The median SDM knowledge scores for people who had discussed ACP (3.0 vs 2.0, U=1 45 222, z=6.910, p<0.001), documented their ACP preferences (3.0 vs 2.0, U=71 984, z=4.087, p<0.001) or acted in the SDM role (3.0 vs 2.0, U=56 353, z=-3.694, p<0.001) were significantly higher compared with those who had not.

The Australian public may have low to moderate knowledge about the SDM role and access only minimal support when making challenging medical decisions.

The Australian public may have low to moderate knowledge about the SDM role and access only minimal support when making challenging medical decisions.

Opioids may impair the ability to drive safely, particularly when first prescribed or with dose titration. We investigated whether clinicians evaluate driving status and provide opioid-related driving advice when initiating opioids among people with advanced lung cancer.

A retrospective medical record review of outpatients with advanced non-small cell lung cancer seen at an Australian tertiary referral centre between 1 January 2015 and 31 December 2019 was undertaken to determine frequency of opioid prescription and documentation of driving status and education regarding driving safety while taking opioids.

Of 1022 patients screened, 205 were commenced on opioid therapy. Forty-seven (23%) patients had driving status documented. According to medical records, education about driving safety while on opioids was provided to two (1%) patients on opioid initiation. Ten (5%) patients received opioid-related driving education at least once at follow-up appointments. The content of the education was infrequently documented, and when documented, focused on opioid side effects impacting driving. Opioid doses were often escalated at follow-up appointments.

According to documentation in medical records, clinicians infrequently assessed driving status on opioid initiation and rarely provided education regarding opioid-related driving risks. Further research and clearer guidance regarding opioids and driving safety in the cancer population are required.

According to documentation in medical records, clinicians infrequently assessed driving status on opioid initiation and rarely provided education regarding opioid-related driving risks. Further research and clearer guidance regarding opioids and driving safety in the cancer population are required.

Fibrotic strictures in the gastrointestinal tract are frequent in Crohn’s disease. Endoscopic dilation is a standard treatment. However, recurrence is common after dilation and there are complications such as bleeding or perforation. Endoscopic treatment using self-expandable metal stents has shown diverging results. The aim of this study was to evaluate the outcome of endoscopic treatment with a self-expandable stent in ileocecal Crohn’s disease.

Patients with Crohn’s disease and a symptomatic ileocecal stricture were eligible for prospective, consecutive inclusion in a single-centre setting. Patients were randomised to treatment with either 18 mm balloon dilatation (Group

) or stenting (Group

) using a 20 mm diameter, partially covered Hanarostent NCN. Patients were followed for a minimum of 24 months postendoscopy. Outcomes were technical success, adverse events and clinical success (defined as no need for repeated interventions).

Thirteen patients (Group

n=6; Group

=7) were included with twelve patients (Group

n=5; Group

=7) being eligible for complete follow-up. Technical success was achieved in all cases. Adverse events were border-line significantly more common in the Group

4/7 (57%) (pain n=3; pain and rectal bleeding n=1) compared with the Group

0/5 (0%), p=0.08, which resulted in preterm termination of the study. The clinical success rate was Group

6/7 (86%) vs Group

1/5 (20%), p=0.07.

Patients with strictures related to Crohn’s disease may benefit from treatment with self-expandable metal stents rather than dilatation. However, there seems to be an increased risk for patient pain after stenting, which has to be considered and handled.

The study was registered at Clinical Trials (NCT04718493).

The study was registered at Clinical Trials (NCT04718493).Inflammatory bowel diseases such as ulcerative colitis (UC) may be complicated by several extraintestinal manifestations. These involve joints, skin, eyes and less commonly lungs and heart. Myocarditis may result from the toxic effect of drugs (ie, mesalazine) commonly used for the treatment of UC or due to infections (eg, Coxsackieviruses, enteroviruses, adenovirus). Here, we report a case of a 26-year old man affected by UC and complicated by two episodes of myocarditis. Both episodes occurred during two severe exacerbations of UC. However, in both cases the aetiology of myocarditis remains uncertain being ascribable to extraintestinal manifestation, drug toxicity or both.Understanding energy use is central to understanding an animal’s physiological and behavioural ecology. However, directly measuring energy expenditure in free-ranging animals is inherently difficult. The doubly labelled water (DLW) method is widely used to investigate energy expenditure in a range of taxa. Although reliable, DLW data collection and analysis is both financially costly and time consuming. Dynamic body acceleration (e.g. VeDBA) calculated from animal-borne accelerometers has been used to determine behavioural patterns, and is increasingly being used as a proxy for energy expenditure. Still its performance as a proxy for energy expenditure in free-ranging animals is not well established and requires validation against established methods. In the present study, the relationship between VeDBA and the at-sea metabolic rate calculated from DLW was investigated in little penguins (Eudyptula minor) using three approaches. Both in a simple correlation and activity-specific approaches were shown to be good predictors of at-sea metabolic rate. The third approach using activity-specific energy expenditure values obtained from literature did not accurately calculate the energy expended by individuals. However, all three approaches were significantly strengthened by the addition of mean horizontal travel speed. These results provide validation for the use of accelerometry as a proxy for energy expenditure and show how energy expenditure may be influenced by both individual behaviour and environmental conditions.

To assess the accuracy of real-time telemedicine to diagnose and manage paediatric eye conditions.

Prospective, non-inferiority study analysing agreement in diagnoses and management plans between telemedicine and in-person examinations.

Paediatric ophthalmology clinic.

Children 0-17 years, English-speaking or Spanish-speaking, able to participate in age-appropriate manner, either previously seen by the optometrist and required ophthalmology referral or newly referred from outside source.

Paediatric optometrist conducted examinations using digital equipment and streamed live to a paediatric ophthalmologist who recorded diagnoses and management plans, then re-examined patients in-person. Subjects were masked to the fact they would see the ophthalmologist in-person, same-day.

Discrepancy in management plan or diagnosis between telemedicine and in-person examinations. Non-inferiority threshold was <1.5% for management plan or <15% for diagnosis discrepancies.

210 patients participated in n ophthalmologists and optometrists using this technology.Specific mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A, a hereditary syndrome characterized by tumorigenesis in multiple glandular elements. In rare instances, MEN2A-associated germline RET mutations have also occurred with non-MEN2A associated cancers. One such germline mutant RET mutation occurred concomitantly in a young adult diagnosed with alveolar rhabdomyosarcoma, a pediatric and young adult soft-tissue cancer with a generally poor prognosis. Although tumor tissue samples were initially unable to provide a viable cell culture for study, tumor tissues were sequenced for molecular characteristics. Through a hierarchical clustering approach, the index case sample was matched to several genetically similar cell models, which were transformed to express the same mutant RET as the index case and used to explore potential therapeutic options for mutant RET-bearing alveolar rhabdomyosarcoma. We also determined whether the RET mutation associated with the index case caused synthetic lethality to select clinical agents. From our investigation, we did not identify synthetic lethality associated with the expression of that patient’s RET variant, and overall we did not find experimental evidence for the role of RET in rhabdomyosarcoma progression.Immunotherapeutic manipulation of the antitumor immune response offers an attractive strategy to target genomic instability in cancer. A subset of tumor-specific somatic mutations can be translated into immunogenic and HLA-bound epitopes called neoantigens, which can induce the activation of helper and cytotoxic T lymphocytes. However, cancer immunoediting and immunosuppressive mechanisms often allow tumors to evade immune recognition. Recent evidence also suggests that the tumor neoantigen landscape extends beyond epitopes originating from nonsynonymous single-nucleotide variants in the coding exome. Here we review emerging approaches for identifying, prioritizing, and immunologically targeting personalized neoantigens using polyvalent cancer vaccines and T-cell receptor gene therapy. SIGNIFICANCE Several major challenges currently impede the clinical efficacy of neoantigen-directed immunotherapy, such as the relative infrequency of immunogenic neoantigens, suboptimal potency and priming of de novo tumor-specific T cells, and tumor cell-intrinsic and -extrinsic mechanisms of immune evasion. A deeper understanding of these biological barriers could help facilitate the development of effective and durable immunotherapy for any type of cancer, including immunologically „cold” tumors that are otherwise therapeutically resistant.

To review the effectiveness of travel measures implemented during the early stages of the COVID-19 pandemic to inform changes on how evidence is incorporated in the International Health Regulations (2005) (IHR).

We used an abbreviated Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols to identify studies that investigated the effectiveness of travel-related measures preprinted or published by 1 June 2020.

We identified 29 studies, of which 26 were modelled. Thirteen studies investigated international measures, while 17 investigated domestic measures (one investigated both). There was a high level of agreement that the adoption of travel measures led to important changes in the dynamics of the early phases of the COVID-19 pandemic the Wuhan measures reduced the number of cases exported internationally by 70%-80% and led to important reductions in transmission within Mainland China. Additional travel measures, including flight restrictions to and from China, may have led to additional reductions in the number of exported cases. Few studies investigated the effectiveness of measures implemented in other contexts. Early implementation was identified as a determinant of effectiveness. Most studies of international travel measures did not account for domestic travel measures thus likely leading to biased estimates.

Travel measures played an important role in shaping the early transmission dynamics of the COVID-19 pandemic. There is an urgent need to address important evidence gaps and also a need to review how evidence is incorporated in the IHR in the early phases of a novel infectious disease outbreak.

Travel measures played an important role in shaping the early transmission dynamics of the COVID-19 pandemic. There is an urgent need to address important evidence gaps and also a need to review how evidence is incorporated in the IHR in the early phases of a novel infectious disease outbreak.

To compare combined phacoemulsification plus endoscopic cyclophotocoagulation (ECP) versus phacoemulsification alone in primary angle-closure glaucoma (PACG) with coexisting cataract.

Prospective randomized controlled clinical trial-a pilot study.

Forty-eight PACG eyes of 48 patients with coexisting cataract.

Recruited patients were randomized into undergoing phacoemulsification plus ECP or phacoemulsification alone. After surgery, patients were followed up every 3 months for 2 years.

Intraocular pressure (IOP) and requirement for topical glaucoma drugs.

Twenty-seven PACG eyes were randomized to receive combined phacoemulsification plus ECP, and 21 PACG eyes underwent phacoemulsification alone. There was no statistically significant difference in mean preoperative IOP between combined phacoemulsification plus ECP and phacoemulsification groups (20.0 mmHg vs. 20.7 mmHg; P= 0.71). Phacoemulsification plus ECP resulted in lower mean postoperative IOP than phacoemulsification alone at all follow-up vihis pilot study, but the differences did not reach statistical significance at the majority of time points. A large-scale randomized controlled trial is in progress to evaluate these differences.

Combined phacoemulsification plus ECP is noninferior to phacoemulsification alone in controlling IOP in PACG eyes with cataract. Combined phacoemulsification plus ECP resulted in lower mean IOP and glaucoma drug requirement than phacoemulsification alone at all follow-up visits in this pilot study, but the differences did not reach statistical significance at the majority of time points. A large-scale randomized controlled trial is in progress to evaluate these differences.

In this study, we describe common demographic and clinical characteristics of the glaucoma patient population attending vision rehabilitation.

Cross-sectional study.

Patients attending a hospital-based vision rehabilitation center with a primary ocular diagnosis of glaucoma.

Participants’ charts were retrospectively reviewed. Data extracted from medical records included demographics, referring physician, ocular history, glaucoma diagnosis, past ocular surgery, intraocular pressure, optic nerve findings, results of a functional intake assessing activities of daily living, depression, visual hallucinations, best-corrected visual acuity (BCVA), mean deviation (MD) scores on visual field testing, and log contrast sensitivity (CS).

Participant demographic information, ocular history, self-reported difficulty with activities of daily living, depression, visual hallucinations, BCVA, visual field, and CS.

The mean age of patients in this study was 77 years and ranged from 8 to 103 years. Ninety percent ofover time.

Most glaucoma patients attending vision rehabilitation are not legally blind, but many are functionally monocular. This may cause greater difficulty performing functions that require the use of binocularity. Increasing the referral of younger glaucoma patients to vision rehabilitation may help patients learn to cope with the loss of visual function that occurs over time.Spinal cord injury (SCI) causes immune activation of resident macrophages/microglia. Activated macrophages/microglia have two different phenotypes, the pro-inflammatory classically activated (M1) phenotype and the anti-inflammatory alternatively activated (M2) phenotype. M1 phenotype macrophages/microglia are the key factor in inflammation. The treatment of SCI remains a huge challenge due to the nontargeting and inefficiency of anti-inflammatory drugs through the blood-brain barrier (BBB). The purpose of this experiment was to design M2-type primary peritoneal macrophages exosomes (Exos) as a drug carrier for berberine (Ber), which can be efficiently targeted to deliver drugs to the injured spinal cord due to the natural advantage of Exos across the BBB. The Exos with particle size of 125±12 nm were loaded with by an ultrasonic method and the drug loading reached 17.13 ±1.64%. The Ber release experiment showed that the loaded sample (Exos-Ber) exhibited sustained release effect, and the cumulative release amome more selective. However, due to the special microenvironment after central nervous system damage, some non-degradable inorganic materials will increase the pressure of self-healing and even secondary damage to neurons, which has been solved by the emergence of exosomes. Some previous studies used tumor cell line exosomes as drug carriers, but the carcinogenic factors carried by themselves have extremely high hidden dangers, and endogenous macrophage exosomes have absolute advantages over their safety.The immune system plays an essential role in tissue repair and regeneration. Regardless of innate or adaptive immune responses, immunosuppressive strategies such as macrophage polarization and regulatory T (Treg) cell induction can be used to modulate the immune system to promote tissue repair and regeneration. Biomaterials can improve the production of anti-inflammatory macrophages and Treg cells by providing physiochemical cues or delivering therapeutics such as cytokines, small molecules, microRNA, growth factors, or stem cells in the damaged tissues. Herein, we present an overview of immunosuppressive modulation by biomaterials in tissue regeneration and highlight the mechanisms of macrophage polarization and Treg cell induction. Overall, we foresee that future biomaterials for regenerative strategies will entail more interactions between biomaterials and the immune cells, and more mechanisms of immunosuppression related to T cell subsets remain to be discovered and applied to develop novel biomaterials for tissue repair and regeneration. STATEMENT OF SIGNIFICANCE Immunosuppression plays a key role in tissue repair and regeneration, and biomaterials can interact with the immune system through their biological properties and by providing physiochemical cues. Here, we summarize the studies on biomaterials that have been used for immunosuppression to facilitate tissue regeneration. In the first part of this review, we demonstrate the crucial role of macrophage polarization and induction of T regulatory (Treg) cells in immunosuppression. In the second part, distinct approaches used by biomaterials to induce immunosuppression are introduced, which show excellent performance in terms of promoting tissue regeneration.Depletion of human serum albumin (HSA), the most abundant protein in human plasma, from serum/plasma is a prerequisite before their proteomic analysis. Molecularly imprinted polymers (MIPs) using HSA as a template have been designed for this purpose, but suffer from a low sorption capacity and low selectivity. Here, a new HSA-imprinted polymer was synthesized using N-isopropylacrylamide (NIPAM) as the main monomer; acrylamide (AAm), methacrylic acid (MAA), and dimethylaminoethyl methacrylate (DMAEMA) as functional monomers; and oligoglutamic acid-based peptide crosslinker (PC) as a crosslinker at pH 5.5. When pH is adjusted to 7.4, the peptide chains in the polymer change from a helical conformation to an extended coil conformation, and the polymer swells. Consequently, the template protein is removed completely. When pH is adjusted back to 5.5, the peptide chains fold back precisely to the helical conformation. Both the size and shape of the imprint cavities are restored. Therefore, the polymer rebinds the tnted polymer (MIP) using human serum albumin (HSA) as a template was synthesized using N-isopropylacrylamide (NIPAM) as the main monomer; acrylamide (AAm), methacrylic acid (MAA), and dimethylaminoethyl methacrylate (DMAEMA) as functional monomers; and oligoglutamic acid-based peptide crosslinker as a crosslinker. Because of the reversible and precise pH-induced helix-coil transition of the peptide chains, the template protein was removed facilely and completely under mild conditions. Simultaneously, a significant improvement in imprinting efficiency was obtained. The sorption capacity was as high as 648.05 mg/g and the imprinting factor was 7.9. Because of its high selectivity and high binding capacity, the MIP synthesized here is highly promising for the depletion of HSA, the most abundant protein in serum, which is a prerequisite for its proteomic analysis. For the first time, complete and selective depletion of HSA from human serum was achieved using a protein-imprinted polymer.

Severe food allergic reactions can be life-threatening or fatal and are experienced by up to 40% of children with food allergies, with adolescents at greatest risk. There are no comprehensive measures to assess food allergy management behaviors that could prevent allergic reactions.

To describe food allergy self-management behaviors as reported by adolescents on a 24-hour recall measure and identify related factors.

Adolescents aged 10 to 14 years with immunoglobulin E-mediated food allergy completed the Food Allergy Management 24-Hour Recall as an interview. Participants answered questions on each food they ate on the previous day and food allergy self-management behaviors.

Participants were a diverse sample (28% White) of 101 adolescents (mean age=11.80 years; 53% male sex). Most meals and snacks (76%) were observed by adults. Epinephrine autoinjectors (EAIs) were reportedly available for almost all meals and snacks (93%). Almost all foods had been eaten before (95%) and were verified as allergen free (92%). Furthermore, 35% of the time, past experience with the food was the only method used to verify safety. Child age, number of food allergies, or time since allergic reaction was not related to self-management behavior. EAI availability and ingredient verification were most common at home and in school; adult observation was least likely in the home.

Adolescents reported that EAIs were frequently available, but they relied on past experience with food to determine safety. Appropriate assessment of food safety should be a primary intervention target. The Food Allergy Management 24-Hour Recall may be a useful tool to assess and track food allergy self-management.

Adolescents reported that EAIs were frequently available, but they relied on past experience with food to determine safety. Appropriate assessment of food safety should be a primary intervention target. The Food Allergy Management 24-Hour Recall may be a useful tool to assess and track food allergy self-management.

This study aimed to evaluate the accuracy of deformable image registration (DIR) algorithms using data sets with different levels of ground-truth deformation vector fields (DVFs) and to investigate the correlation between DVF errors and contour-based metrics.

Nine pairs of digital data sets were generated through contour-controlled deformations based on 3 anonymized patients’ CTs (head and neck, thorax/abdomen, and pelvis) with low, medium, and high deformation intensity for each site using the ImSimQA software. Image pairs and their associated contours were imported to MIM-Maestro, Raystation, and Velocity systems, followed by DIR and contour propagation. The system-generated DVF and propagated contours were compared with the ground-truth data. The correlation between DVF errors and contour-based metrics was evaluated using the Pearson correlation coefficient (r), while their correlation with volumes were calculated using Spearman correlation coefficient (rho).

The DVF errors increased with increasing pends on anatomic site, deformation intensity, organ size, and so forth. This study provides benchmark tables for evaluating DIR accuracy in various clinical scenarios.

Most contour-based metrics had no correlation with DVF errors. For adaptive radiation therapy, well-performed contour propagation does not directly indicate accurate dose deformation and summation/accumulation within each contour (determined by DVF accuracy). Tolerance values for DVF errors should vary as the acceptable accuracy for overall adaptive radiation therapy depends on anatomic site, deformation intensity, organ size, and so forth. This study provides benchmark tables for evaluating DIR accuracy in various clinical scenarios.

Low-dose-rate brachytherapy is a highly effective treatment modality for prostate carcinoma, but postimplant dosimetry quality is essential and correlated with likelihood of treatment success. Registered ultrasound and fluoroscopy (iRUF) can facilitate real-time intraoperative monitoring and plan adaptation, with the aim of attaining superior dosimetric outcomes. The purpose of this research was to compare clinical postimplant dosimetric results of iRUF-guided brachytherapy against brachytherapy using standard ultrasound-guided intraoperative dosimetry methods.

We analyzed postimplant dosimetry in 292 patients treated with Pd-103 between January 2007 and December 2018. All patients had postimplant dosimetry measured on day 0 to 1 using fused magnetic resonance/computed tomography assessment. Fifty-two patients were treated in 2 prospective clinical trials using iRUF intraoperative dosimetry, including 6 patients in a pilot study and 46 treated in a phase 2 study. Postimplant dosimetry in iRUF-treated patients was compared with dosimetry from 240 patients treated using standard (real-time ultrasound) intraoperative seed tracking.

For every parameter measuring dose coverage to the prostate, iRUF patients had significantly higher values, irrespective of adjustment for year of treatment. In adjusted analyses, parameters of dose to urethra and rectum were not significantly higher among iRUF-treated patients.

Use of iRUF intraoperative dosimetry was associated with improved postimplant dose coverage in prostate, without associated increases in doses to urethra or rectum.

Use of iRUF intraoperative dosimetry was associated with improved postimplant dose coverage in prostate, without associated increases in doses to urethra or rectum.

Symptomatic polycystic liver disease (PLD) with massive hepatomegaly represents a challenging surgical issue. In this work, we focused on early and long term outcomes after partial hepatectomy with cyst fenestration (PHCF) in selected patients.

All patients who had PHCF for treatment of PLD between January 2003 and December 2019 in our center were included in this study. PHCF was undertaken if at least one hepatic section was relatively spared from PLD, afferent and efferent hepatic vasculature was patent, and liver function was maintained.

Twenty nine patients (25 women) with a mean age of 54.6 ± 9 years underwent PHCF. Major hepatectomy was performed in all cases with 4.3 ± 0.8 resected segments. Overall perioperative morbidity (Clavien ≥ II) and mortality rates were 41.4.6% and 13.8% respectively. Significant postoperative liver volume reduction was 52.8% within the first year and 55.5% thereafter. From preoperative evaluation, performance status (PS) normalized or improved in 84% of patients. After a mean follow-up time of 70.8 ± 65 months, overall patient survival was 82.7%. In univariate analysis, PS, initial liver volume, operative time and transfusion were associated with post-operative complications and PS, preoperative cyst infection, portal hypertension, transfusion, postoperative sepsis and persistent ascites were associated with mortality.

Our study confirms that in spite of significant morbidity rate, PHCF allows a massive reduction of liver volume in selected patients with symptomatic PLD and is highly and durably effective for the reduction of liver volume and improvement of quality of life.

Our study confirms that in spite of significant morbidity rate, PHCF allows a massive reduction of liver volume in selected patients with symptomatic PLD and is highly and durably effective for the reduction of liver volume and improvement of quality of life.

Currently, there is no pharmacotherapy for non-alcoholic steatohepatitis (NASH), a common liver disorder. In contrast, primary biliary cholangitis (PBC) is a chronic cholestatic liver disease for which ursodeoxycholic acid (UDCA) is the drug of choice. However, 50% of PBC patients may not respond to UDCA. Obeticholic acid (OCA) is emerging as a vital pharmacotherapy for these chronic disorders. We aimed to analyse the safety and efficacy of OCA.

We performed an extensive search of electronic databases from 01/01/2000 to 31/03/2020. We included randomized controlled trials of OCA in patients with NASH, PBC, and primary sclerosing cholangitis (PSC). We assessed the histological improvement in NASH, reduction in alkaline phosphatase (≤1.67 ULN) in PBC, and the adverse effects of OCA.

Seven RCTs (n = 2834) were included. Of the total RCTs, there were three on both NASH and PBC and one on PSC. OCA improved NASH fibrosis [OR 1.95 (1.47-2.59; p < 0.001)]. With the 10 mg OCA dose, the odds of improvement was 1.61 (1.03-2.51; p = 0.03), while with the 25 mg dose, it was 2.23 (1.55-3.18; p < 0.001). However, 25 mg OCA led to significant adverse events and discontinuation of the drug [2.8 (1.42-3.02); p < 0.001)] compared with 10 mg OCA [0.95 (0.6-1.5); p = 0.84] in NASH patients. In PBC patients, the response to 5 mg OCA was better than with the higher doses [5 mg 7.66 (3.12-18.81; p < 0.001), 10 mg 5.18 (2-13.41; p = 0.001), 25 mg 2.36 (0.94-5.93; p = 0.06), 50 mg 4.08 (1.05-15.78; p = 0.04)]. The risk of pruritus was lowest with 5 mg OCA.

Lower doses of OCA are effective and safe in NASH and cholestatic liver disease. While 10 mg OCA is effective for NASH fibrosis regression, only 5 mg OCA is required for PBC.

Lower doses of OCA are effective and safe in NASH and cholestatic liver disease. While 10 mg OCA is effective for NASH fibrosis regression, only 5 mg OCA is required for PBC.

Circular RNAs (circRNAs) contain a new class of non-coding RNAs that play an important role in adjusting biological function and gene expression. But the function of circRNAs in gastric cancer remains unclear. In the present research, we explored the functions of circular RNA AFF2(circAFF2, hsa_circ_0001947) in gastric cancer cells and an animal model of gastric cancer.

The expression of circAFF2, microRNA-6894-5p (miR-6894-5p), and Anthrax toxin receptor 1 (ANTXR 1) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell counting kit 8 (CCK-8) and transwell assays were used to analyze the knockdown effects of circAFF2, miR-6894-5p, and overexpression of ANTXR 1 on cell proliferation, migration, and invasion abilities. Binding interactions between, circAFF2 and miR-6894-5p and between, miR-6894-5p and ANTXR 1 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in nude mice.

The result showed that circAFF2 expression was significantly increased in gastric cancer cell lines and tissues. The knockdown of circAFF2 dramatically suppressed the cell migration, invasion and proliferation of gastric cancer cells. In vivo studies showed that knockdown of circAFF2 delayed tumor growth. Furthermore, we revealed that circAFF2 functioned as a sponge to absorb miR-6984-5p and elevated the expression of ANTXR 1.

CircAFF2 acts as an oncogene in gastric cancer and exerts its effects via miR-6894-5p/ANTXR 1 signaling.

CircAFF2 acts as an oncogene in gastric cancer and exerts its effects via miR-6894-5p/ANTXR 1 signaling.

An esophageal hypervigilance and anxiety scale (EHAS) was developed in English to assess the psychological process in patients with esophageal disorders. The aim of the current study was to validate this scale in French.

Patients referred for esophageal high resolution manometry (HRM) were offered to fill out different questionnaires including EHAS, Eckart score and gastro-esophageal reflux disease-questionnaire (GERDQ) score. EHAS was translated in French by 2 French native speaker experts in esophageal motility. Patients were grouped according to the indications of HRM (dysphagia, reflux, other). The total EHAS score was calculated and compared between groups. The validation method used the assessment of internal consistency with Cronbach’s α and reliability with Guttman split-half reliability.

Among the 607 patients who accepted to fill out questionnaires, the EHAS questionnaire was completed and analyzable in 469 patients. The total score had an excellent internal consistency (Cronbach’s α = 0.91) and reliability (Guttman statistic = 0.86). EHAS score was not different between groups while Eckardt score was logically higher in patients with dysphagia than in others (p < 0.001) and GERDQ score was higher in patients with reflux than in those with dysphagia (p < 0.001). Despite different load on anxiety and hypervigilance scales, inter-item correlations and average scores did not differ between the original and the French EHAS.

EHAS is a valid questionnaire in French. It can be interpreted using the original EHAS score. Further studies are required to demonstrate the utility of this score in patients’ management.

EHAS is a valid questionnaire in French. It can be interpreted using the original EHAS score. Further studies are required to demonstrate the utility of this score in patients’ management.The peroxisome proliferator activated receptor gamma (PPARG) nuclear receptor regulates energy metabolism and insulin sensitivity. In this study, we present novel evidence for an essential role of PPARG in the regulation of osteocyte function, and support for the emerging concept of the conjunction between regulation of energy metabolism and bone mass. We report that PPARG is essential for sclerostin production, a recently approved target to treat osteoporosis. Our mouse model of osteocyte-specific PPARG deletion (Dmp1CrePparγflfl or γOTKO) is characterized with increased bone mass and reduced bone marrow adiposity, which is consistent with upregulation of WNT signaling and increased bone forming activity of endosteal osteoblasts. An analysis of osteocytes derived from γOTKO and control mice showed an excellent correlation between PPARG and SOST/sclerostin at the transcript and protein levels. The 8 kb sequence upstream of Sost gene transcription start site possesses multiple PPARG binding elements (PPREs) with at least two of them binding PPARG with dynamics reflecting its activation with full agonist rosiglitazone and correlating with increased levels of Sost transcript and sclerostin protein expression (Pearson’s r = 0.991, p = 0.001). Older γOTKO female mice are largely protected from TZD-induced bone loss providing proof of concept that PPARG in osteocytes can be pharmacologically targeted. These findings demonstrate that transcriptional activities of PPARG are essential for sclerostin expression in osteocytes and support consideration of targeting PPARG activities with selective modulators to treat osteoporosis.

Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM.

We examined 1700 community-dwelling Japanese men (≥65years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) ≥126mg/dl or glycated hemoglobin A

(HbA1c) ≥6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10years after baseline.

Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys.

OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.

OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.

The relative contribution of genetic and clinical factors for bone loss is not well known. This study aimed to investigate the annualized percentage change in total hip bone mineral density (BMD) and the genetic and clinical risk factors for bone loss in a Korean prospective cohort study over a 6-year period.

We included 645 men aged ≥50years and 683 postmenopausal women who had repeated BMD testing between 2007 and 2014. The association between covariates and annualized percentage change in hip BMD was analyzed through the multivariate linear regression analysis. A total of 2614 single-nucleotide polymorphisms (SNPs) from 23 known BMD-related candidate genes and genome-wise association study were investigated.

Hip bone loss increased more rapidly in women than in men with advancing age. Hip bone loss in men increased with lean mass (LM) loss (%/year) (P<0.001) and current smoking (P=0.024) and decreased with increasing waist circumference (WC) (P<0.001), alcohol consumption (P=0.049), and increasactors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.

In this study, decreasing WC and LM were significant risk factors for hip bone loss in both men and women. Those factors were also identified that had sex-specific or age-specific effects on hip bone loss. None of the SNPs were associated with hip bone loss after multiple testing adjustments. The understanding of the modifiable factors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.Osteogenesis imperfecta (OI) is a disease characterised by altered bone tissue material properties together with abnormal micro and macro-architecture and thus bone fragility, increased bone turnover and hyperosteocytosis. Increasingly appreciated are the soft tissue changes, sarcopenia in particular. Approaches to treatment are now multidisciplinary, with bisphosphonates having been the primary pharmacological intervention over the last 20 years. Whilst meta-analyses suggest that anti-fracture efficacy across the life course is equivocal, there is good evidence that for children bisphosphonates reduce fracture risk, increase vertebral size and improve vertebral shape, as well as improving motor function and mobility. The genetics of OI continues to provide insights into the molecular pathogenesis of the disease, although the pathophysiology is less clear. The complexity of the multi-scale interactions of bone tissue with cellular function are gradually being disentangled, but the fundamental question of why her that presents a treatment target in OI, remains to be established.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by impaired bone quality and quantity. Established imaging techniques have limited reliability in OI. The TX-Analyzer™ is a new, fractal-based software allowing a non-invasive assessment of bone structure based on conventional radiographs. We explored whether the TX-Analyzer™ can discriminate OI patients and healthy controls. Furthermore, we investigated the correlation between TX-Analyzer™ parameters and (i) bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DXA), (ii) trabecular bone score (TBS), and (iii) bone microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Data of 29 adult OI patients were retrospectively analyzed. Standard radiographs of the thoracic and lumbar spine were evaluated using the TX-Analyzer™. Bone Structure Value (BSV), Bone Variance Value (BVV), and Bone Entropy Value (BEV) were measured at the vertebral bodies T7 to L5. Data were compared to a healthy, age- and gele to discriminate patients with OI from healthy controls. ROC curves of BEV values suggest a suitable clinical applicability. Low to no correlations with conventional methods suggest, that the TX-Analyzer™ may indicate a new and independent examination tool in OI.

The software TX-Analyzer™ is able to discriminate patients with OI from healthy controls. ROC curves of BEV values suggest a suitable clinical applicability. Low to no correlations with conventional methods suggest, that the TX-Analyzer™ may indicate a new and independent examination tool in OI.

Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown.

Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and toll-like receptor (TLR)-3 stimulation in human lung macrophages.

Low doses of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased.

Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.

Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.

As the association between insulin resistance and ischaemic stroke is conflicting, our study aimed to examine the association between triglyceride-glucose (TyG), a surrogate marker of insulin resistance, and incident ischaemic stroke, and also to further assess the potential effect of modification by several known risk factors of stroke.

The Rural Chinese Cohort Study enrolled 11,777 participants, aged ≥40 years, who were free of stroke and cardiovascular disease at baseline during 2007-2008, and who were then followed during 2013-2014. TyG was determined using the following formula Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The relative risk (RR) and 95% confidence interval (CI) of incident ischaemic stroke associated with TyG were estimated using modified Poisson regression models.

During a median follow-up duration of 6 years, 677 new ischaemic stroke cases were identified. After multivariate adjustment, RR (95% CI) values for ischaemic stroke were 1.33 (1.01-1.75), 1.57 (1.17-2.10) and 1.95 (1.34-2.82) in TyG quartile (Q) 2, 3 and 4 groups, respectively, compared with Q1. A significant interaction between TyG index and age for risk of ischaemic stroke (P

 < 0.001) was also observed. However, no significant interaction was found between TyG index and other potential risk factors of risk for ischaemic stroke, although there were significant positive associations with female, non-smoker, non-drinker, low or moderate physical activity, non-obese and non-type 2 diabetes mellitus groups.

Elevated TyG index is an independent predictor of ischaemic stroke in the general population, and insulin resistance may be positively associated with future stroke risk.

Elevated TyG index is an independent predictor of ischaemic stroke in the general population, and insulin resistance may be positively associated with future stroke risk.

Type A personality-characterized by time urgency, strong drive, and a need for achievement and competitiveness-has been shown to be associated with reduced mortality in patients with diabetes. However, it is not known whether a Type A personality might protect against diabetic foot ulcer (DFU). This prompted our present analysis of the association between Type A personality and DFU.

The Bortner Scale questionnaire was used to assess Type A personality in 386 patients with type 2 diabetes (T2D), including 104 patients also presenting with, and 282 presenting without, DFU. Additional questionnaires were used to assess perceived stress and depression.

Type A Bortner scores were significantly lower in T2D patients with vs without DFU (166.64 ± 38.76 vs 178.79 ± 36.61, respectively; P = 0.005). In patients with DFU, the prevalence of Type A personality traits was significantly lower than in those without DFU (48% vs 64.5%, respectively; P = 0.005) whereas, in contrast, Type B personality traits (the opposite, might favour the development of DFU.The zebrafish (Danio rerio) has been considered a suitable model organism to assess the evolutionarily conserved bases of behavioral and neuroendocrine responses to stress. Depending on the nature of the stressor, prolonged stress may elicit habituation or evoke long-term changes in the central nervous systems (CNS) often associated with various neuropsychiatric disorders. Conspecific alarm substance (CAS) and net chasing (NC) constitute chemical and physical stressors, respectively, which cause aversive behaviors and physiological changes in fishes. Here, we investigate whether predictable chronic stress (PCS) using two homotypic stressors differently modulates behavioral and physiological responses in zebrafish. PCS-CAS or PCS-NC were performed for 14 days, 2-times daily, while locomotion, exploratory activity, anxiety-like behaviors, and whole-body cortisol levels were measured on day 15. PCS-CAS reduced distance traveled, the number of transitions and time in top area, as well as increased the latency to enter the top in the novel tank test. In the light/dark test, CAS-exposed fish showed decreased time spent in lit area, shorter latency to enter the dark area, and increased risk assessments. PCS-CAS also increased whole-body cortisol levels in zebrafish. Although PCS-NC reduced the latency to enter the dark area, whole-body cortisol levels did not change. Moreover, acute experiments revealed that both CAS and NC promoted anxiogenesis and increased cortisol levels, suggesting habituation to stress following PCS-NC. Overall, our novel findings demonstrate that PCS induces behavioral and physiological changes in zebrafish depending on the nature of the stressor.Sub-lethal exposure of dichlorvos induces oxidative stress, consequent genetic instability and apoptosis coupled with impairments in biochemical, histopathological and transcription of genes in Channa punctatus. Exposure of 5% (0.041 mg/L; E2) and 10% (0.082 mg/L; E3) of 96 h-LC50 of dichlorvos significantly (p less then 0.05) elevated the reactive oxygen species (ROS) generation and activities of SOD and CAT, as compared to control (E1) after 30 d. The maximum reduction in reduced glutathione (GSH) was recorded in the liver (18.53 ± 0.81 μg/mg of protein) and kidney (19.32 ± 0.97 μg/mg of protein); while the total protein contents were also found reduced, 278.38 ± 8.40 μg/mL (liver) and 248.44 ± 7.28 μg/mL (kidney), after 30 days in E3, in comparison to respective controls. Further, significant (p less then 0.05) induction in micronuclei (MN) and apoptotic cells (AC), in a dose- and exposure-based manner were also recorded. Moreover, a significant (p less then 0.05) up-regulation of p53 (2.51-fold in liver), bax (2.03-fold in liver; 1.99-fold in kidney) and casp3a (2.26-fold in liver; 2.10-fold in kidney) together with an elevated expression of cat (1.73-fold in liver; 1.12-fold in kidney), p53 (1.27-fold in kidney) and apaf-1 (1.72-fold in liver) in fish exposed to higher dose of dichlorvos for 30 d evidently reflects geno-toxicological potential of referenced pesticide. Disturbed biochemical and molecular parameters evince that the fish experienced oxidative stress as is further supported by prominent pathological observations in liver and kidney. Findings are, thus, helpful in organ-specific molecular scanning against aquatic toxicants like dichlorvos.The utilization of pesticides has increased for destroying pests and protecting crops in the agriculture field. Triazophos is a commonly used organophosphorous insecticide that causes alterations in haematological and histological parameters in fish. The present study was designed to evaluate the effect of triazophos induced innate and cell mediated immunotoxicity in freshwater teleost, Channa punctata. Fishes were exposed to triazophos at concentrations 5 and 10% of LC50 value for 10 and 20 days. Splenic and head kidney macrophage phagocytosis, nitric oxide production and superoxide production were assayed to evaluate the innate immunity. Cell-mediated immunity was measured through splenic and head kidney lymphocyte proliferation in presence of T and B cell mitogens. Results of the present study revealed that macrophage phagocytosis was significantly reduced after in vivo triazophos treatment. Differential suppressive effect of triazophos was also observed where mitogen induced splenic and head kidney lymphocyte proliferations were reduced after 10 and 20 days treatment. Concentration dependent effect of triazophos was observed in in vivo studies where the production of reactive oxygen and nitrogen intermediates were suppressed. This study describes the first investigation of the effect of triazophos on immune functions and will help to determine appropriate ecotoxicity and immunotoxicity in freshwater teleosts.

Obstructive sleep apnea is associated with increased risk of sudden cardiac death.

The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization.

In sedated spontaneously breathing pigs, 75 seconds of INAP was applied by a negative pressure device connected to the endotracheal tube. Ventricular electromechanical coupling was determined by the electromechanical window (EMW) before (pre-INAP), during (INAP), and after INAP (post-INAP). Incidence rates of premature ventricular contractions (PVCs) were measured respectively. A drug-induced LQT was modeled by treating the pigs with the hERG1 blocker dofetilide (DOF).

Whereas QT interval increased during and decreased after INAP (pre-INAP 273 ± 5 ms; INAP 281 ± 6 ms; post-INAP 254 ± 9 ms), EMW shortened progressively throughout INAP and post-INAP periods (pre-INAP 81 ± 4 ms; post-INAP 44 ± 7 ms).