000 program. METHODS: This is a perspective piece with a review of literature and personal opinions. RESULTS: Patients with diabetes are likely to see an increase in the disease burdens associated with DR unless effective programs for early detection and control of DR are implemented. CONCLUSIONS: Despite recent efforts to educate both patients and physicians alike about the importance of routine DR screening, the lessons learned from the Diabetes 2000 program illustrate the need for new strategies capable of improving accessibility to high-quality eye care, increasing involvement of primary care physicians in DR screening and encouraging at-risk individuals to seek testing.

Biological risk of older adults with visual impairments.

OBJECTIVES: To investigate whether biological markers of health differ among older adults with visual impairment compared to those with normal vision. DESIGN: We use data from the National Health and Nutrition Examination Survey (1999 - 2006) to investigate clinically defined at-risk levels for 10 biological markers. SETTING: Survey participants were non-institutionalized. PARTICIPANTS: Nationally representative (U.S.) sample of older adults age 65 and older, categorized as having blindness (20/200 or worse), low vision (20/40 to 20/100) or normal vision (better than 20/40). INTERVENTION: Separate binary logistic regressions (one for each biomarker, with two at-risk cut points for BMI: obese and underweight) were computed to determine the odds of having at-risk levels of each biomarker. MEASUREMENTS: Biomarkers included: systolic and diastolic blood pressure, high-density lipoprotein, low-density lipoprotein (LDL) cholesterol, total cholesterol, glycated hemoglobin, body mass index (BMI), fasting triglycerides, C-reactive protein, and plasma homocysteine. RESULTS: Older adults who were blind were more likely to have high-risk levels of LDL cholesterol, homocysteine, and to be underweight (BMI>18.5). Similarly, older adults with LV were more likely to have high-risk levels of homocysteine compared to older adults with normal vision. CONCLUSION: As several of the high-risk biomarkers associated with visual impairment were diet-related, our results suggest the importance of nutrition and diet programs aimed towards educating older people who are visually impaired.

Increased regional homogeneity of blood oxygen level-dependent signals in occipital cortex of early blind individuals.

Although resting-state functional magnetic resonance imaging has shown altered functional connectivity between visual and other brain areas in the early blind individuals, it cannot answer which brain area's local activities are changed. In this study, regional homogeneity, a measure of the homogeneity of the local blood oxygen level-dependent signals, was used for the first time to investigate the changes in the resting-state brain activity in the early blind individuals. Compared with age-matched and sex-matched sighted individuals, the early blind individuals showed increased regional homogeneity only in the occipital areas, which might be explained by the abnormal cortical development and/or experience-dependent plasticity, resulted from an early visual deprivation.

Genetic analysis of Lrp5 function in osteoblast progenitors.

The low-density lipoprotein receptor-related protein (Lrp)-5 regulates osteoblast proliferation and bone formation through its expression in duodenum by modifying the gut serotonin-bone endocrine axis. However, its direct role, if any, in osteoblast progenitor cells has not been studied thus far. Here, we show that mice with a Dermo1-Cre-mediated disruption of Lrp5 in osteoblast progenitor cells have normal embryonic skeletogenesis and normal skeletal growth and development postnatally. Histomorphometric analysis of 3-month-old adult mice revealed normal osteoblast numbers, bone formation rate, and bone mass in Lrp5(Dermo)(-/-) mice. In addition, analysis of two osteoporosis pseudoglioma (OPPG) patients revealed a three- to fivefold increase in their serum serotonin levels compared to age-matched controls. These results rule out a direct function of Lrp5 in osteoblast progenitor cells and add further support to the notion that dysregulation of serotonin synthesis is involved in bone mass abnormalities observed in OPPG patients.

Sudden-onset blindness in sickle cell disease due to retinal artery occlusion.

Central retinal artery occlusion (CRAO) is a rare and potentially devastating cause of acute blindness in sickle cell disease (SCD) that is unique compared to classic sickle retinopathy. Few details related to this complication in SCD are known, including its risk factors, pathogenesis, presentation, treatment and outcomes. We present three patients with SCD and retinal artery occlusion. The overall variability in clinical presentation, treatment and prognosis reported in the literature underscores the need for a greater understanding of these factors as they relate to this complication in SCD.

Prognostic factors in methanol poisoning.

The aim of this study was to assess the clinical and laboratory factors in methanol poisoned patients to determine the prognosis of their toxicity. This survey was done as a prospective cross-sectional study in methanol-poisoned patients in Loghman-Hakim hospital poison center during 9 months from October 1999-June 2000. During this time 25 methanol-poisoned patients were admitted. The mortality rate was 12 (48%). Amongst survivors, three (23%) of the patients developed blindness due to their poisoning and the other 10 (77%) fully recovered without any complication. The mortality rate in comatose patients was nine (90%) while in non-comatose patients it was three (20%) (P<0.001). There was a significant difference in mean pH in the first arterial blood gas of patients who subsequently died (6.82+/-0.03) and survivors (7.15+/-0.06) (P<0.001, M-W). The mean time interval between poisoning and ED presentation in deceased patients were (46+/-15.7) hours, in survived with sequelae were (16.7+/-6.7) and in survived without sequelae were (10.3+/-7.2) hours (P<0.002, K-W). We found no significant difference between the survivors versus the patients who died regarding methanol. Simultaneous presence of ethanol and opium affected the outcome of the treatment for methanol intoxication favourably and unfavourably, respectively. In our study, poor prognosis was associated with pH<7, coma on admission and >24 hours delay from intake to admission.