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In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night’s darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells. Extra-pineal MLT may have antioxidant and anti-inflammatory effects that dampen the innate immune response. These two seemingly divergent roles may be considered to be two sides of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effects of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility of integrating the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite of the fact that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

Abstract Background Diagnosis of a chronic illness, such as cancer may influence health behavior changes, such as smoking cessation. The present analyses examine associations between a cancer diagnosis (i.e., yes or no) and response to an opt‐out smoking cessation bedside intervention provided to hospitalized patients. It was hypothesized that patients with a past or present cancer diagnosis would report higher motivation and engagement with quitting smoking, and higher rates of smoking abstinence after hospital discharge, compared to those without a cancer diagnosis. Methods Chart review was conducted on 5287 inpatients who accepted bedside treatment from a counselor and opted‐in to automated follow‐up calls from July 2014 to December 2019. Results At the time of inpatient assessment, those with a past or present cancer diagnosis (n = 419, 7.9%) endorsed significantly higher levels of importance of quitting than those without a cancer diagnosis (3.92/5 vs. 3.77/5), and were more likely to receive smoking cessation medication upon discharge (17.9% vs. 13.3%). Follow‐up data from 30‐days post‐discharge showed those with a cancer diagnosis endorsed higher rates of self‐reported abstinence (20.5%) than those without a cancer diagnosis (10.3%; p

Abstract Background and Methods Hypergammaglobulinemia (hyper‐IgG) and hypogammaglobulinemia (hypo‐IgG) have been reported in patients with cystic fibrosis (CF). Although the clinical respiratory course is paradoxically different, depending on the IgG status, this association remains elusive. Therefore, we performed a longitudinal study to assess the annual evolution of IgG profiles in a cohort of pediatric patients with CF, from their diagnosis until 2016. We then compared clinical findings with the patients’ IgG status to determine whether IgG status could reflect the respiratory clinical course of patients with CF. Results Among the 66 patients with CF that were aged between 12 months and 18 years in 2016 (mean age: 9.3 years [SD: 5.2]), hypo‐IgG was observed in 15.2% and no hyper‐IgG was identified. Longitudinal assessment since diagnosis revealed no hyper‐IgG but 33.3% of patients had at least one sample showing hypo‐IgG, among which two patients displayed persistent hypo‐IgG. The number of pulmonary exacerbations, duration of antibiotic therapy, and erythrocyte sedimentation rate were all lower in hypo‐IgG patients. No difference was observed for the genotype, chronic Pseudomonas aeruginosa or Staphylococcus aureus infection, and in the parameters of lung function. Conclusion The IgG profile of pediatric patients with CF has changed over recent decades, particularly with regard to hyper‐IgG. In a significant portion of the pediatric CF population, hypo‐IgG is transient and only identifiable in longitudinal assessments. This study reinforces that hypo‐IgG patients paradoxically present a more favorable course of clinical status. Therefore, IgG levels could be a useful outcome marker in the follow‐up of patients with CF.

Hospital-based tobacco treatment programs provide tobacco cessation for a diverse array of admitted patients. Person-centered approaches to classifying subgroups of individuals within large datasets are useful for evaluating the characteristics of the sample. This study categorized patients who received tobacco treatment while hospitalized and determined whether demographics and smoking-related health conditions were associated with group membership. Chart review data was obtained from 4854 patients admitted to a large hospital in South Carolina, USA, from July 2014 through December 2019 who completed a tobacco treatment visit. Smoking characteristics obtained from the visit interview were dichotomized, and then latent class analysis (LCA) was conducted to categorize patients based on smoking history and interest in stopping smoking. Finally, logistic regressions were used to evaluate demographics and smoking-related health conditions as predictors of class membership. LCA generated 5 classes of patients, differentiated by heaviness of smoking and motivation to quit. Patients who were black/African American were more likely to be lighter smokers compared to white patients. Hospitalized patients with a history of hypertension, diabetes, and congestive heart failure were more likely to be motivated to quit and also were more likely to be lighter smokers at the time of hospitalization. Hospitalized patients who smoke and receive tobacco treatment are heterogeneous in terms of their smoking histories and motivation to quit. Understanding latent categories of patients provides insight for tailoring interventions and potentially improving tobacco treatment outcomes.

Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.

We previously reported successful classification of breast cancer versus benign tissue using the Cole relaxation frequency measured on tissue excised during breast surgery as part of a study at two urban hospitals in the U.S. Midwest. Using that health system’s cancer registry, we have discovered retrospectively that outcomes for patients who participated in the initial study can be classified correctly in 3 well-differentiated categories: nonrecurrent (NR); recurrent with no metastasis (RNM); and recurrent with metastasis (RM). As Cole relaxation frequency increases, the classification moves from NR to RNM and finally to RM. Multivariate analysis showed a significant association of “time-cancer-free” for all patients in these recurrent categories, with P-values ranging between 0.0001 to 0.0047. Thus, this follow-up report shows the potential feasibility of using Cole relaxation frequency as a prognostic parameter in a larger prospective study.

The purpose of this period prevalence study is to compare the prevalence of cardiovascular disease (CVD) in current/former established smokeless tobacco (SLT) users (ever SLT users who have used the product fairly regularly) to those who were: 1) never established cigarette smokers and SLT users, and 2) current/former established exclusive cigarette smokers (have smoked at least a 100 or more cigarettes in lifetime) only, adjusting for known risk factors for CVD. Analyses included 4,703 men ≥ 40 years of age who participated in the Population Assessment of Tobacco and Health (PATH) Study, Waves: 1–4, conducted between 2013 and 2017. Current users were those using SLT products daily or on some days, whereas former users had not used SLT and/or cigarettes in the past 12 months. CVD prevalence was defined as a self-reported diagnosis of congestive heart failure, stroke, or myocardial infarction. Among current/former established SLT users, years of use defined exposure history, while pack-years defined exposure history for smokers. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported with trend tests to examine dose–response associations. Current/former established exclusive SLT users were not significantly more likely to have had any CVD compared to never established cigarette and SLT users (OR = 1.7 [0.8–3.7]), or current/former established exclusive cigarette smokers (OR = 0.9 [0.5–1.8]). Current/former established exclusive cigarette smokers were more likely to have had any CVD compared to those who were never established cigarette and SLT users (OR = 1.6 [1.1–2.3]).

Background:. In response to the COVID-19 pandemic, new guidelines were issued cautioning against performing elective procedures. We aimed to assess the impact of the COVID-19 pandemic on operational and financial aspects of plastic surgery in Miami. Methods:. A multiple-choice and short-answer survey regarding practice changes and financial impact was sent to all 67 members of the Miami Society of Plastic Surgeons. Results:. A 41.8% (n = 28) response rate was obtained, five responses did not meet the inclusion criteria, and statistical analysis was performed on 34.3% (n = 23) of responses. Of the plastic surgeons who responded, 21.74% operate in an academic setting, 60.87% are in a single practitioner private practice, and 17.39% are in a multi-practitioner private practice. An estimated 60% of academic plastic surgeons had 75% or more of their previously scheduled cases canceled, compared with 57.14% in single practitioner private practice and 100% in multi-practitioner private practice. In total, 64.29% of single practitioner private practices and 50% of multi-practitioner private practices have had to obtain a small business loan. Single practitioner private practice plastic surgeons reported having an average of 6.5 months until having to file for bankruptcy or permanently close their practices, and multi-practitioner private practice plastic surgeons reported an average of 6 months. Conclusions:. Guidelines to support small business must be implemented in order to allow private practice surgeons to recover from the substantial economic impact caused by the pandemic because it is necessary to reestablish patient access and provide proper care to our patients.

Summary: The SARS-CoV-2 viral pandemic has induced a global health crisis, which requires more in-depth investigation into immunological responses to develop effective treatments and vaccines. To understand protective immunity against COVID-19, we screened over 60,000 asymptomatic individuals in the Southeastern United States for IgG antibody positivity against the viral Spike protein, and approximately 3% were positive. Of these 3%, individuals with the highest anti-S or anti-RBD IgG level showed a strong correlation with inhibition of ACE2 binding and cross-reactivity against non-SARS-CoV-2 coronavirus S-proteins. We also analyzed samples from 94 SARS-CoV-2 patients and compared them with those of asymptomatic individuals. SARS-CoV-2 symptomatic patients had decreased antibody responses, ACE2 binding inhibition, and antibody cross-reactivity. Our study shows that healthy individuals can mount robust immune responses against SARS-CoV-2 without symptoms. Furthermore, IgG antibody responses against S and RBD may correlate with high inhibition of ACE2 binding in individuals tested for SARS-CoV-2 infection or post vaccination.

BackgroundAfrican Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease.MethodsWe selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch.ResultsWe observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001).ConclusionsOverall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive (‘cold’) tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.

Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in a gene encoding a protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The CFTR protein is known to acts as a chloride (Cl−) channel expressed in the exocrine glands of several body systems where it also regulates other ion channels, including the epithelial sodium (Na+) channel (ENaC) that plays a key role in salt absorption. This function is crucial to the osmotic balance of the mucus and its viscosity. However, the pathophysiology of CF is more challenging than a mere dysregulation of epithelial ion transport, mainly resulting in impaired mucociliary clearance (MCC) with consecutive bronchiectasis and in exocrine pancreatic insufficiency. This review shows that the CFTR protein is not just a chloride channel. For a long time, research in CF has focused on abnormal Cl− and Na+ transport. Yet, the CFTR protein also regulates numerous other pathways, such as the transport of HCO3−, glutathione and thiocyanate, immune cells, and the metabolism of lipids. It influences the pH homeostasis of airway surface liquid and thus the MCC as well as innate immunity leading to chronic infection and inflammation, all of which are considered as key pathophysiological characteristics of CF.

Les dithiophosphates sont des additifs multifonctionnels utilisés de manière courante dans les lubrifiants moteur. On montre que les propriétés anti-usure et extrême pression qui nous intéressent ici sont étroitement liées aux caractéristiques physico-chimiques de la molécule. L'article fait le point des connaissances sur l'activité chimique des dithiophosphates (synthèse, analyse, décomposition thermique, réactivité vis-à-vis des surfaces métalliques). En conclusion, il est dressé un bilan sur les divers mécanismes proposés dans la littérature pour expliquer l'effet anti-usure de cette classe d'additifs. Dithiophosphates are multipurpose additives commonly used in engine lubricants. This article shows that the antiwear and extreme-pressure properties of interest to us here are closely linked to the physico-chemical properties of the molecule. The article goes on to review what is known about the chemical activity of dithiophosphates (synthesis, analysis, thermal decomposition, reactivity with metal surfaces). To conclude, a list is compiled of the different specific mechanisms mentioned in the literature to explain the antiwear effect of this category of additive.

Nous avons mis en oeuvre un test de frottement dans lequel les conditions tribologiques sont voisines de celles existant au niveau segment-chemise des moteurs à explosion. Nous avons éprouvé différentes huiles commerciales ainsi que des additifs purs. Ayant choisi la température comme paramètre variable au cours de ce test nous pouvons déterminer pour chaque lubrifiant une plage de température correspondant à une zone d'efficacité maximale de l'additif anti-usure qu'il contient. La température correspondant à la limite inférieure de cette plage est liée à la nature chimique de l'additif. De plus lorsqu'un gradient de température existe entre les deux pièces en frottement, on observe, dans la zone d'efficacité maximale du lubrifiant, un phénomène de pulsations verticales de la goutte d'huile placée dans le contact. Des éléments d'interprétation, expliquant ces deux phénomènes, sont proposés et conduisent à relier l'efficacité anti-usure d'un additif à ses propriétés d'adsorption à la surface des pièces frottantes. The tribological conditions in the test used were similar to these existing in the ringliner area. of explosion engines. Different commercial cils were tested along with pure additives. Since temperature was chosen as a variable parameter during these tests, it was possible to determine a temperature range for each lubricant, corresponding to the maximum efficiency zone for the antiwear additive it contained. The temperature corresponding to the lower limit of this range is linked to the chemical nature of the additive. Likewise, when a temperature gradient exists between two rubbing parts, a vertical pulsation phenomenon of the drop of cil n the contact area occurs in the maximum efficiency zone of the lubricant. Interpretation elements explaining these two phenomena are proposed and lead to linking the antiwear efficiency of an additive to its adsorption properties on the surface of rubbing parts.

Cet article a pour but de donner un aperçu des différentes méthodes les plus couramment utilisées dans l'étude des films monomoléculaires adsorbés sur un substrat massif et d'orienter l'utilisateur vers l'une ou l'autre de ces méthodes. Pour chacune d'elles, le fondement théorique, l'information fournie et la sensibilité de la mesure sont précisés. Une des difficultés réside dans le fait que les échantillons utilisés sont massifs et que les quantités adsorbées mises en jeu sont de ce fait toujours extrêmement petites. The aim of this article is to toke a look at the different methods most commonly used for analyzing the monomolecular films adsorbed on a massive substrate and to guide users toward one or another of these methods. For each of them, the theoretical validity, the information available and the measurement sensitivity are given. One of the difficulties lies in the fact that the samples used are massive and the adsorbed amounts involved are hence always extremely minute.

Objectives. This study reviewed the outcome of women attending a breast screening program recalled for assessment of microcalcifications and examined the incidence of a breast carcinoma detected during the following five years in any of the women who were given a benign diagnosis at assessment. Method. A retrospective study consisted of 235 clients attending an Australian BreastScreen program in 2003, who were recalled for investigation of microcalcifications detected on screening mammography. Records for the following five years were available for 168 women in the benign outcome group including those who did not require biopsy at initial assessment. Results. Malignant disease was detected in 26.0% (n=146) of the women who underwent biopsy. None of the women in the benign outcome group, with available five-year follow-up records, developed a subsequent breast cancer, arising from the calcifications initially recalled in 2003. Conclusions. This study highlights the effectiveness of an Australian screening program in diagnosing malignancy in women with screen detected microcalcification. This has been achieved by correctly determining 38% (n=235) of the women as benign without the need for biopsy or early recall. A low rate of open surgical biopsies was performed with no cancer diagnoses missed at the time of initial assessment.

Background: Genetic and environmental factors have been shown to contribute to the development of congenital heart disease (CHD). To date, the focus of scientific articles has primarily centered on genetics and maternal environmental factors, with comparatively less attention given to paternal risk factors. Objectives: This study aims to investigate the potential association between paternal pre‐conceptional physical activity levels (PA), along with paternal peri‐conceptional smoking and alcohol consumption, and the risk of CHD in offspring. Materials and methods: An observational case–control study was conducted in Lebanon, with 279 participants, aiming to investigate potential risk factors for CHD. We included children with confirmed CHD, born between 2012 and 2022. Controls born in the same timeframe were selected randomly from the general population using online questionnaire forms. Mean age of children included was 6 years old (0–10). The pre‐conceptional PA was assessed using the Global Physical Activity Questionnaire validated in Arabic. In addition, paternal smoking, alcohol consumption, and maternal risk factors were collected. Results: The study included 128 CHD cases (45.9%) and their parents, as well as 151 healthy infants (54.1%) and their parents. There were no statistically significant variations in the alcohol consumption noted between the fathers in the case and control groups (p = 0.18). The paternal involvement in recreational‐related PA during the peri‐conception period was associated with a reduced risk of the CHD development in offspring by 46.9% (OR = 0.531, 95% CI: 0.301–0.936, p = 0.029). Additionally, increasing paternal total sitting time by 1 h above the average, which was approximately 260 min (4 h), increased the risk of CHD in offspring by 0.4% (p = 0.001). Moreover, paternal smoking exhibited an apparent association with a 56% increased risk of offspring developing CHD, notwithstanding that the confidence intervals included the null (OR = 1.56, 95% CI: 0.86–2.8, p = 0.136). Discussion and conclusion: This observational study is the first to report a potential association between paternal PA, and CHD in offspring. This study aligns with previous reports, advocating for the paternal engagement in PA and the adoption of healthy lifestyle habits, especially during the critical stages of conception. Such practices are strongly recommended to enhance fertility and promote optimal health for offspring. However, due to the subjectivity in reporting PA and lack of molecular proof, additional prospective and molecular studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Double polymer networks (DNs) consist of two interpenetrating polymer networks and can offer properties that are not merely a sum of the parts. Here, we report an elastic DN made from two supramolecular polymers (SMPs) that consist of the same poly(n‐butyl acrylate) (BA) backbone. The two polymers feature different non‐covalent binding motifs, which form dynamic, reversible cross‐links. The polymers were prepared by reversible addition−fragmentation chain‐transfer polymerization of n‐butyl acrylate and either the self‐complementary hydrogen‐bonding motif 2‐ureido‐4[1H]pyrimidinone, or the 2,6‐bis(1′‐methylbenzimidazolyl)pyridine ligand, which forms complexes with metal ions. The supramolecular DN made by these components combines features of the single networks, including high thermal stability and resistance to creep. The DN further exhibits excellent healability and displays a higher extensibility and a higher toughness than its constituents. The mechanical characteristics of the DN can be further enhanced by selectively pre‐stretching one of the networks, which is readily possible due to the reversible formation of the supramolecular cross‐links and their orthogonal stimuli‐responsiveness. [ABSTRACT FROM AUTHOR]

The pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. The main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the night darkness hours. We have recently reported that melatonin exerts important immuno regulatory functions. Here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. This effect seems to be mediated by antigen-activated T cells via an opiatergic mechanism.