The diagnosis of type 1 diabetes mellitus (DM) in humans is associated with high altitude, few sunshine hours, cold climate, and winter. The goals of this study were to investigate seasonal and ...geographic patterns of DM diagnosis in United States of America (USA) dogs with juvenile and mature onset DM. Data were collected by means of an online survey widely distributed in the USA through breed clubs, academic veterinary institutions, private veterinary referral practices, social media outlets, and the American Kennel Club. Juvenile DM (JDM) and mature onset DM were defined as DM with an age of onset <365 days and DM with an age of onset ≥365 days, respectively. Meteorological seasons were defined as: winter from December through February, spring from March through May, summer from June through August, and fall from September through November. Four geographic regions were also defined as the West, North, South, and Central regions of the USA. Nonoverlapping 95% confidence intervals (CI) for season, geographic region, and breed specific proportions of dogs with JDM were considered statistically significantly different. The study included 933 dogs with mature onset DM and 27 dogs with JDM. Dogs were diagnosed with DM significantly more in the winter and northern USA compared to all other seasons and all other geographic regions, respectively. The prevalence of JDM among dogs with DM was 2.8%. The proportion of dogs with JDM among pure breeds was not significantly different than the proportion of JDM in mixed breed dogs. It is concluded that winter and cold climate could be shared environmental factors influencing DM expression in dogs and humans. Additionally, pure breed dogs do not appear to be at increased risk for JDM compared to mixed breed dogs, indicating that factors other than genetics could influence spontaneous JDM development in dogs.
Summary
Numerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis. To summarize our ...current understanding of the role of leptin in inflammatory responses and rheumatoid arthritis (RA), a systematic review was conducted to assess the discrepancy of leptin in RA and its effect on immunity according to different studies. Recently, emerging data have indicated that leptin is involved in the pathological function of RA, which is common in autoimmune disorders. This review discusses the possible consequences of leptin levels in RA. Blocking the key signal pathways of leptin and inhibiting the leptin activity‐like leptin antagonist may be a promising way for potential therapeutic treatment of RA at risk of detrimental effects. However, leptin was increased in patients with RA and may also regulate joint damage. Thus, more understanding of the mechanism of leptin in RA would be advantageous in the future.
A nanocrystalline (NC) face-centered cubic FeNi2CoMo0.2V0.5 high-entropy alloy was produced by high pressure torsion (HPT). The evolutions of microhardness and microstructure of the NC alloy during ...subsequent isochronal annealing were investigated systematically by electron back-scattering diffraction (EBSD) and high-resolution transmission electron microscopy (HRTEM). It was found that nano-grains and deformation nano-twin lamella were obtained at outer disk edge after HPT process with a hardness plateau of 450 HV. Isochronal annealing below 600 °C induced an evident hardening without precipitation effect, due to the annihilation of mobile dislocations and sustained deformation twin barriers. Evident recrystallization and grain growth of the NC FeNi2CoMo0.2V0.5 high-entropy alloy occurred during isochronal annealing at temperatures higher than 600 °C. The activation energies of recrystallization and grain growth of the NC FeNi2CoMo0.2V0.5 high-entropy alloy were calculated to be 350 kJ/mol and 272 kJ/mol, respectively, corresponding to a slow defects recovery process and a swift GB migration process. The high thermal stability of the NC FeNi2CoMo0.2V0.5 high-entropy was mainly caused by kinetic sluggish diffusion effect and deformation twin boundaries with thermodynamic low boundary energy, which retarded the movements of dislocations and grain boundary.
The identification of loss-of-function mutations in MKRN3 in patients with central precocious puberty in association with the decrease in MKRN3 expression in the medial basal hypothalamus of mice ...before the initiation of reproductive maturation suggests that MKRN3 is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In the current study, we investigated the mechanism by which MKRN3 prevents premature manifestation of the pubertal process. We showed that, as in mice, MKRN3 expression is high in the hypothalamus of rats and nonhuman primates early in life, decreases as puberty approaches, and is independent of sex steroid hormones. We demonstrated that Mkrn3 is expressed in Kiss1 neurons of the mouse hypothalamic arcuate nucleus and that MKRN3 repressed promoter activity of human KISS1 and TAC3, 2 key stimulators of GnRH secretion. We further showed that MKRN3 has ubiquitinase activity, that this activity is reduced by MKRN3 mutations affecting the RING finger domain, and that these mutations compromised the ability of MKRN3 to repress KISS1 and TAC3 promoter activity. These results indicate that MKRN3 acts to prevent puberty initiation, at least in part, by repressing KISS1 and TAC3 transcription and that this action may involve an MKRN3-directed ubiquitination-mediated mechanism.
Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors ...(TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study.
Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis.
EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments.
EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and 'second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.
Purpose
This retrospective study aimed to assess the association between obesity, gender, and specific clinicopathological features in patients with papillary thyroid cancer (PTC) and whether ...diagnostic ultrasonography (US) is adversely affected by obesity in these patients.
Materials and methods
This study retrospectively analyzed 13,995 adult patients with PTC from a single medical center in China. Data stratification was performed to assess the association of obesity with US features and aggressive clinicopathological features in different models according to the World Health Organization Body Mass Index (WHO-BMI) and Chinese BMI classification (CN‐BMI). The odds ratio (OR) of malignant US features and aggressive clinicopathological features was calculated from binary logistic regression models.
Results
The BMI, obesity ratio, malignant US features, and aggressive pathological characteristics of males were significantly higher than those of females. After adjusting for confounding factors, the association of obesity with malignant US features and aggressive pathological characteristics was found to be sex-dependent. Next, obesity (WHO-BMI) was found to have an “interfering effect” on the US assessment of PTC (OR = 0.754, 95% CI 0.609–0.932,
P
= 0.009) in women. Among both sexes, obesity (WHO-BMI) increased the risk of tumor size (OR
male
= 1.539 and OR
female
= 1.521) and multifocality (OR
male
= 1.659 and OR
female
= 1.449). However, obesity did not increase the risk of capsular invasion or tumor staging in males. The above results are consistent with the CN-BMI. In addition, age was found to have an “interfering effect” on the US evaluation of malignant nodules in both sexes.
Conclusion
The results of our study confirm that higher BMI is significantly associated with aggressive clinicopathological features of PTC. Gender differences were present with obesity ratios and aggressive clinicopathological features being significantly higher in men.
Objective
We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices ...among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019.
Methods
The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25–February 25, 2020), phase II (February 26–March 19), phase III (March 20–April 20).
Results
There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (
P
= 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital.
Conclusion
The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have gained increasingly global attention in recent years. Due to their unique amphiphilic properties and stability, PFASs are recognized as ...highly persistent, toxic, and environmentally bioaccumulative. Among several physicochemical technologies, adsorption has been extensively used and proved to be an effective method for removing PFASs from aqueous environment. In this review article, the technical feasibility of the use of different adsorbents, such as activated carbon, ion exchange resins, minerals, molecularly imprinted polymer (MIP), carbon nanotubes (CNTs), and a wide range of potentially low-cost biosorbents, for PFASs removal from water or wastewater is critically reviewed. The evaluation and comparison of their PFASs sorption behavior in terms of kinetics and isotherms is presented. The mechanisms involved in PFASs adsorption processes, such as diffusion, electrostatic interaction, hydrophobic interaction, ion exchange and hydrogen bond, are discussed. The effects of the parameters variability on sorption process are highlighted. Based on the literature reviewed, a few recommendations for future research on PFASs adsorption are also elaborated.
Capsule: The adsorption behavior and mechanisms of perfluoroalkyl and polyfluoroalkyl substances (PFASs) on various adsorbents are reviewed.
Display omitted
•Resins and CNTs exhibit higher adsorption capacity than other adsorbents.•Biosorbents have great potential for efficient PFAS removal with cost-effectiveness.•Adsorption mechanisms involve electrostatic interaction, hydrophobic interaction and ion exchange.•The environmental parameters can influence PFASs adoption performance.
Objectives
To study the aggregation of multiple comorbidities in people with gout and explore differences in prognosis of gout flares among different subgroups.
Methods
Hierarchical clustering was ...performed to identify homogeneous subgroups among 2639 people with gout using eight comorbidities. A one-year follow-up of acute gout flares in 463 of these people was conducted; the incidence and the timing of gout flare
s
in each cluster were assessed to explore prognosis of gout flares. Binary logistic regression was applied to assess factors associated with gout flares.
Results
In baseline study, we identified five subgroups (C1–C5). C1 (
n
= 671, 25%) was characterized by isolated gout with few comorbidities. C2 (
n
= 258, 10%) were all obese. Almost all people in C3 (
n
= 335, 13%) had diabetes (99.7%). All people in C4 (
n
= 938, 36%) had dyslipidemia. C5 (
n
= 437, 17%) had the highest proportion of cardiovascular disease (CVD, 53%), chronic kidney disease (CKD, 56%), and cancer (7%). In follow-up study, C5 had the highest incidence (71.9%) and earliest onset (median 3 months) of gout flares. C2 had the lowest incidence (52.1%) and the latest onset (median 10 months) of gout flares. The highest relative risk for gout recurrent was seen for C5 (OR = 2.09). Other factors associated with the risk of gout flares were age at diagnosis of gout, duration of gout, presence of tophi, and smoking ≥ 20 cigarettes/day.
Conclusions
We clustered people with gout into five groups with varying comorbidities. People with CVD, CKD, and cancer had the highest risk of gout flares and should receive comprehensive care.
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