Autophagy and the endolysosomal system in presynaptic function

xlomafota.13 shared this article with you from Inoreader Autophagy and the endolysosomal system in presynaptic function Via Latest Results for Cellular and Molecular Life Sciences Abstract The complex morphology of neurons, the specific requirements of synaptic neurotransmission and the accompanying metabolic demands create a unique challenge for proteostasis. The main machineries for neuronal protein synthesis and degradation are localized in the soma, while synaptic junctions are found at vast distances from the cell body. Sophisticated mechanisms must, therefore, ensure efficient delivery of newly synthesized proteins and removal of faulty proteins. These requirements are exacerbated at presynaptic sites, where the demands for protein turnover are especially high due to synaptic vesicle release and recycling that induces protein damage in an intricate molecular machinery, and where replacement of material is hampered by the extreme length of the axon. In this review, we will discuss the contribution of the two major pathways in place, autophagy and the endolysosomal system, to presynaptic protein turnover and presynaptic function. Although clear ly different in their biogenesis, both pathways are characterized by cargo collection and transport into distinct membrane-bound organelles that eventually fuse with lysosomes for cargo degradation. We summarize the available evidence with regard to their degradative function, their regulation by presynaptic machinery and the cargo for each pathway. Finally, we will discuss the interplay of both pathways in neurons and very recent findings that suggest non-canonical functions of degradative organelles in synaptic signalling and plasticity. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anatomical basis of erector spinae plane block: a dissection and histotopographic pilot study

xlomafota.13 shared this article with you from Inoreader Anatomical basis of erector spinae plane block: a dissection and histotopographic pilot study Via Latest Results for Journal of Anesthesia Abstract Purpose Erector spinae plane (ESP) block is an interfascial blockade used in different clinical scenarios. This study investigated the ventral extent of dye diffusion in ESP block. Methods The ultrasound-guided ESP block was bilaterally performed with an injection at the T5 vertebral level (21-Gauge, 50 mm needle), using diluted black tissue marking dye (20 mL; 1:4 ratio with standard saline solution) instead of local anesthetic on two fresh-frozen corpses within the body donation program of the University of Padova. Subsequently, the gross anatomical dissection was performed by a combined posterior plus anterior approach, and the histotopographic examination completed. Results Macroscopically by gross anatomical dissection, the dye spreading ranged on the dorsal side of the chest from T2/3 to T10/11 with an extension up to 10 cm laterally, and on the ventral side of the chest from T2/3–T9/10. Microscopically by histotopographic examination, the dye diffused ventrally to the intercostal spaces (2–3 and 5–6 spaces on the right and left, respectively) by following the blood vessels coupled to the dorsal nerve passing through the costotransverse foramen. Conclusions The anterior pathway of dye diffusion from the site of injection within the erector spinae muscle group during an ESP block seems to follow the blood vessels and dorsal rami of spinal nerves, suggesting the passing through the costotransverse foramen to reach the anterior paravertebral space and the intercostal nerves. These findings display an anterior histotopographic diffusion of dye resembling a paravertebral block. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Topical Probiotics in Dermatological Therapy and Skincare: A Concise Review

xlomafota.13 shared this article with you from Inoreader Topical Probiotics in Dermatological Therapy and Skincare: A Concise Review Via Latest Results for Dermatology and Therapy Abstract Recent studies have produced an increasing body of evidence that the intestinal microbiome plays an essential role in modulating systemic inflammation and skin diseases. The gut microbiome influences and modulates the host immune system, enabling immune tolerance of environmental and dietary antigens and protecting against pathogens. Emerging scientific evidence has demonstrated that oral probiotics can help treat certain skin diseases, such as acne, atopic dermatitis, photoaging, psoriasis, and wound healing. The aim of this paper is to review the current scientific evidence on topical probiotics and their effects on dermatological diseases and skincare and to clarify if the application of exogenous probiotics could also have the same benefit as oral probiotics in promoting positive bacterial balance to treat dermatologic conditions. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Surgical management of symptomatic cavum septum pellucidum cysts: systematic review of the literature

xlomafota.13 shared this article with you from Inoreader Surgical management of symptomatic cavum septum pellucidum cysts: systematic review of the literature Via Latest Results for Neurosurgical Review Abstract Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are commonly found incidentally. They are usually asymptomatic but may present with symptoms related to obstructive hydrocephalus. There is no consensus about the management of symptomatic CSP and CV cysts. We present, to the best of our knowledge, the first systematic review of the different treatment options for symptomatic CSP and CV cysts. We conducted a literature review using PubMed database, searching for cases of symptomatic CSP and CV cysts managed surgically, and published until April 2019. Preoperative characteristics, surgical procedure, and postoperative outcome were analyzed using SPSS® software (Statistical Package for Social Sciences, IBM®). We found 54 cases of symptomatic CSP and CV cysts managed surgically (34 males, 20 females, 1.7/1 male to female ratio). Mean age was 24.3 ± 20.1 years. The most common presentation was headaches (34 patients, 62%), followed by psychiatric s ymptoms (27 patients, 49.1%). Preoperative radiological hydrocephalus was present in 30 patients (54.5%). The most common surgical procedure was endoscopic fenestration (39 patients, 70.9%), followed by shunting (10 patients, 18.2%), open surgery (3 patients, 5.5%), and stereotactic fenestration (1 patient, 1.8%). Complete resolution of symptoms was achieved in 36 patients (65.5%) and partial resolution in 7 patients (12.7%), and symptoms were unchanged in 2 patients. The present review suggests that surgical treatment could provide resolution of the symptoms in most of the cases, regardless of the procedure performed. Although mean follow-up was short among the studies, recurrence rate was low. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Possible tics diagnosed as stereotypies in patients with severe autism spectrum disorder: a video-based evaluation

xlomafota.13 shared this article with you from Inoreader Possible tics diagnosed as stereotypies in patients with severe autism spectrum disorder: a video-based evaluation Via Latest Results for Neurological Sciences Abstract Background The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications. Methods A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity. Results Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01). Conclusions Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role and function of Chondrostereum purpureum in biocontrol of trees

xlomafota.13 shared this article with you from Inoreader Role and function of Chondrostereum purpureum in biocontrol of trees Via Latest Results for Applied Microbiology and Biotechnology Abstract A decay fungus, Chondrostereum purpureum (Pers. Ex Fr.) Pouzar, has been investigated in Europe, Northern America and New Zealand for its ability to decay hardwood stumps and thus prevent sprouting. The aim of these investigations has been to find an alternative to mechanical (cutting only) and chemical sprout control (cutting and applying chemicals to stumps in order to prevent sprouting). Mechanical sprout control is not an efficient option due to hardwood tree species' ability to re-sprout efficiently after cutting, and therefore management costs are high. Chemicals would be efficient but due to their harmful effects on the environment, alternatives are needed. The fungal treatment, i.e., cutting accompanied with C. purpureum inoculum is an environmentally friendly and efficient option for sprout control. This mini-review comprises the role and function of C. purpureum in biocontrol of trees: the ecology of C. purpureum, its sprout control efficacy, factors affecting sprout control efficacy, devices in biological sprout control, potential risks, and the future perspectives of biological sprout control. Key points • A fungus Chondrostereum purpureum is efficient in preventing sprouting of hardwoods • C. purpureum is not sensitive to environmental conditions • Devices should be developed for cost-efficient biological sprout control View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury

xlomafota.13 shared this article with you from Inoreader Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury Via Latest Results for Acta Neurochirurgica Abstract Background The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). Methods High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 μmol/L. S-thiopental concentrations and administered doses were registered. Results Seventeen children treated with BCT 2007–2017 with high-resolution data were included; median age 15 (range 6–17) and median Glasgow coma score 7 (range 3–8). Median time from trauma to start of BCT was 44.5 h (range 2.5–197.5) and from start to stop 99.0 h (range 21.0–329.0). Median ICP was 22 (IQR 20–25) in the half hour period before onset of BCT and 16 (IQR 11–20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62–71) and 63 (57–71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1–0.7), in the half hour period 5 h later 0.3 (IQR 0.1–0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2–0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). Conclusion BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures

xlomafota.13 shared this article with you from Inoreader Naltrexone's Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures Via Latest Results for Advances in T... Abstract Background Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN. Methods A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies. Results Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3–5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy. Conclusion This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies

xlomafota.13 shared this article with you from Inoreader Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies Via Latest Results for Advances in T... Abstract Introduction Cefprozil, an oral second-generation semi-synthetic cephalosporin, possesses a broad spectrum of antimicrobial activity. A granule formulation has been developed to improve medication adherence of the patients. This study was conducted to assess the bioequivalence of the granule formulation to a dry suspension in healthy Chinese volunteers and estimate the pharmacokinetic (PK) profiles of cefprozil. Methods An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 60 healthy Chinese volunteers under fasted or fed conditions (30 volunteers for each condition) to assess the bioequivalence between two formulations of cefprozil. Blood samples were collected at specified time intervals, and the plasma concentrations of cis- and trans-cefprozil were determined by a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events (AEs) were also recorded. Results Under fasted conditions, the mean Cmax was (3534.70 ± 634.67) ng/ml, Tmax was (0.98 ± 0.25) h, t1/2 was (1.37 ± 0.13) h and AUC0-t was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean Cmax was (2438.80 ± 493.78) ng/ml, Tmax was (1.66 ± 0.76) h, t1/2 was (1.36 ± 0.24) h and AUC0-t was (9332.36 ± 1373.61) ng·h/ml, respectively. The PK parameters of the granule formulation of cefprozil were similar to those of the suspension. The 90% CI values of the GMRs of Cmax, AUC0-t and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence range (80.00–125.00%). Conclusions According to the criteria for bioequivalence, the test granule formulations of cefprozil and "Cefprozil for Suspension®" were determined to be bioequivalent whether under fasted or fed conditions by measurement of cis-, trans- and total cefprozil. Trial registration ClinicalTrials.gov identifier, NCT04414254. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease

xlomafota.13 shared this article with you from Inoreader Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease Via Latest Results for Clinical Drug Investigation Abstract Background and Objectives Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD. Methods We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score. Results Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group. Conclusions The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond

xlomafota.13 shared this article with you from Inoreader Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond Via Latest Results for Cellular and Molecular Life Sciences Abstract Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding o f neuronal function during development, adulthood and in neurodegeneration. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.