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Glucagon-like peptide-1(GLP-1) is a multifunctional polypeptide throughout the lifespan via activating Glucagon-like peptide-1 receptor (GLP-1R).GLP-1 can affect food ingestion, enhance the secretion of insulin from pancreatic islets induced by glucose and be utilized to treat type 2 diabetes mellitus(T2DM).But, accumulating evidences from the decades suggest that activation GLP-1R can not only regulate the blood glucose, but also sustain the homeostasis of intracellular environment and protect neuron from various damaged responses such as oxidative stress, inflammation, excitotoxicity, ischemia and so on. And more and more pre-clinical and clinical studies identified that GLP-1 and its analogues may play a significant role in improving multiple central nervous system (CNS) diseases including neurodegenerative diseases, epilepsy, mental disorders, ischemic stroke, hemorrhagic stroke, traumatic brain injury, spinal cord injury, chronic pain, addictive disorders, other diseases neurological complications and so on. In order to better reveal the relationship between GLP-1/GLP-1R axis and the growth, development and survival of neurons, herein, this review is aimed to summarize the multi-function of GLP-1/GLP-1R axis in CNS diseases.

The primary objective of this study was to examine if people with protein C deficiency, which is a natural anticoagulant and also an endogenous acyl ghrelin peptidase, have elevated circulating levels of acyl ghrelin. The clinical trial was conducted in a university hospital setting. People with protein C deficiency were identified and invited to participate by a specialized coagulation outpatient clinic. People with protein C deficiency were examined and compared to age, sex, and body mass index matched healthy controls with regards to acyl ghrelin, unacylated ghrelin, growth hormone (GH) and insulin-like growth-factor I (IGF-I) in a cross-sectional case-control study. Systemic levels of acyl ghrelin, desacyl ghrelin, acyl-to-desacyl ghrelin ratio, GH and IGF-I were similar in people with protein C deficiency and healthy controls. Despite a significant reduction of protein C in people with protein C deficiency, there was no difference in acyl ghrelin or the secondary end points unacylated ghrelin, GH, or IGF-I in people with protein C deficiency.

Despite the development of new antiseizure drugs (ASDs), around one third of epilepsy patients become refractory to treatment or experience adverse events due to ASDs. Therefore, discovery of new ASDs and new therapy options are crucial to improve the quality of life. Herein, we report a 3-year-old child with multi-drug resistant epilepsy caused by perinatal asphyxia whose seizures were reduced by 90% after the introduction of ketogenic diet, vagal nerve stimulation (VNS) AspireSR (SR-seizure response) and oral cannabidiol.

Compensatory changes in cervical sagittal alignment after C1-C2 arthrodesis have been reported in a few studies. No studies have explored the differences in these compensatory changes between traumatic and non-traumatic pathologies. Conflicting reports exist on the correlation between cervical sagittal parameters and neck pain or function.Medical records of 81 consecutive patients [Jan 2010-Dec 2018] who underwent Harms arthrodesis were retrospectively reviewed. 53 patients were included in the final analysis. Radiological parameters [C0-C1, C1-C2, C2-C7 angles and T1 slope] and clinical parameters [VAS (Visual analogue scale) and NDI (Neck disability index)] were compared between the two groups, Group A (traumatic) and Group B (non-traumatic).The 53 patients [Group A (The sub-axial sagittal profile was strongly correlated with the ΔC1-C2 angle in both groups. Group B showed greater changes in sagittal parameters after Harms fixation and Group A showed greater improvement in long-term functional outcomes. The final functional outcomes were not related to the initial or final radiological sagittal profile in both groups.

Background Verrucous carcinoma is a rare mucocutaneous malignancy characterized by slow, relentless growth and a low metastasis rate. Objective Herein we summarize surgical success rates and review newer approaches to the treatment of verrucous carcinomas.Methods & Materials: PubMed electronic searches were performed by B.F. and C.V. using combinations of the following terms: ''verrucous carcinoma,'' ''Ackerman tumor,'' ''Buschke Lowenstein,'' ''epithelioma cuniculatum,'' ''carcinoma cuniculatum,'' ''papillomatosis cutis,'' ''treatment,'' ''therapeutics,'' ''management,'' ''mohs surgery,'' and ''excision.'' A systematic review was conducted on 49 articles in accordance with PRISMA guidelines. Results Surgical management remains first-line therapy. Wide local excision is most commonly utilized, with highly variable margins (0.5-3.0 cm) and recurrence rates (4.6-75.0%). Mohs Micrographic Surgery has also been used, especially for recurrent tumors, with an overall recurrence rate of 12.9%. Conclusion Surgery is the treatment of choice, either by Mohs Micrographic Surgery or wide local excision. However, surgical recurrence rates are high, and tissue-sparing therapies are desirable given the sensitive locations involved. Ultimately, randomized control trials are needed to develop evidence-based guidelines for the management of VCs.

Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac-renal-vasculature dysfunction. A 'cytokine storm' namely, interleukin IL6-IL1 receptors i.e. IL6R-IL1R over-functioning was reported. Here, nigellidine, an indazole-alkaloid and key-component of Nigella Sativa L. (NS) commonly known as black-cumin-seed was analyzed for COVID-19 protein-targeting and IL1R-IL6R inhibition through molecular-docking-study and biochemical-study in experimental-rat to evaluate antioxidative-capacity. The NMR/X-ray-crystallographic/Electron-microscopic structures of COVID-19 Main-protease (6LU7)/Spike-glycoprotein(6vsb)/NSP2(QHD43415_2)/Nucleocapsid(QHD43423), Human IL1R(1itb)-IL6R(1pm9) from PDB were retrieved-analyzed for receptor-ligand interaction. Then those structures were docked with nigellidine using Autodock and Patchdock-server. A brief comparison was made with nigellicine-thymoquinone from N. sativa. Where nigellidine showed highest binding-energy of -6.6 (kcal/mol), ligand-efficiency of -0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding-pocket. Nigellidine showed strong interaction with main-protease (BE:-6.38/LE:-0.29). Nigellidine showed affinity to IL1R (-6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde(MDA) than the basal-levels. From the Western-blot and activity-analysis it was observed that Nigellidine (sulfuryl-group-drug) showed no impact on Phenol-catalyzing ASTIV and Steroid-catalyzing estrogen-sulfotransferase expressions and activities in liver-tissue and thus has no influence in sulfation-mediated adverse metabolic-processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit-potentials of COVID-19 proteins. Further validation is necessary.

Laser hair removal has become popular means of achieving hair reduction with improved quality of life.This study aimed to assess the safety and efficacy of Multipass low fluence, high-frequency 755-nm Alexandrite laser versus the high fluence, low-frequency 1064-nm long-pulsed Nd: YAG laser on axillary hair reduction in women with dark skin phototypes.This study was carried out on 30 adult women [skin type, IV-VI)] who seek axillary hair reduction. These subjects were adjusted to receive 5 laser sessions with a 1-month interval. One side received high fluence, low-frequency 1064-nm laser where the other side received multipass low fluence, high-frequency 755 nm laser. The follow-up was done using photographs, folliscope, patients' visual analog pain scale.The mean percentage of hair density reduction showed significant improvement in both treated sides being higher in the Alex treated side with corresponding significant decreases in the mean hair thickness.Multipass low fluence, high-frequency 755-nm Alex laser practice was verified to be safe and effective for hair removal in dark skin phototypes compared to the high fluence, low frequency 1064-nm long-pulsed Nd:YAG laser.

1. The following trial investigated the antigout activity and probable mechanism of Piper betle L. herb in gout-induced broiler chickens. The antioxidant and production performance modulating activity of P. betle L. was compared against the standard antigout drug Allopurinol.2. One hundred and sixty, one-day-old female chicks were randomly divided into five treatment groups (control, gout challenged, Allopurinol, P. betle 20 g/kg and P. betle 25 g/kg of feed) with eight birds per group (four replicates) and fed over six weeks. Gout was induced using sodium bicarbonate in water (20 g/l). The clinical signs of gout and production performance were recorded and gross and histopathology was conducted on dead birds. Serum uric acid and creatinine were estimated (on d 10, 14, 17, 19, 21 and 42) and antioxidant and xanthine oxidase enzyme activities were measured from blood samples.3. Uric acid progressively reduced after treatment with P. betle 20 g/kg from d 17 (19.4 ± 0.7 mg/dl) to d 21 (9.81 ± 0.3 mg/dl) and xanthine oxidase activity was likewise suppressed (7.80 ± 0.04 U/mg protein), in a similar manner to Allopurinol (7.75 ± 0.05 U/mg protein), which authenticated the mechanism of antigout activity. Better feed conversion ratios (1.83 ± 0.001) and the restoration of the antioxidants superoxide dismutase, catalase and glutathione to normal levels were observed from birds fed P. betle 20 g/kg than with Allopurinol.4. The data showed that P. betle can be an effective treatment for gout in broiler chicken, as an alternative to Allopurinol.

Contact lens have been proposed as a mean of ocular drug delivery, but the conventional soaking method to load hydrophobic drugs, such as latanoprost shows low drug loading and high burst release with alteration in the critical lens properties. In this paper, a novel latanoprost-loaded PEGylated solid lipid nanoparticles (LP-pSLNs) were developed to increase the latanoprost loading capacity of contact lenses (LP-pSLN-L), while also sustaining ocular drug delivery. The pSLNs were spherical in shape with an average size of 105‒132 nm (nanometer) and a zeta potential ranging from ‒29.1 to ‒26.7 mV (millivolt). The LP-pSLNs led to improved swelling, transmittance, and protein adherence of the lens compared to the non-pegylated SLNs congeners (LP-SLN-L) and conventional soaked lens (LP-SM-L). The LP-SM-L lens showed low drug loading, high burst release, and a short release duration of 24 h. The LP-SLN-L and LP-pSLN-L lenses showed high drug uptake and sustained drug release up to 120 h and 96 h, respectively. The pegylation reduced the size of nanoparticles and improved the drug loading capacity, while the release rate was high in the initial hours. The LP-pSLN-L lens was found to be safe based in histopathological studies. In animal studies, the LP-pSLN-10-L batch showed high drug concentration at all-time points up to 96 h compared to the LP-SM-L and eye drop solution. In conclusion, pSLNs improved the latanoprost loading in the contact lens and showed sustained drug release, and thus can be used as a substitute to eye drop therapy.

PURPOSE The aim of this study was to determine whether glaucoma patients after trabeculectomy could benefit more from subconjunctival injections of bevacizumab than 5-FU or placebo. METHODS AND RESULTS Fifty-one eyes of 51 patients were recruited for primary MMC (0.2mg/ml for 1 min) augmented trabeculectomy. 17 patients were randomly assigned to receive 1.25mg (0.05ml) of bevacizumab augmentation, 21 patients were assigned to receive 0.1ml of 50mg/ml 5-FU and 13 patients were assigned to a control group receiving a normal saline injection as a placebo. Initial recruitment included 58 patients, but seven patients had to be excluded from the study for various reasons. Postoperative follow up of IOP and bleb characteristics was carried out at 1 day, 1 week, 3 weeks, 6 weeks, 6 months and 1 year after surgery. All analyses where carried out by two masked clinicians. IOP reduction was statistically significant (P

INTRODUCTION Recurrent pericarditis (RP) is a debilitating disease that has an underlying autoinflammatory pathophysiology mediated by cytokine interleukin (IL)-1. Rilonacept, a recombinant dimeric fusion protein that blocks IL-1α and IL-1β signaling has emerged as a valuable therapeutic option of RP. Rilonacept has been evaluated in Phase 2 and 3 clinic trials and was recently approved for RP treatment. AREAS COVERED This article reviews available clinical trials assessing the efficacy and safety of rilonacept for the treatment of RP. EXPERT OPINION Findings from Rhapsody (Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY) phase 2 and 3 trials suggest that rilonacept represents a promising new therapy for those patients with colchicine resistant or glucocorticoid-dependence disease. Treatment leads to rapid clinical response, with a median resolution of symptoms in 5 days, normalization of C-reactive protein (CRP) in a median of 7 days, and successful weaning from glucocorticoids. This novel therapy also reduces recurrence rates compared with placebo. Rilonacept has also demonstrated a good safety profile, with the most common adverse events including injection-site reactions and upper respiratory tract infections. This anti-IL 1 agent has emerged as an efficacious treatment for RP, with potential use for glucocorticoid-free regimens and as monotherapy. Future trials are needed to explore these treatment options and to clarify the appropriate therapy duration.

Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field.The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations.Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

1. This study investigated the effects of dietary betaine supplementation on growth performance, meat quality, muscle fatty acid composition and antioxidant ability in slow-growing broiler chickens. 2. In total, 400, one-day-old female Xueshan broiler chicks were randomly divided into five groups with eight replicates of ten chickens each for 102 days. Broilers were fed a basal diet supplemented with 0, 125, 250, 500 or 1,000 mg/kg betaine. 3. Broilers fed betaine had better feed conversion efficiency and weight gain (P

Chemotherapy is a traditional treatment method in clinical cancer treatment. However, it is limited due to the large toxic side effects of chemotherapeutics. Nanomedicines have shown great potential in the application of tumor therapy. The size of nanoparticles as a crucial factor in the enhanced permeability and retention (EPR) effect can be regulated for the enhanced chemotherapy. Therefore, we believe that regulation of nanoparticle size can be used as an effective sensitizer to enhance the therapeutic effect of chemotherapy drugs on tumors. Here, we prepared several nanoparticles of different hydrodynamic diameters commonly found in nanomedical applications by the diblock copolymer of methoxy polyethylene glycol-poly ($$\epsilon $$‐caprolactone) (mPEG-PCL). The blood circulation effect and organ distribution in blood were detected by fluorescence labeled nanoparticles. We found that the small-sized nanoparticles exhibited much longer blood circulation time than the large-sized nanoparticles in vivo, and thus the nanoparticle concentration in the tumor tissue was relatively high. Systematic injection of the doxorubicin (DOX) loaded nanoparticles can effectively inhibit tumor growth. Compared to the free drug, tumor cells were much more sensitive to DOX loaded nanoparticles of small size. Our nano-drug delivery system has been proven to be safe and nontoxic in vivo and was suitable for use as a sensitizer in clinical oncology chemotherapy.

ABSTRCTThe α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction, especially immunotherapy response prediction, remains unclear in liver cancer. Through the tumour-free survival (TFS) and overall survival (OS) rates analyses of serum AFP and sICAM-1 levels in 87 patients with primary hepatocellular carcinoma (HCC), the patients whose AFP and sICAM-1 levels were normal (AFP < 20 μg/L or sICAM-1 < 1000 μg/L) before surgery or recovered to normal after surgery exhibited a lower tumour recurrence rate and better OS than patients with elevated serum levels of the two markers. Combined analysis showed that patients with synchronously elevated levels of AFP and sICAM-1 showed the lowest TFS and OS. In addition, the RNA-seq data and clinical information of The Cancer Genome Atlas Liver Hepatocellular Carcinoma were collected to analyse the predictive values of AFP and ICAM-1 in the diagnosis, prognosis and immunotherapy of HCC. The results indicated that the combined application of the two indicators had higher accuracy in both the diagnosis and prognostic prediction of HCC by receiver operating characteristic curves. AFP and ICAM-1 were significantly correlated with multiple immune cells in HCC samples but not in normal samples. The patients with low expression of the two indicators were most likely to benefit from the immune checkpoint blockade therapy. In conclusion, AFP and ICAM-1 play vital roles in the diagnosis, prognostic prediction, and immunotherapy of HCC, suggesting that they are considered as prognostic predictors in clinical practice.

The current drugs for the treatment of type 2 diabetes mellitus (T2DM) can cause side effects after long-time use. Hence, the novel drugs were urgent need to developed for T2DM patients. In this study, the effect of astragalus polysaccharide on dysfunctional insulin cells was investigated to clarify whether astragalus polysaccharide could be a novel drug for T2DM treatment. MIN6 cells (mouse pancreatic β-cell line) were treated with high glucose (HG)+ palmitic acid (PA) and then treated with astragalus polysaccharide. The proliferation, apoptosis, and insulin secretion were measured using CCK8, flow cytometry, and ELISA, respectively. Pancreatic and duodenal homeobox 1 (PDX1), miR-136-5p, and miR-149-5p expression levels were measured by RT-qPCR. The combination of EF-hand domain family member 2 (EFHD2) and miR-136-5p or miR-149-5p was analyzed by luciferase reporter assay. EFHD2 protein level was measured by western blot. We found that HG+PA treatment reduced MIN6 cell viability, insulin secretion, and PDX1 expression and promoted MIN6 cell apoptosis. Astragalus polysaccharide treatment reversed the effect of HG+PA on MIN6 cells. Additionally, astragalus polysaccharide treatment promoted miR-136-5p and miR-149-5p expression. Silencing of miR-136-5p and miR-149-5p expression partially reversed the therapeutic effects of astragalus polysaccharide. Furthermore, EFHD2 was the target of miR-136-5p and miR-149-5p. Meanwhile, astragalus polysaccharide treatment inhibited EFHD2 protein level in HG+PA treated MIN6 cell. Finally, EFHD2 overexpression partially reversed the therapeutic effects of astragalus polysaccharide. In conclusion, astragalus polysaccharide treatment improved proliferation and insulin secretion in HG+PA-treated MIN6 cells partially by promoting miR-136-5p and miR-149-5p expression to inhibit EFHD2 expression.

Introduction Local recurrence (LR) is one of the main pitfalls in surgery for extremities soft tissue sarcoma (eSTS). Achieving clear histopathological margins is the most important factor to reduce the risk of LR, but the ability to do so depends on not only surgical technique but also the interplay between tumour biology, anatomical location and surgical approach. The balance between postoperative morbidity and oncological benefits in reducing the risk of LR needs to be considered. Areas covered This review will cover which aetiological factors for the development of eSTS lead to an increased risk of LR and discuss histological subtypes that have a high risk of LR and which surgical and neoadjuvant therapeutic strategies can minimise the risk of LR. Expert opinion The traditional view that surgical radicality always results in low rates of LR, while marginality alone always leads to high rates of relapse, is outdated. In the modern era of surgical oncology, limb salvage and high-level function after resectional surgery are the key surgical goals. The best results are achieved by combining effective neoadjuvant treatments with planned bespoke oncological operations that consider the biological and anatomical factors of each individual sarcoma.

OBJECTIVE This study examined the accuracy of hearing aid output to DSL v5.0 Child targets in a group of children who wear hearing aids, and the impact on their auditory outcomes. DESIGN For each participant, the output of the initial hearing aid fitting was compared to DSL v5.0 Child prescriptive targets and again after the fitting was adjusted using coupler-based verification and RECD measures. Outcomes for initial and adjusted fittings were examined using the Speech Intelligibility Index (SII), Parent's Evaluation of Aural/Oral Performance of Children (PEACH) rating scale, and speech perception tests in quiet and noise. STUDY SAMPLE Sixty-eight children aged 3 months to 17 years with moderate to profound hearing loss participated in the study. RESULTS Fit-to-targets improved significantly after hearing aids were adjusted to match targets to within 5 dB RMSE. Adjusted hearing aids provided increased aided audibility compared to initial fittings and resulted in improved speech perception scores and parent-reported hearing performance. Fifty percent of the children aged 6 to 17 years preferred their adjusted fitting compared to 10% who preferred their initial fitting. CONCLUSIONS Improvement in fit-to-target to a validated paediatric prescriptive formula using best practice procedures can result in improved auditory outcomes and possible self-reported satisfaction.

INTRODUCTION The Ovation ALTO is the next generation aortic stent graft from Endologix for the treatment of infra-renal abdominal aortic aneurysms. The device uses polymer-injected rings to create a proximal seal at the aneurysm neck. AREAS COVERED Results from the first clinical study of the ALTO graft are analysed and the potential benefits of the graft in minimising post-treatment aneurysmal neck dilation discussed. The implications of the ALTO's Instructions-For-Use (IFU) and low-profile delivery system are also reviewed. EXPERT OPINION The re-positioning of the sealing rings higher on the graft and an integrated compliant balloon are the most significant improvements on the Ovation iX, facilitating accurate placement of the proximal sealing ring and prompt balloon dilation of the polymer rings. The expansion the IFU to include neck lengths of ≥ 7mm will mean more patients are eligible for infra-renal EVAR within IFU with the ALTO device. The published data on the device to date is limited. With over 1000 implants worldwide we would hope for more published data to become available. If this demonstrates similar mid-term results to that seen with the Ovation iX in arguably more hostile neck anatomy, then the Ovation ALTO is likely to be more widely used.

Introduction Venetoclax has transformed the treatment landscape in hematologic malignancies, especially in elderly population. With high rates of remission, deep and durable responses, and safe toxicity profile, venetoclax in combination therapy has been extremely effective, garnering accelerated approval and becoming standard of care in lymphoid and myeloid malignancies. Areas covered The role of venetoclax in the intrinsic apoptotic pathway is covered. This includes preclinical and clinical experience of venetoclax monotherapy and combination therapy in relapsed/refractory and frontline CLL, AML, ALL and high-risk MDS, with an emphasis on key clinical trials and efficacy of combination regimens in distinct mutational landscapes. Strategies to mitigate myelosuppression, manage dose adjustments and infectious complications are addressed. Expert opinion Targeting BCL-2 offers a safe and highly effective adjunct to available therapies in hematologic malignancies. Despite success and frequent utilization of venetoclax, several resistance mechanisms have been elucidated, prompting development of novel combinatorial strategies. Further, on-target myelosuppression of venetoclax is a key obstacle in clinical practice, requiring diligent monitoring and practice-based knowledge of dose modifications. Despite these limitations, venetoclax has gained tremendous popularity in hematologic-oncology, becoming an integral component of numerous combination regimes, with ongoing plethora of clinical trials encompassing standard chemotherapy, targeted agents and immune-based approaches.

Myelofibrosis is a myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells, bone marrow fibrosis and cytopenias, extramedullary hematopoiesis and hepatosplenomegaly, increased pro-inflammatory cytokine production, and systemic symptoms. Patients with MF also have a propensity toward leukemic transformation. Allogeneic hematopoietic stem cell transplantation (aHCT) is the only curative therapy for patients with MF; however, transplant-related morbidity and mortality precludes this option for the majority of patients. In the last decade, two targeted therapies have been approved for the treatment of MF, both JAK2 inhibitors, ruxolitinib and fedratinib. Despite the clinical efficacy of these two compounds in terms of splenomegaly and symptom burden reduction, there remain many areas of unmet need in the treatment of myelofibrosis. In this review, we discuss the limitations of currently approved treatment options and novel therapeutic targets with drug candidates in late-stage (phase II or III) clinical development for the treatment of MF. We delve into the mechanism of action and scientific rational of each candidate agent as well as the available clinical data, and ongoing trials that could lead to the approval of some of these novel therapies.

Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable.Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM-1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio.Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; ηp2 = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml-1; PLA Δ = 0.92 ± 0.44 ng ml-1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43).Conclusion: Acute low-dose (0.3 g kg-1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation.Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; VO2max: Maximal Oxygen Uptake.Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood.Acute high-dose (0.9 g kg FFM-1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation.This study examined the efficacy of low-dose (0.30 g kg FFM-1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20-30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military.Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

Morphine tolerance poses a great challenge for clinicians, whose pathogenesis has a close connection with microglial activation and neuroinflammation. Dihydroartemisinin (DHA) that derives from artemisinin, may serve as a potential anti-inflammatory drug. In this study, the effects as well as the underlying mechanism of DHA on suppressing microglial activation and neuroinflammation were explored. The microglial cell line BV-2 cells were induced by morphine and treated with DHA or minocycline. With the application of CCK-8, the cell viability was detected. Western blot was employed to assess the expressions of Ki67, IBa-1, and TLR4 and quantitative real-time PCR (qRT-PCR) was adopted to evaluate miRNA-16 (miR-16) expression. With the adoption of ELISA kits and qRT-PCR, the release of inflammatory cytokines was evaluated. Besides, luciferase reporter assay was applied to testify the binding relationship between miR-16 and TLR4. NF-κB expression was measured by immunofluorescence. DHA reduced cell viability and decreased protein expression of Ki67 and IBa-1 in morphine-induced BV-2 cells. Additionally, DHA contributed to the declined release of pro-inflammatory cytokines. miR-16 was down-regulated by morphine but was up-regulated by DHA concentration-dependently in BV-2 cells. The inhibition of miR-16 partly abolished the inhibitory effects of DHA on morphine-induced microglial activation and neuroinflammation. Moreover, TLR4 was found to be bound to miR-16, and the inhibitory effect of DHA on TLR4/NF-κB was partly reversed by miR-16 inhibition. In conclusion, DHA remarkably suppressed microglial activation and neuroinflammation through regulating miR-16-mediated TLR4/NF-κB signaling. This study may provide a new solution to improve clinical analgesic efficacy of morphine.

CONTEXT/OBJECTIVE: Spinal cord injury (SCI) is intensely life altering, affecting multiple body systems and functions, including the ability to walk. Exoskeleton assisted walking (EAW) is a rehabilitation tool that aims to support locomotor training, yet little is known about the patient experience. The purpose of this qualitative study, part of a prospective observational case series, was to increase our understanding of SCI patient experience using a robotic exoskeleton in this acute post-injury period. DESIGN: A qualitative descriptive approach was implemented in this study, with the aim to explore and understand participants’ experience with EAW training. PARTICIPANTS/SETTING: Nine of the 11 participants enrolled in the observational study agreed to participate in an interview. All participants had suffered a SCI, and had received their trauma care and inpatient rehabilitation at a tertiary center in Calgary, Alberta, Canada. RESULTS: The benefits to EAW use described by participants were primarily psychological and included the joy of eye level contact, excitement at being able to walk with assistance, improvement in mood, and hope for the future. Potential physiological benefits include increased strength, decreased spasticity and reduced pain. Challenges to EAW use include weakness and fatigue, and a fear of incontinence. CONCLUSION: Qualitative research will continue to be an important component in future research on the use of EAW training as part of the rehabilitation process. Increasing understanding of the participants experience with this novel therapeutic modality and technology will be fundamental to improve its implementation in clinical practice.

CONTEXT: Considering that SCI is the main cause of neurogenic bladder, in Brazil, studies and statistical data on the number of people with neurogenic bladder are practically non-existent. To ascertain the prevalence of neurogenic bladder among users of SARAH Network hospitals with traumatic and non-traumatic spinal cord injury. METHODS: Data collection form from electronic medical records to characterize the sample. The variables were related to sociodemographic data such as age, care unit, and date of admission; and to clinical data, such as main diagnosis, neurogenic bladder diagnosis. In the cases of traumatic spinal cord injury, the ASIA Impairment Scale (AIS) was considered. The statistical tests were Mann–Whitney, for two independent samples, and Pearson's Chi-squared, for the categorical variables. FINDINGS: The sample included 954 participants. The prevalence of neurogenic bladder was 94.65%, of which 67% had a traumatic spinal cord injury diagnosis and 69.32% were male. Mean age of the participants was 46.12 years old (SD = 15.78 years). CONCLUSION/CLINICAL RELEVANCE: The prevalence of neurogenic bladder found in the sample was 94.65%. The analysis showed that participants with TSCI are more afflicted by lower urinary tract dysfunction than those with NTSCI. TSCI was more prevalent among males and NTSCI was more prevalent among females. This was a pioneering study on the prevalence of neurogenic bladder in SCI in Brazil. However, further studies will be necessary to corroborate the data found here. The development of a database with national data is indispensable to obtain more reliable results that could provide a basis for public healthcare policies for the prevention and rehabilitation of people with SCI in Brazil.

Purpose Inflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs. Methods Mice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na. Results Our data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents. Conclusion These results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs., Graphical Abstract

BACKGROUND In cancer research, studying the quality of life trajectory helps us understand the complaints but also the cognitive, physical, and emotional aspects that can evolve positively. Examining both the suffering and the improvements expressed by the patients facilitates their care and their recovery knowing that an optimistic perception of the future is important for adaptative functioning after cancer. Through retrospective, present and prospective measures, we sought to characterize the subjective trajectory perceived by women with breast cancer about their cognitive, emotional and physical states, as it relates to quality of life. METHODS Nine hundred ninety women survivors of breast cancer (after curative treatments) described, on the appropriate scales, their perceived cognitive, emotional and physical states over three periods of time: from past care (i.e., retrospective analysis) to the future (i.e., projective analysis), including the present period, as a function of their treatment (chemotherapy vs. no chemotherapy) and surgery (lumpectomy vs. mastectomy) using ANCOVA. RESULTS The 732 women who had received chemotherapy perceived the most significant consequences, regardless of the type of surgery (η2= .01). Moreover, all survivors expressed an optimistic perception of the change in their states in the anticipated future as a normative optimistic perception. CONCLUSIONS Results are discussed in terms of the benefits of specific and early interventions that enable patients to cope better with the disease and its treatments by taking into account their more or less optimistic perception of the future.

Purpose Describe presumed microbial keratitis cases resulting in evisceration/enucleation from 2012 to 2016 in Sydney, Australia. Methods A retrospective case review included 33 patients. Cases were identified from pathology and hospital coding data. Sociodemographic and clinical details were collated. Results Mean age was 79 years (range: 38-100 years), and 64% female. There were 30 eviscerations and 3 enucleations, at a median time of 8 days (range: 1-270 days) due to endophthalmitis (n = 15, 45%). Major ocular associated factors included topical corticosteroid use in 12 patients (36%), exposure keratopathy in 4 (12%), ectropion in 3 (9%), degenerative corneal disease in 3 (9%), and corneal graft in 2 (6%). Pseudomonas aeruginosa was the most common isolate with no reports of antimicrobial resistance. Conclusions Educating elderly patients with a history of topical corticosteroid use, corneal or ocular surface disease about prompt hospital presentation and treatment of microbial keratitis may decrease the probability of losing the eye.

Yi Lin,1 Kaushik Chattopadhyay,2 Xi Yang,3 Jia-Lin Li,4 Yan-Shu Chen,4 Ye Zhou,4 Li Li4 1Center for Health Economics, Faculty of Humanities and Social Sciences, University of Nottingham, Ningbo, Zhejiang Province, People’s Republic of China; 2Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; 3Department of Nutrition, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 4Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of ChinaCorrespondence: Li LiDepartment of Endocrinology and Metabolism, Ningbo First Hospital, 59, Liuting Street, Ningbo, 315010, Zhejiang Province, People’s Republic of ChinaTel +86 13757426626Email lilyningbo@163.comYi LinCenter for Health Economics, Faculty of Humanities and Social Sciences, University of Nottingham, 199, Taikang East Road, University Park, Ningbo, 315100, People’s Republic of ChinaTel +86-13916608572Email Lily.Lin@nottingham.edu.cnPurpose: Type 2 diabetes (T2D) is one of the major public health concerns in China. Studies on the association between dietary salt intake and the glycemic response of T2D are lacking in China. The aim was to investigate the association between the levels of dietary salt intake and the plasma glucose, insulin and hemoglobin A1c (HbA1c) levels in T2D patients.Methods: Patients with T2D, who accepted management and treatment by the National Standardized Metabolic Disease Management Center at Ningbo First Hospital from March 2018 to January 2020, were included in this study. Dietary salt intake was assessed through a standardized food frequency questionnaire. Anthropometry, blood pressure and biomarkers were measured by well-trained endocrinology nurses. Generalized linear models (GLMs) were used to examine the associations.Results: A total of 1145 eligible T2D patients with a mean age of 51.4 years were included in the study. Fasting plasma glucose (FPG), 2-hour postprandial plasma glucose and 2-hour postprandial insulin were significantly increased across dietary salt categories. The GLMs further showed that dietary salt intake > 8 g/day was positively associated with FPG and HbA1c.Conclusion: Higher daily salt intake was found to be associated with FPG and HbA1c in T2D patients. Lifestyle education and promotion of salt reduction should be provided to T2D patients.Keywords: dietary salt, type 2 diabetes, blood glucose, insulin, glycated hemoglobin A1c, China

Arturas Kalniunas,1 Ipsita Chakrabarti,1 Rakhee Mandalia,1 Jasna Munjiza,2,3 Sofia Pappa1,2 1West London NHS Trust, London, UK; 2Division of Psychiatry, Imperial College London, London, UK; 3Central and North West London NHS Foundation Trust, London, UKCorrespondence: Sofia PappaRecovery Team East, Avenue House, 43-47 Avenue Road, London, W3 8NJ, UKEmail sofia.pappa@westlondon.nhs.uk; s.pappa@imperial.ac.ukObjective: We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area.Methods: Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting.Results: Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies.Conclusion: The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.Keywords: antipsychotic medication, akathisia, restlessness, suicidal behaviour

Thanya Limapichat, Krittapat Pattanapong Department of Emergency Medicine, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandCorrespondence: Thanya LimapichatDepartment of Emergency Medicine, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, ThailandTel +66 74-451705Fax +66 74-451704Email thanya_nl@yahoo.comObjective: To compare the effect of isotonic crystalloid solutions between lactated Ringer’s solution (LRS) and normal saline solution (NSS) on lactate clearance in septic patients at the emergency department (ED).Materials and Methods: This study is a single-center retrospective chart review. The study enrolled patients older than 18 years with sepsis and initial serum lactate level > 2 mg/dL in the ED. The primary outcome was to determine which isotonic solution was better for serum lactate clearance in septic patients. The secondary outcomes were serum creatinine change within 24 h and the 48-h survival rate after admission.Results: A total of 120 patients were enrolled with a median crystalloid volume administered in the ED of 1000 mL. Within 2 h of resuscitation, there was no difference in lactate clearance between the LRS and NSS groups with median values of 29.2% and 25%, respectively (P=0.839). The 48-h survival rate after admission did not differ between the LRS and NSS groups with median values of 90% and 86%, respectively. Both isotonic solutions increased serum creatinine levels within 24 h of treatment with median values of 0.3 for each group (P=0.647).Conclusion: Among septic patients in the ED treated with NSS or LRS, there was no difference in lactate clearance, serum creatinine change within 24 h, or 48-h survival. However, several factors were associated with increased lactate levels, such as older age and use of vasopressors and immunosuppressive agents.Keywords: lactate clearance, balance crystalloid, sepsis, NEWS

The authors' aim is to provide breast surgeons' perspectives on the relative importance of the criteria for choosing an appropriate surgery method between mastectomy (total removal of a breast) and breast-conserving surgery (removal of a breast cancer tumor and some of the normal tissue that surrounds it) for women with breast cancer by using the multicriteria decision-making method (MCDM). The Analytic Hierarchy Process (AHP), the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), and Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) methods are utilized. A decision hierarchy is set with a goal, criteria, and alternatives. We developed our model based on three main criteria, tumor-related, patient-related, and post-operative process-related factors and nineteen sub-criteria, as well as two alternatives, mastectomy and breast-conserving surgery (BCS). An online questionnaire was sent to the breast surgeons; we showed that the most important criteria are post-operative process-related factors, especially the demand for esthetic appearance based on 39 breast surgeons. Conversely, the least significant criteria are tumor-related factors. Furthermore, breast-conserving surgery is selected as the most appropriate surgery method for breast cancer patients using the AHP, TOPSIS, and VIKOR.

Crisis intervention teams in Berlin, Germany use a form of dialogic practice - a therapeutic approach based on the relational meaning of language - to develop an alternative means of negotiating risk and evaluating "outcome" in psychiatric experience. These clinicians bring familial networks into the process of crisis management, revealing meaningful "outcomes" regarding crisis care to be tethered to local concepts of chronicity and responsibility. To conceive of outcome in this context requires attention beyond the individual, and instead the consideration of a distributed outcome, in which living with risk, and its consequences, is bound to the collective experience of the network.

Vascular access for hemodialysis is of paramount importance. Although studies have found that central venous catheter (CVC) is often associated with poor outcomes and switching to arteriovenous fis...

Objective Method Results Conclusions Due to the COVID pandemic psychologists have been required to rapidly adapt to a different type of service delivery to ensure safety of the public and maintain the provision of essential psychological services within schools. In response, telehealth or online counselling became the norm across much of Australia. Psychologists in school settings were required to move many traditional face-to-face psychological services online to continue to support the needs of school communities. This project aimed to identify changes made to the practice of school psychology during COVID, the efficacy of these changes and potential applications within the field post COVID.Registered psychologists working in school settings across Australia were invited to participate in an online survey. Fifty-six participants completed questions related to their school psychological practice during COVID, they also completed the Counsellor’s Crisis Self Efficacy Scale, rating their level of confidence to respond in a crisis.Results identified a range of technology-informed changes to practice during COVID including greater use of telehealth in provision of service to clients, parents and schools. Respondents reported moderate to high levels of self-efficacy overall in their ability to respond during the crisis, and significant differences according to level of experience were identified.Respondents identified potential post COVID changes to practice that represented greater flexibility in modes of service delivery. Key Points What is already known about this topic: (1) Impact of COVID-19 on school psychological practice. (2) Benefits of telehealth. (3) Influences on crisis intervention self-efficacy. (1) Impact of COVID-19 on school psychological practice.(2) Benefits of telehealth.(3) Influences on crisis intervention self-efficacy. What this study adds: (1)Technology enabling factors to school psychological practice. (2)Relationship between crisis intervention self-efficacy and experience. (3)Opportunities to change model of service delivery. (1)Technology enabling factors to school psychological practice.(2)Relationship between crisis intervention self-efficacy and experience.(3)Opportunities to change model of service delivery. [ FROM AUTHOR] Copyright of Australian Psychologist is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The aim of the study was to investigate the influence of chitosan oligosaccharide (COS) on some antioxidant and cytokine levels in the rat hippocampus as well as synaptophysin (SYP) immunoreactivity in the cerebral cortex of the cadmium (Cd) exposed rats. Thirty-two male albino Wistar rats were divided randomly into four equal groups as control (C; n = 8), Cd (n = 8), COS (n = 8), and Cd + COS (CdCOS; n = 8). The rats in the Cd and CdCOS groups received Cd chloride (CdCl2) (2 mg/kg/d) orally by gastric gavage three times a week for 4 weeks. Besides, COS (200 mg/kg/d) was administered to COS and CdCOS groups five times a week for 4 weeks. Then, they were decapitated and hippocampal/cerebral cortex tissue samples were taken for measurement of GSH levels, CAT and SOD activities, MDA values, TNF-α, IL-6, and IL-10 levels as well as SYP immunoreactivity. Although tissue GSH levels were determined the lowest in the Cd group, these values were attenuated with COS treatment in the CdCOS group (p

Objective：Macrophages are the main source of inflammatory mediators and play important roles in the pathogenesis of rheumatoid arthritis (RA). Interleukin-21 (IL-21) regulates both innate and adaptive immune responses and exerts major effects on inflammatory responses that promote the development of RA. However, its effect on macrophage polarisation remains unclear.Methods：CD14+ monocytes of the peripheral blood of Human healthy donors (HD) and RA, and macrophages of RA synovial fluid (RA-SF MΦs) were isolated. IL-21 receptor (IL-21R) was detected by flow cytometry. Cytokine production by MΦs from different sources pre-treated with IL-21 and/or LPS was measured by real-time polymerase chain reaction (RT-PCR) and ELISA. CD14+ monocytes were differentiated into M1-like and M2-like macrophages via stimulation with GM-CSF, interferon-γ (IFN-γ), and LPS or M-CSF, IL-4, and IL-13, respectively. To determine the effect of IL-21 on macrophage polarisation, macrophage phenotypes, gene expression, and cytokine secretion were detected by flow cytometry, RT-PCR, and ELISA. TLR4 and ERK1/2 were determined by western blotting.Results：IL-21 exerted different effects on LPS-mediated inflammatory responses in various derived MΦs, and inhibited macrophages polarisation to M1-like macrophages and promote their polarisation to M2-like macrophages in HD and RA. Moreover, IL-21 inhibited LPS-mediated secretion of inflammatory cytokines, probably by downregulating the ERK1/2, in RA-SF MΦs.Conclusion：For the first time, we indicated that IL-21 inhibits LPS-mediated cytokine production in RA-SF MΦs, and impairs pro-inflammatory activity of M1-like macrophages, hereby exerting anti-inflammatory effects on RA. Thus, IL-21 might not be an appropriate therapeutic target for RA.

BACKGROUND Norway reports the highest prevalence of hip fractures in the world. Physiotherapists play a key-role in rehabilitation. PURPOSE To explore physiotherapists' experiences with rehabilitation trajectories of older adults after hip fracture across levels of care in Norway. METHODS A case-study design combined interviews and group-discussions with 22 physiotherapists in four hospitals and 12 primary health care settings in urban and rural municipalities in 2016 and 2018. A thematic content analysis was applied. RESULTS The physiotherapists viewed the rehabilitation trajectory after hip fracture as fragmented and poorly suited for patients with complex needs. Early hospital discharge, multiple transfers and insufficient staffing, put patients at risk of not receiving adequate services. Most at risk were patients with cognitive impairment. The physiotherapists' role and influence during the patients' rehabilitation course varied, depending on the health-care level. They viewed that current reforms and structural conditions limited the quality of geriatric care and the prioritization of patients with dementia, who risked getting no rehabilitation at all. CONCLUSION An orthogeriatric, person-centered approach to rehabilitation after hip fracture seems beneficial. A focus on cognitive impairment is needed requiring investment and professional skills' development. Political, economic, and organizational interventions should secure that, geriatric patients receive necessary rehabilitation services.

PURPOSE There is a lack of high-quality evidence about the effects of exercise or physical activity interventions for adults with lower limb amputations (LLAs). A planning meeting involving stakeholders (i.e., people with LLA, community advocates, health care providers, researchers) was organized to identify key research priorities related to exercise and physical activity for people with LLAs. METHODS We used a collaborative prioritized planning process with a pre-meeting survey and 2-day virtual meeting that included: identification and prioritization of challenges or gaps; identification and consolidation of solutions; and action planning. This process integrated a modified Delphi approach, including anonymous feedback in two surveys. RESULTS Thirty-five stakeholders participated. Six challenges related to exercise and physical activity for people with LLA were prioritized. One solution was prioritized for each challenge. After consolidation of solutions, participants developed five research action plans for research including: developing an on-line interface; developing and evaluating peer-support programs to support physical activity; examining integration of people with LLA into cardiac rehabilitation; development and evaluation of health provider education; and determining priority outcomes related to physical activity and exercise. CONCLUSIONS This collaborative process resulted in an action plan for amputation research and fostered collaborations to move identified priorities into action.IMPLICATIONS FOR REHABILITATIONLower limb amputations impact mobility leading to lower levels of physical activity.There are research gaps in our understanding of the effects of exercise or physical activity interventions for adults with lower limb amputations.Through a collaborative planning process, participants prioritized research directions on physical activity and exercise for people with LLA to advance research in the field.Action plans for research focused on developing online resources, peer support, cardiac rehabilitation for people with LLA, health provider education and determining priority outcomes related to physical activity and exercise.

PURPOSE Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown. MATERIALS AND METHODS We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalaemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage. RESULTS The patient required gradual escalation of antihypertensive medication to four drugs. During the diagnostic process we identified primary aldosteronism, cobalamin deficiency, severe obstructive sleep apnoea, and low baroreflex sensitivity (1.63 ms/mmHg). Following unilateral adrenalectomy, cobalamin supplementation and continuous positive airway pressure, we observed a spectacular improvement in the patient's blood pressure control, baroreflex sensitivity (4.82 ms/mmHg) and quality of life. CONCLUSIONS We report an unusual case of both masked arterial hypertension and primary aldosteronism. Elevated blood pressure values were masked in home and office measurements by coexisting hypotension which resulted most probably from deteriorated baroreflex sensitivity. Baroreflex sensitivity increased following treatment, including unilateral adrenalectomy. Hypertension can be masked by coexisting baroreceptor dysfunction which may derive from structural but also functional reversible changes.

International audience; Most lipids in our diet come under the form of triacylglycerols that are often redispersed and stabilized by surfactants in processed foods. In plant however, lipid assemblies constitute interesting sources of natural bioactive and functional ingredients. In most photosynthetic sources, polar lipids rich in ω3 fatty acids are concentrated. The objective of this review is to summarize all the knowledge about the physico-chemical composition, digestive behavior and oxidative stability of plant polar lipid assemblies to emphasize their potential as functional ingredients in human diet and their potentialities to substitute artificial surfactants/antioxidants. The specific composition of plant membrane assemblies is detailed, including plasma membranes, oil bodies, and chloroplast; emphasizing its concentration in phospholipids, galactolipids, peculiar proteins, and phenolic compounds. These molecular species are hydrolyzed by specific digestive enzymes in the human gastrointestinal tract and reduced the hydrolysis of triacylglycerols and their subsequent absorption. Galactolipids specifically can activate ileal break and intrinsically present an antioxidant (AO) activity and metal chelating activity. In addition, their natural association with phenolic compounds and their physical state (Lα state of digalactosyldiacylglycerols) in membrane assemblies can enhance their stability to oxidation. All these elements make plant membrane molecules and assemblies very promising components with a wide range of potential applications to vectorize ω3 polyunsaturated fatty acids, and equilibrate human diet.

A proper junction of the prosthesis and the abdominal wall is important in successful hernia repair. The number of tacks should be balanced to assure appropriate mesh fixation and not to induce post-operative pain. Numerical simulations help to find this balance. The study is aimed at creating a proper numerical model of a knitted surgical mesh subjected to boundary conditions and load occurring in the abdominal cavity. Continuous, anisotropic constitutive relation is considered to reflect the mesh behaviour. Different sets of material law parameters are determined on the basis of different bi-axial tests setups. Force- and displacement-controlled tests with different ratios are considered. Consequently, some numerical model variants are obtained featuring various reaction distributions in the scaffold fixation points. The proper variant is selected based on comparison of the position of maximal reaction force in the numerical model and in the reference physical model of operated hernia. Force-driven tests have shown anisotropic mesh behaviour, while equibiaxial displacement-driven test has demonstrated reduced anisotropic response. Within seven scenarios of constitutive parameters identification (based on single or combined experimental data), the equibiaxial force-controlled test appeared to produce the most relevant model to follow the prosthesis behaviour under pressure. The position of maximal reaction force in such model is similar to obtained in the physical hernia model. The equibiaxial force-driven test provides most suitable data for Gasser-Ogden-Holzapfel constitutive model identification of a considered surgical mesh to be used to model the mesh under pressure.

Zilpaterol and clenbuterol are two β-adrenergic agonist drugs used in animal production. Both drugs have anabolic effects with advantages on carcass yield. Meanwhile, zilpaterol is approved for animal feed in authorized countries. Clenbuterol is a banned substance due to the risk of toxicity; however, it is still being used in unknown dose levels in many farm species. Therefore, the use and abuse of these substances should be closely monitored, considering the clenbuterol ability and the not proved yet of zilpaterol to produce reactive oxygen and nitrogen species. Regarding glutathione which is the main intracellular antioxidant plays detoxification functions on liver metabolism; in this work, it is our interest to know the capacity of chitosan-glutathione nanoparticles (CS/GSH-NP) as a complementary source of exogenous GSH to modify the oxide-reduction status on bovine precision-cut liver slice cultures (PCLS) exposed to clenbuterol and zilpaterol. A single drug assay was performed in first instance by adding clenbuterol, zilpaterol, chitosan nanoparticles (CS-NP), and CS/GSH-NP. Then combinate drug assay was carried out by testing clenbuterol and zilpaterol combined with CS-NP or CS/GSH-NP. The results showed that both β-adrenergic agonists modify in a dose-dependent manner in oxide-reduction response through ROS generation. The activity or content of glutathione peroxidase activity, intracellular GSH, gamma glutamyl-transpeptidase, aspartate aminotrasnferase and alanine aminotrasnferase were modified. The exogenous GSH delivered by nanoparticles could be used to modulate these markers.

BACKGROUND AND AIMS Endoscopic stent placement is a palliative therapy for malignant digestive tract obstruction. However, its use for malignant afferent loop obstruction (mALO) has not been adequately investigated. METHODS From March 2009 to December 2020, 137 patients with mALO who underwent endoscopic stent placement at three tertiary care centers were retrospectively enrolled. The primary aim of this study was to compare stent dysfunction (SD) between the covered self-expandable metal stent (CSEMS) and uncovered self-expandable metal stent (UCSEMS) groups, with subgroup analysis among patients with extrinsic and intrinsic tumors separately. RESULTS Twenty-three patients developed SD in the CSEMS group and 29 patients in the UCSEMS group (log-rank p = .974). The primary contributors to SD included a higher risk of stent migration in the CSEMS group and stent ingrowth in the UCSEMS group (p = .003; p

To determine associations between frailty and patient outcomes for participants in an acute rehabilitation program.Retrospective participant data (n = 987) was extracted, and correlations between t...

PURPOSE To analyze the agreement of the predicted intraocular lens (IOL) power obtained with ANTERION, IOLMaster 700 and Pentacam AXL biometers. METHODS We calculated the monofocal and trifocal IOL power using the SRK/T, Haigis, Barrett Universal II and Hoffer Q formulas for 106 eyes. IOL power agreement between devices was evaluated using the Bland-Altman method. RESULTS We found significant differences between biometers comparisons (p 0.05), with the same outcomes for medium- and long-eyes. No significant differences were found using the SRK/T, Haigis, or Hoffer Q formulas for short-eyes (p > 0.1). However, Barrett Universal II formula produced significant differences (p

INTRODUCTION Physical exercise appeared to be effective, when implemented as an adjuvant to the pharmacotherapy option, in a variety of painful conditions. Peripheral neuropathic pain (PNP) is very prevalent and affects up to two-thirds of individuals with polyneuropathy (PN), regardless of etiology. The aim of this systematic review was to evaluate the currently available studies that assess adjuvant physical exercise for the management of PNP. METHODS A systematic literature search was conducted in the PubMed international database. For the systematic search, three medical subject headings (MeSH) were used. Term A was 'physical exercise' OR 'exercise' OR 'activity' OR 'workout' OR 'training'; term B was 'pain' OR 'painful'; term C was 'neuropathy' OR 'polyneuropathy.' Additionally, three filters were used: human subjects, English language, and full text. The reference lists of eligible papers and relevant reviews were also meticulously searched in order to include further relevant studies. Six papers eligible to be included were identified. RESULTS Physical exercise in various forms can be of benefit in the management of PNP when used as an adjuvant to the standard care. Overall, using the American Society of Interventional Pain Physicians (ASIPP) criteria, the current best available evidence exists for both aerobic and muscle strengthening exercise programs (level II evidence). The intensity of the exercise seems to play a significant role, with higher intensity interval training programs being more promising, though this remains to be confirmed in future studies. CONCLUSIONS Physical exercise is a promising non-pharmacological intervention for the management of PNP. Future RCTs should be conducted to make a face-to-face comparison of the available exercise treatments with the aim to design specific exercise programs for patients with PNP.