After plasmapheresis, thyroidectomy was performed in 10 patients.

Plasmapheresis is an effective and safe treatment option for reducing circulating thyroid hormones in severe thyrotoxicosis when other forms of treatment are contraindicated or in case of urgent thyroid and non-thyroid surgery. It is limited by its cost and the need for highly specialized resources.

Plasmapheresis is an effective and safe treatment option for reducing circulating thyroid hormones in severe thyrotoxicosis when other forms of treatment are contraindicated or in case of urgent thyroid and non-thyroid surgery. It is limited by its cost and the need for highly specialized resources.Salt stress significantly induces accumulation of misfolded or unfolded proteins in plants. Endoplasmic reticulum (ER)-associated protein degradation (ERAD) and other degradative machineries function in the degradation of these abnormal proteins, leading to enhanced salt tolerance in plants. Here we characterise that a novel receptor-like kinase, Salt-Induced Malectin-like domain-containing Protein1 (SIMP1), elevates ERAD efficiency during salt stress through UMP1A, a putative proteasome maturation factor in Arabidopsis. SIMP1 loss-of-function caused a salt-hypersensitive phenotype. SIMP1 interacts and phosphorylates UMP1A, and the protein stability of UMP1A is positively regulated by SIMP1. SIMP1 modulates the 26S proteasome maturation possibly through enhancing the recruitment of specific β subunits of the core catalytic particle to UMP1A. Functionally, the SIMP1-UMP1A module plays a positive role in ERAD efficiency in Arabidopsis. The degradation of misfolded/unfolded proteins was impaired in both simp1 and ump1a mutants during salt stress. Consistently, both simp1 and ump1a plants exhibited reduced ER stress tolerance. Phenotypic analysis revealed that SIMP1 regulates salt tolerance through UMP1A at least in part. Taken together, our work demonstrated that SIMP1 modulates plant salt tolerance by promoting proteasome maturation via UMP1A, therefore mitigating ER stress through enhanced ERAD efficiency under saline conditions.This work aims to test the feasibility of a Fontinalis antipyretica devitalized moss clone to uptake and accumulate polycyclic aromatic hydrocarbons (PAHs) from surface waters. To assess the capability of the devitalized clone to accumulate PAHs, in the laboratory, moss was placed in water and spiked with increasing concentrations of 16 PAHs, and under field conditions, the moss was transplanted to 22 sites of Galicia (Spain) rivers. In general, PAH concentrations in water samples were lower than the maximum allowable concentrations from Directive 2013/39/EU, so the sampling sites did not show water PAH contamination. The exponential accumulation kinetic in the laboratory trial highlights a good capability of the devitalized moss clone to accumulate total PAHs. In field experiments, the hydrogeological conditions and the low emission sources caused low concentrations of PAHs in the water system and, consequently, in the transplants, although an enrichment can be observed for several PAHs. Overall, the devitalized clone of F. antipyretica can uptake and accumulate PAHs in water and may be useful in bioremediation strategies.The aquatic Lemnaceae family, commonly called duckweed, comprise some of the smallest and fastest growing angiosperms known on Earth. Their tiny size, rapid growth by clonal propagation, and facile uptake of labeled compounds from the media were attractive features that made them a well-known model for plant biology from 1950-1990. Interest in duckweed has steadily regained momentum over the past decade, driven in part by the growing need to identify alternative plants from traditional agricultural crops that can help tackle urgent societal challenges such as climate change and rapid population expansion. Propelled by rapid advances in genomic technologies, recent studies with duckweed again highlight the potential of these small plants to enable discoveries in diverse fields from ecology to chronobiology. Building on established community resources, duckweed is re-emerging as a platform to study plant processes at the systems level and to translate knowledge gained for field deployment to address some of society’s pressing needs. This review details the anatomy, development, physiology, and molecular characteristics of the Lemnaceae to introduce them to the broader plant research community. We highlight recent research enabled by Lemnaceae to demonstrate how these plants can be used for quantitative studies of complex processes and for revealing potentially novel strategies in plant defense and genome maintenance.An elderly Ethiopian-born patients developed end-stage kidney disease and haemodialysis was started. Shortly after, she developed some weight loss, lassitude, and diffuse body pain attributed to the ESKD, but also brief febrile episodes with non-contributory examination and work-up except for acute-phase response and mild cholestatic liver enzyme disturbance. Imaging revealed enlarged necrotic lymph nodes above and below the diaphragm. Needle biopsy was consistent with mycobacterium tuberculosis (TB) infection by pathology, PCR, and culture. TB is endemic in Africa and our patient had latent TB with reactivation due to her advanced age and especially, ESKD. The relatively subtle symptoms easily ascribed to ESKD are notable, as is the value of imaging, tissue diagnosis and PCR in establishing her widespread nodal extra-pulmonary tuberculosis. Current guidelines support screening foreign-born individuals who have recently immigrated. We suggest that when risk factors accumulate as in our patient (e.g. origin in an endemic area, ageing, hemodialysis), a routine interferon gamma release assay test is prudent, and positive patients may well benefit from chemoprophylaxis.

Increasingly, physicians find themselves in demanding leadership positions. However, leadership education for medical trainees remains lacking with most physicians reporting that they are ill-equipped to tackle the challenges of leadership. Here, we set out to describe the Feagin Leadership Program (FLP) and assess its reception and impact on trainees over the past 12 years.

During the 1-year FLP, selected scholars from Duke University, Wake Forest University, and the University of North Carolina participate in five leadership sessions, individual coaching, a leadership forum, and a multidisciplinary team-based capstone project. A 28-question survey with six optional free-response questions was distributed to the Feagin Alumni Network, and descriptive statistics were assessed.

Since its founding, 212 scholars have graduated from the FLP and 117 (55%) alumni have gone on to surgical specialties. A survey was distributed among all Feagin alumni. A total of 56 (26%) surveys were completed. Forty-three percof leadership education for surgical trainees can best be addressed with models such as the FLP, with adoption benefiting medical trainees, the medical community, and patients they serve.Healthcare workers have never faced a medical crisis that compares to the coronavirus disease-2019 pandemic. This modern-day pandemic fight draws parallels to a war. Because of these similarities, it would make sense that the experiences frontline providers have when transitioning to a normal healthcare routine would emulate experiences service members voice when reintegrating home from a battlefield. These common experiences include a unified mission, an exhausting, adrenaline-packed responsibility, and a celebrity-like status to the public. The pandemic response consumed healthcare with one united mission, but as we reemerge from the pandemic and restore other aspects of our healthcare system, multiple missions develop and compete. Returning to a common routine and regular status can manifest feelings of disappointment in healthcare workers’ everyday lives and career choices and lead to a reexamination of priorities and professions. As an organization with a focus on high reliability, mitigating the harm tomproving the lifelong well-being of our caregivers.Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.

To identify individual-level factors associated with hospital readmission among individuals with systemic sclerosis associated pulmonary hypertension (SSc-PH).

Individuals enrolled in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) registry contributed clinical data related to SSc-PH disease severity and hospital admissions. Readmission was defined as a subsequent hospitalization within 12 months of any hospital discharge. Characteristics were compared between individuals with and without readmissions using Fisher’s exact test, Wilcoxon rank-sum test, or Kruskal Wallis test. Logistic regression was used to estimate associations between clinical predictors and likelihood of readmission.

Of 572 individuals with SSc-PH enrolled in PHAROS, 54% had ≥1 hospitalizations between 2005 and 2016. Among individuals ever-hospitalized, 34% had ≥1 readmission. Individuals with vs without readmissions had shorter median (IQR) time between index hospitalization date and next PHAROS visit (37 (3, 80) vs 81 (42, 136) days, p< 0.001). Index admissions related to PH or SSc (vs non-PH/SSc related) were associated with an increased odds of 12-month readmission (aOR 6.6 (95% CI 3.2, 13.6) and aOR 2.2 (95% CI 1.1, 4.5), respectively). Readmission was less likely among home oxygen users (vs non-users) (aOR 0.44; 95% CI 0.22, 0.89). Race, age, sex, disease duration, and disease subtype were not associated with readmission.

The strongest predictor for 12-month readmission was an index hospitalization reason related to PH. Home oxygen use was associated with lower odds of readmission. Future studies should determine whether testing for the need for home oxygen mediates the risk of readmission in SSc-PH.

The strongest predictor for 12-month readmission was an index hospitalization reason related to PH. Home oxygen use was associated with lower odds of readmission. Future studies should determine whether testing for the need for home oxygen mediates the risk of readmission in SSc-PH.

Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms.

We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed-tomography (µCT)-scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; p < 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine induced human primary VSMC calcification, increased osteogenic gene expression (Runx2, Osx, BSP and OPN), and extracellular vesicle (EV) s release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.

In this study we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.

Police are frequently exposed to occupational trauma, making them vulnerable to post-traumatic stress disorder (PTSD) and other mental health conditions. Through personal and occupational trauma police are also at risk of developing Complex PTSD (CPTSD), associated with prolonged and repetitive trauma. Police Occupational Health Services require effective interventions to treat officers experiencing mental health conditions, including CPTSD. However, there is a lack of guidance for the treatment of occupational trauma.

To explore differences in demographics and trauma exposure between police with CPTSD and PTSD and compare the effectiveness of brief trauma-focused therapy between these diagnostic groups.

Observational cohort study using clinical data from the Trauma Support Service, providing brief trauma-focused therapy for PTSD (cognitive behavioural therapy/eye movement desensitization and reprocessing) to UK police officers. Demographics, trauma exposure, baseline symptom severity and treatment effen and relational difficulties) are also reduced.

Peripheral muscle involvement in systemic sclerosis (SSc) may comprise myositis or a non-inflammatory myopathy. There is little understanding on the nature of SSc myopathy. This pilot study aimed to evaluate for the presence of diffuse fibrosis in the peripheral muscle of patients with SSc by determining extracellular volume (ECV) MRI measurement.

SSc patients, with suspected myopathy or no muscle involvement, and healthy volunteers (HV) had native T1 and ECV MRI quantification of the thigh and creatine-kinase (CK) measured. Suspected myopathy was defined as current/history of minimally raised CK (<600 IU/l) +/- presence of clinical signs-symptoms (proximal muscle weakness and/or myalgia) +/- a Manual Muscle Testing score <5 in the thighs.

12 SSc patients and 10 HV were recruited. 9/12 patients had limited cutaneous SSc, 4/12 interstitial lung disease, 7/12 suspected myopathy. Higher skeletal muscle ECV was recorded in SSc patients compared to HV [mean (SD) 23(11)%, vs 11(4)% p = 0.04].Peripheral muscle ECV associated with CK (rho=0.554, p = 0.061) and was higher in SSc patients with myopathy compared to those with no myopathy [mean (SD) 28 (10) vs 15 (5), p = 0.023]. An ECV of 22% was determined to best identify myopathy with a sensitivity of 71% and a specificity of 80%.

This hypothesis-generating study showed higher ECV in SSc patients compared to HV as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.

This hypothesis-generating study showed higher ECV in SSc patients compared to HV as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.Intrusive leadership is a method that looks for signs that might indicate a problem within or outside of the workplace that can affect a member’s performance and, subsequently, the mission. Our scenario demonstrates how intrusive leadership can identify potential problems which, when coupled with accountability, can prevent more significant complications.

Subjective loss of response immediately prior to routine TNFi therapy can occur in axial spondyloarthritis (axSpA). We investigated clinical outcomes in patients taking the first 3 licenced TNFis and correlated this with recurrence of MRI bone marrow oedema (MRI-BMO).

Proof-of-concept study including axSpA patients established on etanercept (ETA), adalimumab (ADA) or infliximab (IFX) reporting symptom deterioration prior to next dose. MRI/clinical data were collected prior to scheduled dose (v1), 4 days post-dose (v2) and at the time of patient-reported symptom return (v3). MRI spine/sacroiliac joints utilising 3 T were scored using the semi-quantitative Leeds MRI scoring system.

113 clinical assessments and MRIs were performed in 38 participants (ADA = 16, ETA = 12, IFX = 10), mean age 42.1 years ± 24.4(2SD, n = 38), 71.1% male (n = 27/38), 69.7% HLA-B27 positive (n = 23/33). At v1 all patients had high disease activity [ASDAS-CRP = 3 (2.7-3.7)] and 57.9% had MRI-BMO (number of MRI-BMO ETA = 26, ADA = 59, IFX = 28). Improved clinical responses were seen at v2 [ASDAS-CRP -0.41(-0.81-0.30), p= 0.018; BASDAI -0.58(-2.2-0.52), p= 0.024]. Despite just a 4-day interval between v1 and v2, a numerical reduction in MRI-BMO lesions between v1/v2 was observed (ETA=-6, ADA=-10, IFX=-3). By v3 comparatively fewer new BMO lesions were detected in the ETA and ADA groups compared with IFX (ETA=-1, ADA = +3, IFX = +8), although the numbers were too small to enable testing for statistical significance.

Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are need to confirm the possible pathogenic implications of this phenomenon.

Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are need to confirm the possible pathogenic implications of this phenomenon.

Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel’s lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live-actor patients using a wearable training apparatus was developed, and the effects of this method were observed.

Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live-actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live-actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year ctical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live-actor patients were more helpful in the training of injury evaluation than high-fidelity simulators.

The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.

The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.

The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC.

Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC.

Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC.

Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Limited data about use of biosimilars are available in children with Juvenile Idiopathic Arthritis (JIA). This study therefore aimed to evaluate long-term efficacy and safety of switching from etanercept (ETA) and adalimumab (ADA) originators to their biosimilars, in children with JIA, in a real-world setting.

This is a retro-prospective non-interventional multicentre Italian comparative cohort study. Medical charts of JIA children treated with biosimilars of ETA or ADA were included. Efficacy and safety of TNF-inhibitors therapy was evaluated at last follow-up during originator and at 3, 6 and 12 months following the switch to biosimilar.

59 children (42 female, median age at onset 88 months) were treated with biosimilar of ETA (21) and ADA (38). Forty-five switched from the originator to the BIO (17 ETA, 28 ADA). At time of switch, 12/17 patients on ETA and 18/28 on ADA were in remission. No significant difference has been found at 3, 6 and 12 months after the switch. Ten patients discontinued biosimilars due to disease remission (4 ETA, 3 ADA), family willing (1 ETA), occurrence of burning at injection site (1 ETA), and persistent activity (1 ADA). No statistically significant difference was observed between originator and BIOs, nor between originator and BIOs, and between ADA and ETA in time to disease remission achievement, time to relapse and number of patients who experienced AE.

Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs also in paediatric patients with JIA.

Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs also in paediatric patients with JIA.

Recent advances in cardiac magnetic resonance imaging (CMR) and other diagnostic techniques have made it easier to identify subclinical cardiac inflammation and dysfunction in the idiopathic inflammatory myopathies (IIM). Herein, we systematically review the literature regarding cardiac involvement in IIM.

We searched Medline and EMBASE from 1990-2020 using keywords related to IIM and cardiac disease. We included English language studies in adults with any immune-mediated, inflammatory muscle pathology.

We identified 10425 potentially relevant abstracts, of which 29 were included. Most frequently these included patients with polymyositis or dermatomyositis without symptomatic myocarditis. Five categories of cardiac investigation were used in these patients cardiac enzyme testing, electrocardiography (ECG), transthoracic echocardiography (TTE), CMR and nuclear medicine testing. Patients with clinical myocarditis had universally abnormal cardiac troponin levels and ECG. Elevated cardiac troponin T was more common than troponin I (cTnI) and may correlate with disease activity, whereas cTnI was more specific for cardiac involvement. Non-specific ECG changes were common. The major finding on TTE was abnormal ejection fraction. Gross systolic dysfunction was unusual, but subclinical systolic dysfunction was reported in several studies. Abnormal diastolic function was common and may be associated with disease duration. Late gadolinium enhancement (reflecting regional necrosis or scar) and abnormal myocardial mapping parameters (reflecting myocardial inflammation, fibrosis and oedema) were frequently identified on CMR, suggesting significant subclinical myocardial pathology (despite typically normal ejection fraction).

Abnormal cardiac investigations are commonly found in asymptomatic IIM patients, which has potential prognostic and treatment implications.

Abnormal cardiac investigations are commonly found in asymptomatic IIM patients, which has potential prognostic and treatment implications.

Heart rate (HR) is a critical indicator of cardiac performance that is determined by sinoatrial node (SAN) function and regulation. Natriuretic peptides, including C-type NP (CNP) have been shown to modulate ion channel function in the SAN when applied exogenously. CNP is the only NP that acts as a ligand for natriuretic peptide receptor-B (NPR-B). Despite these properties, the ability of CNP and NPR-B to regulate HR and intrinsic SAN automaticity in vivo, and the mechanisms by which it does so, are incompletely understood. Thus, the objective of this study was to determine the role of NPR-B signaling in regulating HR and SAN function.

We have used NPR-B deficient mice (NPR-B+/-) to study HR regulation and SAN function using telemetry in conscious mice, intracardiac electrophysiology in anesthetized mice, high resolution optical mapping in isolated SAN preparations, patch-clamping in isolated SAN myocytes, and molecular biology in isolated SAN tissue. These studies demonstrate that NPR-B+/- mice exhibit smyocytes via a cGMP/PDE3/cAMP signaling mechanism.Sertoli cells are cells that provide protection and nutrition for developing sperm. Each stage of sperm development occurs on the surface of Sertoli cells. MicroRNA (MiR)-125a-5p is involved in male reproduction. The current research aimed to probe the role of miR-125a-5p in Sertoli cell function. Functionally, miR-125a-5p knockdown facilitated Sertoli cell proliferation, while miR-125a-5p overexpression suppressed Sertoli cell proliferation, as evidenced by 5-ethynyl-20-deoxyuridine incorporation assay. Additionally, miR-125a-5p knockdown inhibited Sertoli cell apoptosis, while miR-125a-5p upregulation facilitated Sertoli cell apoptosis, as evidenced by flow cytometry analysis. Computationally, we identified four predicted mRNA targets of miR-125a-5p. Based on the results of luciferase reporter assay, miR-125a-5p was confirmed to bind to the predicted sequence in the Ras-related protein Rab-3D (RAB3D) 3’UTR. Rescue experiments showed that miR-125a-5p suppressed the proliferative ability of TM4 Sertoli cells and facilitated their apoptosis by targeting RAB3D. Finally, our data confirmed that miR-125a-5p and RAB3D modulated activation of the PI3K/AKT pathway. In conclusion, our data showed that miR-125a-5p regulated Sertoli cell proliferation and apoptosis by targeting RAB3D and regulating the PI3K/AKT pathway.Enterotoxigenic Escherichia coli (ETEC) are ubiquitous diarrheal pathogens that thrive in areas lacking basic human needs of clean water and sanitation. These genetically plastic organisms cause tremendous morbidity among disadvantaged young children, both in the form of acute diarrheal illness and sequelae of malnutrition and growth impairment. The recent discovery of additional plasmid-encoded virulence factors and elucidation of their critical role in the molecular pathogenesis of ETEC may inform new approaches to the development of broadly protective vaccines. Although these pathogens have been closely linked epidemiologically with non-diarrheal sequelae, these conditions remain very poorly understood. Similarly, while canonical effects of ETEC toxins on cellular signaling promoting diarrhea are clear, emerging data suggest that these toxins may also drive changes in intestinal architecture and associated sequelae. Elucidation of molecular events underlying these changes could inform optimal approaches to vaccines that prevent acute diarrhea and ETEC-associated sequelae.

How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined.

To study whether BRAF V600E affected LNM-associated mortality in PTC.

We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 (IQR 35-58) years and median follow-up time of 58 (IQR 26-107) months.

Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAFV600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAFV600E patients; mortality rates were 2/659 (0.3%) versus 4/321 (1.2%) in non-LNM versus LNM patients (P=0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAFV600E CPTC, morality rates were 7/515 (1.4%) versus 28/363 (7.7%) in non-LNM versus LNM patients (P<0.001), corresponding to HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAFV600E versus absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism.

LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.

LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.

As part of their day-to-day operational mission, shipboard sailors experience unique stressors that can affect their health and readiness. The San Diego Fleet and Family Support Center (FFSC) conducts in-person classes to teach stress management principles to sailors. The FFSC stress management course covers the causes and consequences of stress, reviews the Navy Operational Stress Control model, and provides information on basic stress management skills. This course has not been rigorously evaluated to determine its impact on the sailors’ ability to manage stress. The purpose of this study was to evaluate the short-term impact of the FFSC stress management class on the (1) sailors’ stress management knowledge, (2) sailors’ intention to share knowledge from the class with others, and (3) sailors’ satisfaction with the class.

Shipboard sailors (n = 95) who attended a stress management course completed pretest and posttest assessments that measured workplace stress, current stress management behaviors, stre team from assessing the long-term impact of the stress management course on future stress levels and stress abatement behaviors. Recommendations are made to enhance future evaluations of FFSC classes for service members.

This study was the first evaluation of the short-term impact of the FFSC stress management course on the stress management knowledge of shipboard crews. Study limitations prevented the study team from assessing the long-term impact of the stress management course on future stress levels and stress abatement behaviors. Recommendations are made to enhance future evaluations of FFSC classes for service members.Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression, and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases=59,674; n controls=316,078), bipolar disorder (n cases=20,352; n controls=31,358), depression (n cases=170,756; n controls=328,443) and schizophrenia (n cases=40,675, n controls=64,643). We applied the bivariate causal mimigraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2, SLC9B1. Gene-set analysis identified several putative gene-sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of 'pleiotropic’ variants which influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation.Environmental enteric dysfunction (EED) is a syndrome characterised by impairments of digestion and absorption and intestinal barrier failure in people living in insanitary or tropical environments. There is substantial evidence that it contributes to impaired linear growth of millions of children in low- and middle-income countries, to slowed neurocognitive development, and to diminished responses to oral vaccines. It represents the functional consequences of environmental enteropathy, an asymptomatic inflammatory disorder of the mucosa, and there is considerable overlap with the enteropathy observed in severe clinical malnutrition. The majority of studies of EED have employed functional tests based on lactulose permeation to define the presence of abnormal leak in the gut. However, where intestinal biopsies can safely be collected the opportunity then arises to study the underlying enteropathy in cellular and molecular detail, as well as to measure important functional elements such as enzyme expression. The purpose of this narrative review is to summarise the current understanding of environmental enteropathy (EE) obtained from small intestinal biopsies, and prospects for future work. We review histology, electron microscopy, transcription and protein expression, physiological measures, and the microbiome. We conclude that while non-invasive biomarkers of enteropathy and intestinal dysfunction permit large scale studies of unquestionable value, intestinal biopsies are still required to investigate pathophysiology in depth.

This review describes the processes and effectiveness of the primary management systems that structure and sustain consistent behaviors and result in a transformed culture of continuous quality improvement (CQI) from top to bottom throughout the Henry Ford medical laboratory enterprise.

Through a 17-year focus to achieve a functional CQI enterprise, quality management systems were developed and continuously improved by teams of laboratory leaders, managers, and quality specialists to coordinate and standardize human efforts, and provide actionable knowledge and data to engage improvement efforts at all levels of work. Lean and ISO 15189 discipline and requirements were addressed in annual management review of functionality and effectiveness to close gaps and further refine the management systems.

Improvements in the use and effectiveness of 4 management systems are illustrated.

The 4 primary management systems that provide structure and support transformation to a culture of CQI are the team leader, Plan-Do-Check-Act problem-solving, deviation management, and daily management systems. These management systems are designed to deepen the effectiveness of the continuous improvement culture by helping managers understand variation in the work they oversee and providing guidance for more effective employee engagement in the daily processes of quality improvement.

The 4 primary management systems that provide structure and support transformation to a culture of CQI are the team leader, Plan-Do-Check-Act problem-solving, deviation management, and daily management systems. These management systems are designed to deepen the effectiveness of the continuous improvement culture by helping managers understand variation in the work they oversee and providing guidance for more effective employee engagement in the daily processes of quality improvement.

To complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human-virus protein-protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving prediction performance.

To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron. Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two transfer learning methods (i.e., 'frozen’ type and 'fine-tuning’ type) that reliably predict interactions in a target human-virus domain based on training in a source human-virus domain, by retraining CNN layers. Finally, we utilize the 'frozen’ type transfer learning approach to predict human-SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Diabetes has been known since antiquity. We present here a historical perspective on the concepts and ideas regarding the physiopathology of the disease, on the progressive focus on the pancreas, in particular on the islets discovered by Langerhans in 1869, leading to the iconic experiment of Minkowski and von Mering in 1889 showing that pancreatectomy in a dog induced polyuria and diabetes mellitus. Subsequently, multiple investigators searched for the active substance of the pancreas and some managed to produce extracts that lowered blood glucose and decreased polyuria in pancreatectomized dogs, but were too toxic to be administered to patients. The breakthrough came 100 years ago when the team of Frederick Banting, Charles Best and James Collip working in the Department of Physiology headed by John Macleod at the University of Toronto managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available. This achievement was quickly recognized by the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923. At 32, Banting remains the youngest awardee of this Prize. Here we discuss the work that led to the discovery and its main breakthroughs, the human characters involved in an increasingly dysfunctional relationship, the controversies that followed the Nobel Prize, and the debate as to who actually „discovered” insulin. We also discuss the early commercial development and progress in insulin crystallization in the decade or so following the Nobel Prize.We retrospectively analyzed the clinical data from 39,185 cycles who undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in the First People’s Hospital of Shangqiu, these poor ovarian reserve patients were further categorized into the „unexpected” group (n=3337) and the „expected” group (n=2667) based on POSEIDON classification. In „expected” group, logistic regression analysis showed that female age (OR 0.920; 95% C.I 0.902~0.939; P less then 0.001), treatment cycles (OR 0.693; 95% C.I 0.560~0.859; P = 0.001), duration of Gn administered (OR 1.077; 95% C.I 1.027~1.129; P = 0.002) and transferable embryos (OR 1.377; 95% C.I 1.319~1.437; P less then 0.001) is independent predictive factors of live birth. In „expected” group, logistic regression analysis showed that female age (OR 0.874; 95% C.I 0.848~0.900; P less then 0.001), AFC (OR 1.285; 95% C.I 1.131~1.461; P less then 0.001), total dosage of Gn administered (OR 1.001; 95% C.I 1.000~1.002; P less then 0.001), duration of Gn administered (OR 0.784; 95% C.I 0.639~0.961; P = 0.019), MII number (OR 0.841; 95% C.I 0.717~0.986; P = 0.032) and transferable embryos (OR 2.057; 95% C.I 1.762~2.400; P less then 0.001) is independent predictive factors of live birth. We also established a smooth curve fit to predict the probability of live birth among the POSEIDON „unexpected” and „expected” group. These independent predictive factors on the pregnancy outcome of IVF/ICSI and the successful establishment of smooth curve fit can provide valuable reference for treats poor ovarian reserve patients in clinical work.

We investigated association of a score incorporating relative grip strength (RGS) and timed up and go (TUG) test with incident type 2 diabetes mellitus (T2DM) in older Chinese.

Both RGS and TUG scores were classified into tertiles (0~2 points) and summed to yield RGS-TUG score, ranging from 0 to 4 points, with higher points indicating better physical function. Cox proportional hazards regression was used to analyze association of RGS-TUG score with incident T2DM.

3,892 participants without T2DM were followed up for an average of 3.6 years with 240 developing T2DM. After adjustment, those with the lowest RGS-TUG score, versus the highest, had higher fasting glucose, two-hour post-load glucose and glycosylated hemoglobin A1c, with β (95% confidence interval (CI)) being 0.21 (0.08, 0.33), 1.06 (0.69, 1.43) and 0.16 (0.06, 0.27), respectively. In participants with BMI of ≥25 kg/m2, those with the lowest RGS-TUG score showed a higher risk of T2DM (adjusted hazard ratio 3.01, 95% CI 1.04-8.69). No association was found for BMI of 18.5~<25 kg/m2 (P for interaction < 0.05).

This is the first study showing lower RGS-TUG score was associated with increased glycemia and incident T2DM in older people with overweight/obesity. The underlying mechanisms warrant further investigation.

This is the first study showing lower RGS-TUG score was associated with increased glycemia and incident T2DM in older people with overweight/obesity. The underlying mechanisms warrant further investigation.

Despite the availability of cystic fibrosis (CF) screening countrywide, diagnostic delay is still a crucial issue. The objectives of this study were to explore the stages of the NBS process, determine the risk factors associated with diagnostic delay and evaluate parent anxiety and experience throughout the process.

This is a multicenter cross-sectional study. A questionnaire was completed by parents of newborns diagnosed with CF via NBS in 17 centers. Socio-demographic characteristics, parent knowledge and experiences related to NBS, sweat test availability in the region of residence, and time to the definitive CF diagnosis were assessed through this questionnaire. Parents’ anxiety levels were evaluated through the State-Trait Anxiety Inventory scales 1 and 2. Delayed diagnosis (DD) was defined as a definite CF diagnosis beyond the 8th week of life. Predictors of delayed CF diagnosis were evaluated by univariate and multivariate analysis.

A total of 220 CF patients diagnosed via NBS were enrolled; 82 (37.3%) babies had DD. Multivariable analysis indicated that residence in the Southeast Anatolia region of Turkey (OR = 10.79, 95% CI = 2.37-49.2) was associated with a higher incidence of DD compared with other regions in Turkey. Of the total, 216 (98.1%) of the caregivers regarded the NBS program as useful and 180 (82%) reported high anxiety levels.

The organization of newborn screening should take into account regional and socio-cultural characteristics to improve the early diagnosis of CF and also reduce the anxiety level of parents.

The organization of newborn screening should take into account regional and socio-cultural characteristics to improve the early diagnosis of CF and also reduce the anxiety level of parents.

Repeat pulmonary resection is widely accepted in clinical practice. This study aimed to compare sublobar resection (segmentectomy or wedge resection) with lobectomy in the treatment of patients who underwent a second pulmonary resection.

This study retrospectively included patients who underwent lobectomy or sublobar resection for second pulmonary resection. 11 propensity score matching (PSM) was performed to balance selection bias. Clinicopathological features, perioperative and survival outcomes of lobectomy and sublobar resection were compared.

A total of 308 patients who underwent second pulmonary resection were identified 71 (23.1%) who underwent lobectomy and 237 (76.9%) who underwent sublobar resection. After PSM, 58 patients for each group were selected with well-balanced clinicopathological characteristics. In patients who underwent sublobar resection, significantly shorter chest tube duration (days) (median, 4 vs. 2, p < 0.001) and postoperative hospital stay (days) (median, 6 vs. 4, p < 0.001) were observed. There was no significant difference in overall survival between these two groups after the second and first surgery (p=0.65, p=0.98), respectively. Subgroup analysis according to the type of the first resection showed consistent results.

Sublobar resection may be considered as an alternative option for second pulmonary resection due to its perioperative advantages and similar survival outcomes compared with lobectomy.

Sublobar resection may be considered as an alternative option for second pulmonary resection due to its perioperative advantages and similar survival outcomes compared with lobectomy.Pseudocirrhosis is a radiological diagnosis of cirrhosis without histological evidence and occurs as a complication of liver metastases from solid tumors. A 50-year-old man without any previous history of liver disease was diagnosed with adenocarcinoma of the left upper lung lobe and liver metastasis. After chemotherapy, the liver metastases shrank; however, over time, the liver shrank and showed cirrhosis-like morphological changes. His performance status deteriorated due to ascites and leg edema, and chemotherapy was terminated. Physicians treating lung adenocarcinoma with liver metastases should be aware that pseudocirrhosis is a rare but important complication that can worsen performance status (PS) and hinder treatment continuation.

There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression-free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score.

This was a post hoc analysis of a multicenter, double-blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively.

The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI 3.5-11.0) versus 3.2 (95% CI 1.2-5.3) months, p=0.001; HR (95% CI), 0.4 (0.2-0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI 3.0-11.0) vs. 4.8 (95% CI 1.2-8.5) months (p=0.043). No statistically significant differences were found in OS in the stratified analyses.

The occurrence of hypertension might be a clinical indicator predicting the efficacy of third-line anlotinib treatment in patients with SCC.

The occurrence of hypertension might be a clinical indicator predicting the efficacy of third-line anlotinib treatment in patients with SCC.

The aim of this study is to describe ratio and skill mix for nursing staff in Swedish emergency departments over a specific 24-h period.

The link between number of patients per nursing staff and missed nursing care is well described within the in-hospital setting, showing association with negative outcomes such as increased mortality. Potential association within the emergency department setting is still unexplored.

This is a national descriptive cross-sectional benchmark study.

The majority (n= 54; 89%) of Swedish emergency departments participated. The patients-per-registered nurse ratio varied between the shifts, from 0.3 patients to 8.8 patients (mean 3.2). The variation of patients per licenced practical nurse varied, from 1.5 to 23.5 patients (mean 5.0). The average skill mix was constant at around 60% registered nurses and 40% licenced practical nurses.

The varying ratios for patient per registered nurse and licenced practical nurse in Swedish emergency departments are noteworthy. Furthermore, the patient flow and nursing staff numbers did not match one another, resulting in higher nursing staff ratios during the evening shift.

Findings can be used to improve rosters in relation to crowding, to manage the challenging recruitment and retention situation for nursing staff and to improve patient safety.

Findings can be used to improve rosters in relation to crowding, to manage the challenging recruitment and retention situation for nursing staff and to improve patient safety.Dopamine D1 receptors play an important role in the effects of cocaine. Here, we investigated the role of neurons which express these receptors (D1-neurons) in the acute locomotor effects of cocaine and the locomotor sensitization observed after a second injection of this drug, using the previously established two-injection protocol of sensitization. We inhibited D1-neurons using double transgenic mice conditionally expressing the inhibitory Gi-coupled designer receptor exclusively activated by designer drugs (Gi-DREADD) in D1-neurons. Chemogenetic inhibition of D1-neurons by a low dose of clozapine (0.1 mg/kg) decreased the cocaine-induced expression of Fos in striatal neurons. It diminished the basal locomotor activity and acute hyper-locomotion induced by cocaine (20 mg/kg). Clozapine 0.1 mg/kg had no effect by itself and did not alter cocaine effects in wild-type mice. Inhibition of D1-neurons during the first cocaine administration prevented the sensitization of the locomotor response in response to a second cocaine administration 10 days later.