The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis

xlomafota.13 shared this article with you from Inoreader The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis Via Latest Results for Acta Neuropathologica Communications Abstract Previous studies show that 3β-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be indu ced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in β-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked to neuropathological impairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients

xlomafota.13 shared this article with you from Inoreader Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients Via Latest Results for Cardiovascular Engineering and Technology Abstract Purpose Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque. Methods We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS. Results WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1–3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01). Conclusion WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Laser‐Assisted Sialolithotripsy: A Correlation of Objective and Subjective Outcomes

xlomafota13 shared this article with you from Inoreader Laser‐Assisted Sialolithotripsy: A Correlation of Objective and Subjective Outcomes Via The Laryngoscope Objective To analyze the long-term symptomatic results of laser-assisted sialolithotripsy (LAS) in cases of obstructive sialolithiasis and correlate with objective criteria using diagnostic sialendoscopy (DS) as a method of examination. Methods This is a retrospective study comprising 50 consecutive patients who underwent holmium-YAG LAS and completed follow-up of at least 6 months. Symptom scoring and endoscopic scoring were done at 6 weeks and 6 months intervals for further study purposes. Results At the end of 6 weeks post-LAS, 70% patients were asymptomatic (A-sym) and only 30% had residual symptoms (Sym). However, obstructed duct (OB-duct) was observed on endoscopic scoring in 88% due to stenosis, residual stones, or both stenosis and residual stones. The obstructed ducts were treated in outpatient clinic and followed up over time, leading to 98% of patients being in A-sym group at the end of study period of 6 months. At the end of study, 82% of patients had clear duct (CL-duct). Conclusion Holmium LAS is a viable option for the management of intermediate-sized stones. LAS if used judiciously, and in properly selected cases, has high rate of stone fragmentation and symptom resolution. A vigilant postoperative protocol taking into account residual mealtime symptoms and altered salivary characteristics combined with early DS can help identify and treat patients with residual stone fragments and ductal stenosis. Level of Evidence 3 Laryngoscope, 2022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Coblation intracapsular tonsillectomy: a cohort study of NHS practice in England using Hospital Episode Statistics

xlomafota13 shared this article with you from Inoreader Coblation intracapsular tonsillectomy: a cohort study of NHS practice in England using Hospital Episode Statistics Via Clinical Otolaryngology Abstract Objectives To identify paediatric intracapsular Coblation tonsillectomy procedures from routine administrative data in England, and determine their safety. Design Retrospective observational cohort study of four ENT centres using routine data from Hospital Episode Statistics (HES). Setting Acute NHS trusts in England conducting exclusively intracapsular Coblation tonsillectomy Participants Children (≤16 years old) undergoing bilateral intracapsular Coblation tonsillectomy Main outcome measures Number of procedures, readmissions for pain, readmissions for bleeding and requirement for additional surgery for regrowth. Results 5525 procedures were identified. The median patient age was 4 (IQR 2-5). In-hospital complications occurred in 1%, with 0.1% returning to theatre for arrest of primary tonsil bleeding. Almost half of the procedures were conducted as a day-case (44%), with only a small proportion staying in hospital more than one night (7%). Within 28 days, 1.2% of patients were readmitted with bleeding, 0.7% with infection and 0.3% with pain. 0.2% of patients required return to theatre for control of secondary haemorrhage. Longitudinal follow-up has found that revision tonsil surgery is 0.3% at 1 year (n=4498), 1.1% at 2 years (n=2938), 1.7% at 3 years (n=1781), 1.9% at 4 years (n=905), 2.2% at 5 years (n=305) Conclusions Intracapsular coblation tonsillectomy safety outcomes in this study show primary and secondary bleed rates and emergency return to theatre rates are lower than all tonsillectomy techniques reported in the National Prospective Tonsillectomy Audit and also lower than previously published Hospital Episode Statistics analysis of tonsillectomy procedures. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Endoscopic Treatment of Sellar Arachnoid Cysts via a Simple Cyst-Opening Technique: Long-Term Outcomes From a Single Center

xlomafota13 shared this article with you from Inoreader Endoscopic Treatment of Sellar Arachnoid Cysts via a Simple Cyst-Opening Technique: Long-Term Outcomes From a Single Center Via leak of cerebrospinal fluid World Neurosurg. 2022 Feb 23:S1878-8750(22)00219-4. doi: 10.1016/j.wneu.2022.02.072. Online ahead of print. ABSTRACT BACKGROUND: Sellar arachnoid cysts (SACs) are rare lesions that require treatment only if symptomatic. The endoscopic endonasal approach has been widely used. Despite their simple cystic appearance and the straight-forward surgical intervention, important associated risks exist, with cerebrospinal fluid (CSF) leak the prevalent risk. METHODS: A retrospective analysis of patients with pathologically confirmed SAC between January 2006 and December 2019 was conducted. A homogeneous simple cyst-opening technique and skull base reconstruction with nasoseptal flaps was used. RESULTS: A total of 10 patients were identified (7 women and 3 men; median age, 54.5 years; range, 20-77 years). Of the 10 patients, 8 had had newly diagnosed SACs and 2 patients had had recurrence from a previously microsurgically fenestrated SAC. Ei ght patients had presented with visual symptoms, one with visual symptoms and fatigue, and one with intractable headaches. Neuro-ophthalmological and endocrinological assessments had revealed visual field deficits in 6, visual acuity decline in 5, and hypopituitarism in 2 patients. The median calculated volume was 1.71 mL (range, 0.27-2.54 mL). Postoperatively, no CSF leak and no further surgical complications were noted. The visual field had improved in 4 of 6 patients and visual acuity had improved in 4 of 5 patients. Anterior pituitary function had improved in 1, worsened in 1, and remained stable in 8 patients. One patient had developed diabetes insipidus. One recurrence was recorded at 54 months postoperatively. CONCLUSIONS: The results from the present study have shown that SACs can be effectively treated using a simple cyst-opening technique. The routine use of nasoseptal flaps significantly reduced the risk of CSF leakage without compromising nasal quality of life in t he long term or mandating additional incisions. Long-term follow-up is important to monitor for late recurrence. PMID:35217229 | DOI:10.1016/j.wneu.2022.02.072 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p‐NFκB and p‐STAT3 signaling pathway

xlomafota13 shared this article with you from Inoreader CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p‐NFκB and p‐STAT3 signaling pathway Via Experimental Dermatology Abstract Psoriasis is a chronic, immune mediated skin disease accompanied by hyperproliferation and inflammation of keratinocytes. Circular RNAs (circRNAs) as new players regulating the development of psoriasis have been reported in recent years. However, its mechanism has not yet been fully revealed. In this study we identified that hsa_circ_0033469 (circEIF5) was highly expressed in psoriasis tissues compared to the normal skin. We investigated the functional roles of circEIF5 in proliferation and inflammatory of HaCat cells under M5-stimulated inflammatory condition. By using a approach of knockdown and overexpression of circEIF5, we showed that circEIF5 could promote proliferation by facilitating the G1/S transition and increase secretion of chemokines in HaCat cells. These moderating effects of circEIF5 were associated with the activating of the NF-κB and STAT3 signaling pathways. Moreover, NF-κB and STAT3 inhibition abrogated circEIF5 induced promotion of cell proliferation and che mokine secretion. These results indicated that through NF-κB and STAT3 signaling pathways, circEIF5 regulated the proliferation and chemokine secretion of HaCat cells and contributed to the pathogenesis of psoriasis, which might become a potent target for psoriasis treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biodegradation of poly(L-lactic acid) and poly(epsilon-caprolactone) patches by human amniotic fluid in an in-vitro simulated fetal environment

xlomafota13 shared this article with you from Inoreader Biodegradation of poly(L-lactic acid) and poly(epsilon-caprolactone) patches by human amniotic fluid in an in-vitro simulated fetal environment Via leak of cerebrospinal fluid Sci Rep. 2022 Mar 10;12(1):3950. doi: 10.1038/s41598-022-07681-8. ABSTRACT Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid leak caused by the MMC spinal defect in the developing fetus can result in a constellation of encephalic anomalies that include hindbrain herniation and hydrocephalus. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture by progressive spinal cord damage in-utero. A randomized trial demonstrated that prenatal repair by fetal surgery, sometimes using patches, to cover the exposed spinal cord with a watertight barrier is effective in reducing the postnatal neurologic morbidity as evidenced by decreased incidence and severity of postnatal hydrocephalus and the reduced need for ventricular-peritoneal shunting. Currently, the use of inert or collagen-based patches are associated with high costs and inadequate structural properties. Specifically, the inert patches do not degrade after implantation, causing the need for a post-natal removal surgery associated with trauma for the newborn. Our present study is aimed towards in-vitro degradation studies of a newly designed patch, which potentially can serve as a superior alternative to existing patches for MMC repair. This novel patch was fabricated by blending poly(L-lactic acid) and poly(ε-caprolactone). The 16-week degradation study in amniotic fluid was focused on tracking changes in crystallinity and mechanical properties. An additional set of designed patches was exposed to phosphate-buffered saline (PBS), as a time-paired control. Crystallinity studies indicate the progress of hydrolytic degradation of the patch in both media, with a preference to bulk erosion in ph osphate buffered saline and surface erosion in amniotic fluid. Mechanical testing results establish that patch integrity is not compromised up to 16 weeks of exposure either to body fluids analog (PBS) or to amniotic fluid. PMID:35273223 | PMC:PMC8913814 | DOI:10.1038/s41598-022-07681-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.