FMR protein: Evidence of an emerging role in retinal aging?

Aging is a multifactorial process that affects the entire organism by cumulative alterations. Visual function impairments that go along with aging are commonly observed, causing lower visual acuity, lower contrast sensitivity, and impaired dark adaptation. Electroretinogram analysis revealed that the amplitudes of rod- and cone-mediated responses are reduced in aged mice and humans. Reports suggested that age-related changes observed in both rod and cone photoreceptor functionality were linked to oxidative stress regulation or free radical production homeostasis. Interestingly, several recent reports linked the fragile X mental retardation protein (FMRP) cellular activity with oxidative stress regulation in several tissue including brain tissue where FMRP participates to the response to stress via protein translation in neurite or is involved in free radical production and abnormal glutathione homeostasis. Based on these recent literatures, we raised the question about the effect of FMRP absence in the aging retina of Fmr1-/y compared to their WT littermates. Indeed, up to now, only young or adult mice (<6 months) were investigated and have shown a specific retinal phenotype. Herein, we demonstrated that Fmr1-/y mice do not present the aging effect on retinal function observed in WT littermates since ERG a- and b-waves amplitudes as well as oscillatory potentials amplitudes were not collapsed with age (12/18 months old). Absence of FMRP and its consequences seem to protect the retina against aging effect, rising a pivotal role of FMRP in retinal aging process.

[Retinal vascular network: Changes with aging and systemic vascular disease (cardiac and cerebral)]. / Caractéristiques vasculaires rétiniennes : modifications lors du vieillissement et en pathologie vasculaire systémique (cardiaque et cérébrale).

For over 10 years, the description of the retinal microvascular network has benefited from the development of new imaging techniques. Automated retinal image analysis software, as well as OCT angiography (OCT-A), are able to highlight subtle, early changes in the retinal vascular network thanks to a large amount of microvascular quantitative data. The challenge of current research is to demonstrate the association between these microvascular changes, the systemic vascular aging process, and cerebrovascular and cardiovascular disease. Indeed, a pathophysiological continuum exists between retinal microvascular changes and systemic vascular diseases. In the Montrachet study, we found that a suboptimal retinal vascular network, as identified by the Singapore I Vessel Assessment (SIVA) software, was significantly associated with treated diabetes and an increased risk of cardiovascular mortality. In addition, we supplemented our research on the retinal vascular network with the use of OCT-A. In the EYE-MI study, we showed the potential role of quantitative characterization of the retinal microvascular network by OCT-A in order to assess the cardiovascular risk profile of patients with a history of myocardial infarction. A high AHA (American Heart Association) risk score was associated with low retinal vascular density independently of hemodynamic changes. Thus, a better understanding of the association between the retinal microvasculature and macrovascular disease might make its use conceivable for early identification of at-risk patients and to suggest a personalized program of preventative care. The retinal vascular network could therefore represent an indicator of systemic vascular disease as well as an interesting predictive biomarker for vascular events.

Do tumor localization, microsatellite instability and mismatch repair deficiency have an impact on the prognosis of colorectal cancer?

BACKGROUND: Recent reports have shown that left-and right-sided colon cancers display different clinical and biological features. Chromosomal instability, epigenetic alterations, and defects in the deoxyribonucleic acid (DNA) mismatch repair (MMR) system may lead to the development of colorectal cancer (CRC). Besides microsatellite instability (MSI) caused by DNA MMR activity degradation increases the risk for CRC. AIM: We aimed to show the differences between CRCs in different locations, to research the cause of these differences, to present whether there is a relation between MMR and MSI, and to evaluate their effects on prognosis. PATIENTS AND METHODS: 641 CRC cases were divided into three groups: Group 1 (right-sided), Group 2 (left-sided), and Group 3 (rectum). Demographics, cancer stages, location of the tumors, number of the lymph nodes removed, MMR deficiency or proficiency, MSI status, and survival were assessed by retrospective review of the patients. RESULTS: Among 641 patients, 64.9% were males. Group 1, 2, and 3 comprised 31.2%, 45.7%, and 23.1% of all the cases, respectively. There was a significant difference in terms of survival and location only in stage II tumors. Stage II left colon cancer (LCCs) had a statistically significant lower survival rate. There was no significant difference in survival between both MSI and MMR statuses. In addition, cases were also stratified by stages. According to this data, 10.1, 45.7, and 44.2% of the patients had stages I, II, and III disease, respectively. CONCLUSIONS: Although it was not statistically significant, tumors with MMR deficiency (dMMR) and high microsatellite instability (MSI-H) are more common in right-sided colon tumors.

Early Endoscopy Decrease the Length of Hospital Stay and the Costs in Patients with Upper Gastrointestinal Bleeding.

BACKGROUND: Acute gastrointestinal (GI) bleeding is a common cause of hospitalization. There are conflicting results regarding the effectiveness of early endoscopy in patients with upper GI bleeding. OBJECTIVE: The study aimed to determine the benefit of early endoscopy and the epidemiological characteristics of patients presenting to the emergency department with non-variceal acute upper GI bleeding. METHODS: Patients over 18 years of age who presented to the emergency department with upper GI between 2015 and 2016 and underwent endoscopy were included in the study. The patients were divided into two groups: early endoscopy group (endoscopy within the 24 h) and late endoscopy group (endoscopy after 24 h). RESULTS: Of 104 patients, 57.7% were man, and the mean age was 66.27 ± 17.64 years. Of the patients who underwent endoscopy, 80 (76.9%) were in the early endoscopy group. There was no difference in blood transfusion needs (P = 0.388), re-bleeding (P = 0.137), the need for surgery, and mortality rates with regard to the timing of endoscopy. The results of the receiver-operating characteristics curve analysis revealed patients with a GBS ≥ 9 were taken as high-risk, and a prognosis analysis was performed accordingly. However, in patients undergoing early endoscopy, a difference was detected with respect to the length of hospital stay (P = 0.011) and treatment costs (P = 0.030). In the comparison with the admission time (working/non-working h) and variables, there were no significant differences in the length of hospital stay (P = 0.230), transfusion needs (P = 0.348), re-bleeding frequency (P = 0.905), and treatment costs (P = 0.094). CONCLUSION: Endoscopy within 24 h in the setting of acute upper non-variceal GI bleeding is associated with an increase in the length of hospital stay and treatment costs, but is not associated with re-bleeding, transfusion needs, need for surgery, and mortality.

The impact of dietary Black Soldier Fly larvae oil and meal on laying hen performance and egg quality.

Recently, the US FDA and Association of American Feed Control Officials approved Black Soldier Fly larvae (BSFL) as a feed ingredient for poultry. The objectives of this work were 1) to evaluate the nutritional profile of BSFL oil and meal in laying hens, and 2) measure the impact of the BSFL treatments on hen performance and egg quality. In 2 experiments, BSFL oil and meal were fed to replicate hens from 43 to 47 wk and from 51 to 55 wk of age. The hens were fed isocaloric, isonitrogenous diets with 3 treatment levels of BSFL oil (1.5, 3, and 4.5%, Exp. 1) or BSFL meal (8, 16 and 24%, Exp. 2). Data were analyzed by one-factor ANOVA for the main effect of diet and Tukey's multiple comparison for mean separation when significant. Exp. 1 results suggest BSFL oil could readily substituted for soybean oil with commercial hens at inclusion levels up to 4.5%. ADFI, BW, egg production, FCR, and egg weight were not impacted by the oil treatments (P > 0.05). Yolk color among hens fed the BSFL oil was greater averaging 7.88 compared to 7.37 from Control hen eggs (P = 0.0001). Exp. 2 diet formulation replaced soybean oil and meal with BSFL meal, and some additional corn was used in the higher BSFL diets. Diet amino acid balance at the highest level of inclusion (24% BSFL meal) indicates arginine and tryptophan are limiting and ADFI, BW and egg production were reduced (P < 0.05). Egg production averaged 85.14% for the Control, 8 and 16% BSFL meal hens and was significantly greater than hens fed 24% meal at 77.01%. However, 8 and 16% BSFL meal levels had no negative impact on performance and were not significantly different than the Controls. Yolk color was again higher among the meal treatments compared to the control (P = 0.0351). These experiments indicate that BSFL oil and meal can be used as dietary energy, protein and amino acids for hen maintenance, egg production and yolk coloration, although there may be upper limits of dietary inclusion.

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain.

Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.

Severe hypercalcaemia of primary hyperparathyroidism: Could giant adenoma be the real culprit rather than carcinoma?

INTRODUCTION: Hypercalcaemic crisis is a rare manifestation of hyperparathyroidism and occurs in 1.6-6% of patients with primary hyperparathyroidism (pHPT). Although such high serum calcium levels (>14mg/dl) are attributed to malignancy, it is also associated with benign disease of the parathyroid glands. The aim of this study was to evaluate the clinical features and treatment modalities of patients with severe hypercalcaemia who underwent surgery for pHPT. METHODS: The medical records of 537 patients who underwent parathyroidectomy in our department for pHPT between 2005 and 2019 were reviewed retrospectively. Twenty-four (4.4%) of the patients were described as having severe hypercalcaemia. RESULTS: Among 24 patients, 71% were female and the mean age was 55.7 years (range: 40-71 years). The mean serum calcium level at time of diagnosis was 15.9mg/dl (range: 14-22.7mg/dl). According to postoperative pathology reports, solitary adenoma, parathyroid cancer and parathyromatosis were diagnosed with the rates of 87.5%, 8.3% and 4.1% respectively. The mean weight of the solitary parathyroid lesions was 14.9g (standard deviation: 8.9g, range: 4-38g). The mean longest diameter was 2.87cm (standard deviation: 1.4cm, range: 1-5.5cm). Serum calcium levels were within the normal range on the first postoperative day in 75% of the cases. CONCLUSIONS: Severe hypercalcaemia is a rare but urgent condition of pHPT and requires prompt management. Accelerated surgery after adequate medical treatment should be performed. It is important to emphasise that giant adenoma, which is a benign disease, may be a more common cause of severe hypercalcaemia than carcinoma, unlike previously thought.

Comparative efficacy of medical treatment versus surgical sphincterotomy in the treatment of chronic anal fissure.

BACKGROUND: Anal fissure which is defined as a longitudinal tear in anoderm below the dentate line is one of the most common benign diseases of anorectal area. Severe pain during the defecation and emotional stress that it causes may reduce people's quality of life. AIMS: In this randomized clinical trial, we aimed to compare the efficiency of the topical ointment with medical treatment and surgical lateral internal sphincterotomy. METHOD: This is a randomized clinical trial of 550 patients who were treated for chronic anal fissure. Patients were randomly divided into 4 groups according to the treatment type they received. RESULTS: In a vast majority of the patients, the primary complaint was pain (92.3%) and bleeding during defecation (62%). Both pain relief and healing of the fissure, which are the components of response to treatment, had not been observed in 56 (37.3%) patients of topical nitroglycerin ointment group until the second month. Among the recalcitrant patients in both topical nitroglycerin (56) and topical diltiazem ointment (47) groups, 27 (48.2%), and 36 (76.5%) patients underwent surgery, respectively. The best response to treatment was also obtained in lateral internal sphincterotomy group. CONCLUSION: LIS is still the gold standard for the treatment of chronic anal fissure when the physicians would like to avoid recurrence and obtain the best pain relief.

Endoscopic resection for giant oesophageal fibrovascular polyp.

A fibrovascular polyp is a rare benign pseudotumour of the oesophagus and hypopharynx. Although patients usually present with dysphagia, aspiration related mortality may occur. If the tumour is too large and/or located in the proximal oesophagus, it may protrude from the mouth. The general approach to treatment is complete reconstruction with cervicotomy. We present our experience of a giant oesophageal fibrovascular polyp that was protruding from the mouth and treated with endoscopic resection. A 55-year-old man was admitted to our outpatient clinic complaining of a mass protruding from his mouth when he coughed. Endoscopy and bronchoscopy both revealed a 15-18cm long polypoid mass originating from the proximal oesophagus (at the level of the hypopharynx). Complete resection was performed via endoscopy.

House advancement flap anoplasty for severe post-hemorrhoidectomy anal stenosis.

Anal stenosis (AS), which is a very rare but serious complication, usually develops after hemorrhoidectomy. It may be mild, moderate or severe depending on the grade of stenosis. While mild and moderate types can be monitored with conservative treatment, most of the severe type require advancement flap anoplasty. There are several commonly used flap types such as Y-V, diamond and house-type flaps, but the best results belong to house-type flaps. In this paper, we aimed to present a case of severe post-hemorrhoidectomy AS, in which we performed house advancement flap anoplasty, with its video demonstrating the procedure step by step.

Diagnostic value of four-dimensional computed tomography and four-dimensional magnetic resonance imaging in primary hyperparathyroidism when first-line imaging was inadequate.

INTRODUCTION: Accurate localisation of the abnormal hyperfunctioning gland with preoperative imaging has a critical role in parathyroid surgery to obtain a successful outcome. This study aimed to evaluate the diagnostic performance of second-line imaging and their contribution to the treatment success in primary hyperparathyroidism when the first-line methods were negative or discordant. METHODS: Among the patients who underwent parathyroidectomy due to primary hyperparathyroidism, 33 who underwent four-dimensional computed tomography and/or four-dimensional magnetic resonance imaging because of negative or discordant first-line imaging results were included. Persistent and recurrent cases were excluded. RESULTS: The majority of the patients were female (84.8%) and the mean age was 59.2 years. Seventeen patients had four-dimensional computed tomography and 25 had four-dimensional magnetic resonance imaging, respectively. Four-dimensional computed tomography and four-dimensional magnetic resonance imaging localised the culprit gland successfully in 52.9% and 84%, respectively. Twenty-five patients in whom single adenoma was detected underwent focused parathyroidectomy. The culprit gland was solitary in 32 cases and one patient had double adenoma. Normocalcaemia was achieved in all cases. Among the 29 patients who completed their postoperative sixth month success rate was 100%. CONCLUSION: Four-dimensional magnetic resonance imaging had high accuracy with fast dynamic imaging in detecting parathyroid adenomas. When the first-line imaging methods were negative or inconclusive, four-dimensional magnetic resonance imaging should be considered primarily since it is cost effective in Turkey and emits no radiation.

Frequency of psychiatric disorders in nonemergent admissions to emergency department.

OBJECTIVES: Repeated admissions of patients with undiagnosed psychiatric problems in emergency departments (ED) is a major contributor to patient unsatisfaction and overcrowding in EDs. We evaluated the presence of psychiatric disorders in non-emergent admissions in the ED of a tertiary care hospital. MATERIALS AND METHODS: This cross-sectional study was carried out in Eskisehir Osmangazi University Hospital between December 2015 and March 2016. The study group consists of 4320 non-emergent patients (31% of all admissions to non-emergent ED). Psychiatric assessments of patients were done using the Primary Care Evaluation of Mental Disorders (PRIME-MD) scale prior to their discharge from the ED. The Mann-Whitney U, Kruskal-Wallis and Chi-square tests, as well as multivariate logistic regression, were performed for statistical analysis. RESULTS: The mean age was 30 ± 11.7 years years ranging from 18 to 78 years. Among non-emergent cases, 44% had at least one psychiatric disorder. The most frequent psychiatric disorder was mood disorder (major and minor depression). Females with a comorbid disease and lower education level had increased risk for mood disorders, anxiety disorders, and somatoform disorders. Single males with a comorbid disease had increased risk for alcohol dependence. CONCLUSIONS: Undiagnosed patients with psychiatric disorders appear to be frequent users of medical emergency department services. These results might be helpful in developing more effective strategies to serve the mental health needs of the undiagnosed. People's awareness of psychiatric disorders should be increased.

Retrospective evaluation of adult poisoning cases admitted to emergency department of a University Hospital in Turkey.

OBJECTIVE: We aimed to evaluate demographic, etiological, clinical features, and prognosis of poisoning cases applied to a tertiary emergency department retrospectively. MATERIALS AND METHODS: The recordings of poisoning cases aged 18 years old and over which applied to the department of emergency medicine between the dates of 2010-2015 were examined. Age, gender, admission date, amount of time passed since exposure to the poisonous substance, application method, cause of poisoning, laboratory findings at arrival, vital signs, type of poisonous substance, the way of taking, treatment method in urgent care, consultation need, and the outcome of cases were recorded. RESULTS: Of the poisoning cases, 437 (52.1%) were female, and 402 (47.9%) were male. The mean age was calculated as 33.50. When the cause of poisonings are examined; 456 patients were found to be poisoned by a suicide attempt, 350 were accidentally poisoned, and 33 were poisoned by treatment complication. As the causing substance of poisoning, medicinal drugs were found in 465 cases (55.4%), carbon monoxide in 205 cases (24.4%), and narcotics in 119 cases (14.2%). Of medicinal drug poisonings, 221 (46.8%) were multiple drug intake. It was seen that 46.6% of the patients were kept under observation with only symptomatic treatment while nasogastric lavage and activated charcoal were applied in 40.2% of them. CONCLUSION: It can be suggested that poisonings are encountered more commonly in young people, especially in women, with medicinal drugs and for suicidal purposes. Drugs detected at high rates in poisonings, such as painkillers and antidepressants, should be used more cautiously.