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Abstract Background Let-7 microRNAs (miRNAs) may contribute to neurodegeneration, including Alzheimer's disease (AD), but, they were not investigated in Streptozotocin (STZ)-induced AD. Letrozole increases the expression of Let-7 in cell lines, with conflicting evidence regarding its effects on memory. This study examined Let-7 miRNAs in STZ-induced AD, their correlation with memory and hyperphosphorylated Tau (p-Tau) and the effects of Letrozole on them. Methods Seven groups of adult Sprague Dawley rats were used: Negative control, Letrozole, Letrozole Vehicle, STZ (with AD induced by intracerebroventricular injection of STZ in artificial cerebrospinal fluid (aCSF)), CSF Control, STZ + Letrozole (STZ-L), and CSF + Letrozole Vehicle. Alternation percentage in T-maze was used as a measure of working memory. Let-7a, b and e and p-Tau levels in the hippocampus were estimated using quantitative real-time reverse transcription–polymerase chain reaction (qRT–PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results Significant decreases in alternation percentage and increase in p-Tau concentration were found in the STZ, Letrozole and STZ-L groups. Expression levels of all studied microRNAs were significantly elevated in the Letrozole and the STZ-L groups, with no difference between the two, suggesting that this elevation might be linked to Letrozole administration. Negative correlations were found between alternation percentage and the levels of all studied microRNAs, while positive ones were found between p-Tau concentration and the levels of studied microRNAs. Conclusions This study shows changes in the expression of Let-7a, b and e miRNAs in association with Letrozole administration, and correlations between the expression of the studied Let-7 miRNAs and both the status of working memory and the hippocampal p-Tau levels. These findings might support the theory suggesting that Letrozole aggravates pre-existing lesions. They also add to the possibility of Let-7’s neurotoxicity.

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.

Aims. Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. Methods. Adult female albino rats (n=100) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. Results. (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy (p

Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling.

Postinfectious glomerulonephritis (PIGN), a form of immune complex GN, is not well-defined in HIV-infected patients. This study characterizes PIGN in this patients' population and determine the impact of histopathological patterns on renal outcome and mortality.HIV-infected patients with PIGN from September 1998 to July 2013 were identified. Archived slides were reviewed by a blinded renal pathologist, classified into acute, persistent and healed PIGN. Groups were compared using Wilcoxon rank-sum and Fisher's exact test. Survival analyses were performed to determine association of histopathological pattern with renal outcome and mortality.Seventy-two HIV-infected predominantly African American males were identified with PIGN. Median (interquartile range) age and creatinine at the time of renal biopsy was 48 years (41, 53) and 2.5 mg/dl (1.5, 4.9) respectively. Only 2 (3%) had acute PIGN, 42 (58%) had persistent PIGN and 28 (39%) had healed PIGN. Three patients (4%) had IgA-dominant PIGN. Only 46% of the patients had confirmed positive cultures with Staphylococcus the most common infectious agent. During a median follow up of 17 months, the pathological pattern had no impact on renal outcome (P = 0.95). Overall mortality was high occurring in 14 patients (19%); patients with healed PIGN had significantly increased mortality (P = 0.05).In HIV-infected patients, Staphylococcus is the most common cause of PIGN. Renal outcome was not influenced by the histopathological pattern but those with healed PIGN had greater mortality which was potentially due to a confounder not accounted for in the study.

Background: Epilepsy is one of the most common diseases of the central nervous system that leads to seizures and neurobiological, cognitive, and social consequences. Studies have shown that vitamin D has a critical role in brain development and neuroprotection. According to another study, exercise effectively improves a variety of brain functions. Objective: The current work is designed for the assessment of the beneficial effects of vitamin D and exercise in a rat model of epilepsy disease. Materials and Methods: 30 healthy adult male albino rats were divided equally into five groups: the control group, the epilepsy-induced group by pentylentetrazole, the epileptic group with vitamin D, the epileptic group with exercise, and the epileptic group with both vitamin D and exercise. The following parameters were assessed in rat brain tissues: BDNF and GABA. Serum levels of IL-1β, MDA, TNF-α, GSH, and GABA were also estimated in addition to cognitive function tests and histopathological examination of rat brain tissues. Results: In the epileptic group, there was a significant increase in IL-1β, TNF-α, and MDA levels. In addition to a significant decrease in GSH, GABA, and BDNF levels. Treatment with either vitamin D or exercise significantly improved biochemical abnormalities, cognitive dysfunction, and the histopathological picture of the brains of epileptic rats, with the best results in the combined vitamin D and exercise-treated group. Conclusions: These data suggest that combined vitamin D and exercise could be considered as a potential and effective line for treating epilepsy disease. [ABSTRACT FROM AUTHOR]

Background: Letrozole is an aromatase inhibitor with conflicting studies reporting its effects on memory in male and female animals, and whether the observed memory impairments become exacerbated with an additional insult such as Alzheimer's disease (AD); an illness in which beta-amyloid and hyperphosphorylated Tau (p-Tau) protein accumulate. We examined Letrozole effects on memory, hippocampal p-Tau and histopathology in animals treated with Letrozole only or on top of induced AD, and investigated whether there would be any sexbased differences in memory status and/or p-Tau. Methods: Fifty-one adult male and female Sprague Dawley rats were divided into: Control groups: Intact, Letrozole Vehicle, CSF, and CSF+Letrozole Vehicle, Letrozole group, Streptozotocin (STZ) group; with induced AD via cerebroventricular STZ injection in artificial CSF and, STZ+Letrozole (STZ-L) group. Memory was tested in a T-maze to measure alternation percentage. Hippocampal p-Tau protein levels were estimated using ELISA, and histopathology was documented in sections stained with Hematoxylin and Eosin. Results: There were significant reductions in alternation percentage in the STZ, Letrozole and STZ-L groups; most severe in the STZ-L group and least severe in the Letrozole group. Significant elevation in p-Tau concentration was observed in the STZ, Letrozole and STZ-L groups compared to the controls. No differences were found between males and females in all groups in any of the studied parameters. Histopathological examination showed neurodegeneration and inflammation in the Letrozole, STZ and STZ-L groups. Conclusions: Letrozole alters memory, more so in experimentally-induced AD, increases p-Tau and may cause hippocampal pathological changes, with no sex-based differences. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones have shown to affect mitochondrial oxidative activity, synthesis of protein, and differentiation of muscle fibers and capillary growth. the aim of the current study is to explore the effect of experimentally induced thyroid dysfunction (hyperthyroidism, hypothyroidism) on IL6 levels and some of oxidative stress markers in order to clarify some of underlying possible mechanisms, and link these events with metabolic and histological changes. Methods: Thirty adult male albino rats (fed ordinary laboratory along this 4 weeks' study), were divided randomly into 3 equal groups; control group, experimentally-induced hypothyroid group this group (rats received a single daily dose of 2 mg carbimazole/100g body weight diluted in drinking water by oral gavage for 4 weeks) and experimentallyinduced hyperthyroid group (rats received L-thyroxin at a dose of 2µg/ml diluted in drinking water for 4 weeks). At the end of the experiment body mass index (BMI) were estimated for all rats. Results: There was statistical significant difference between hypothyroidism, hyperthyroidism and control groups as regard oxidative stress markers and thyroid hormones levels; also, there was a statistical significant increase in serum interleukin-6 (IL-6) and serum tumor necrosis factor alpha (TNF-a) in both hypothyroidism and hyperthyroidism groups. There was a significant positive correlation between serum IL-6 with serum insulin and TNF-a with malondialdehyde (MDA). Conclusions: hypothyroidism and hyperthyroidism were associated with the deterioration of serum IL-6 and TNF-a, and impairment of oxidation state. These data provide new insights into the role the antioxidant defense system and the use of various supplements to improve thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Aims. Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. Methods. Adult female albino rats (n = 100) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. Results. (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy (p < 0.05 each). (2) Combined treatment significantly improved medial gastrocnemius electromyographic amplitude and sciatic function index compared to pregabalin monotherapy (p < 0.05 each). (3) Combined treatment significantly increased the BDNF expression, decreased anti-inflammatory cytokine (p < 0.05 each), and restored the structural nerve damage, compared to pregabalin monotherapy. Conclusions. Combined treatment is associated with greater improvement of the sciatic nerve structure and function. Further studies are warranted to study the mechanism of action of the combined treatment to improve neuropathic pain. [ABSTRACT FROM AUTHOR]