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1.
Context: Atopic dermatitis (AD) is a chronic, inflammatory, itching skin disorder, which may worsen due to stress, depression and anxiety. Tachykinins may be involved in inflammation signaling as well as they may have a role in stress, depression and anxiety.

Objective: This study aimed to measure the expression of tachykinin markers, in the skin of patients with AD, and the correlation of these tachykinins with clinical and psychodemographic parameters.

Materials and methods: Twenty-eight adult patients with AD were investigated regarding tachykinin expression in skin biopsies, using an immunohistochemical technique. The patients were characterized with clinical and psychodemographic parameters.

Results: The number of substance P and neurokinin (NK)A positive nerve fibers, as well as NKA positive mononuclear dermal cells, was increased in lesional compared to non-lesional skin. Interestingly, the depression score and the number of dermal NK-1 receptor (R) positive cells in lesional as well as in non-lesional skin showed a correlation.

Conclusion: These findings indicate an upregulation of the tachykinergic system in the inflamed skin of AD.  相似文献   


2.
Background: Despite the progress in HIV care, adherence to follow up remains critical. Disengagement impairs the benefit of HIV care and the increasing number of data that associates failed retention with worse outcomes has led public health institutions to consider retention in care as a new tool to fight against HIV pandemic.

Objective: The aim of this retrospective, observational study was to estimate the burden of disengagement and reengagement in care in our HIV cohort and to identify the characteristics of our LTFU and reengaged patients. Moreover, we build our cascade of care to explore how closely our center aligned with the “90–90–90” targets.

Methods: From the local electronic database we extracted all HIV-infected patients with at least one contact with HIV Clinic between 2012 and 2018 excluding deceased and transferred patients.

Our definition of LTFU was based on the lack of any visit during at least 1 year after the last visit. Patients re-engaged were defined as those firstly considered as LTFU patients who subsequently were newly linked to HIV care.

Results: About 8% of patients were lost to follow up during the period of study, with a rate of less than 2% per year and 14.1% of them were re-engaged in care. The cascade of care shows, among HIV cases diagnosed between 2011 and 2018, 86.7% patients retained in care, 94.1% of whom were on cART and 95.6% of whom were virologically suppressed.

A higher attrition was found among infections diagnosed since 2011 than before 2011, such as women, patients coming from foreign countries and those with poor virological control.

Conclusions: The retention rate found in our cohort is high and is in accordance with the 90–90–90 strategy. Nevertheless, understanding disengagement and re-engagement determinants is important to strengthen retention in care in the most fragile population.  相似文献   


3.
Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5?years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations.

GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice.

Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted.

Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines.

Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally.

Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.  相似文献   


4.
Objective: To replicate previous research on Conners’ Continuous Performance Test – Second Edition subscales as performance validity tests (PVTs) in children.

Method: Classification accuracy for the Omissions (OMI), Hit Reaction Time (HRT), and Perseverations (PER) subscales was computed for 414 children and adolescents.

Results: Overall, OMI, HRT, and PER demonstrated good specificity but low and variable sensitivity across cutoffs.

Conclusions: Results suggest that OMI, HRT, and PER can function as embedded PVTs in mixed clinical samples of children, although their clinical utility is limited by their low sensitivity. Implications for the use of these PVTs in the context of attention-deficit/hyperactivity disorder evaluations, medication-seeking patients, and sports concussion clinics are discussed.  相似文献   


5.
Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.

Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.

Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.

Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.

Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.  相似文献   


6.
Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes.

Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders.

Subjects and methods: Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6?years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12?months) and height (2 and 3?years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC.

Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC.

Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.  相似文献   


7.
Background/aim: T-cell immunotherapies are rapidly gaining grounds in clinical success. Presently, there is first-to-market knowledge on the translation of research scale methods to clinical and commercial scales. Improved understanding can lead to more consistent and efficient production, scaling, and eventual potency. T-cell checkpoint markers, proliferation, and T-cell cluster size and disaggregation are one set of parameters that have yet to be explored.

Methods: We herein activated T-cells and assessed various mechanical dissociation frequencies in relation to expression of checkpoint markers (measured by flow cytometry).

Results: We herein find increased T-cell proliferation capacity with increased dissociation frequency. We also find that with increased cluster size and duration, lower proliferation, and increased expression of checkpoint markers.

Conclusions: These findings reveal new translation findings with respect to T-cell handling and production and suggest that T-cell disaggregation may be important to improved cell yields and phenotype.  相似文献   


8.
Background: Growth in tibia length is considered to be particularly sensitive to environmental stress.

Aim: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children.

Subjects and methods: Data included a nationwide random sample of 17,155 schoolchildren, 7–18?years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio.

Results: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio.

Conclusion: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children.  相似文献   


9.
Background: Family socioeconomic status (SES) is related to a child’s educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence.

Aim: To study whether family SES affects a child’s adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence.

Subjects and methods: Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n?=?37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29–43?years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used.

Results: Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model.

Conclusions: The results show that family SES affects the child’s adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.  相似文献   


10.
Background: Serbs mainly live in the territory of the recently re-established state of Serbia. However, the turbulent history in the Balkan Peninsula has led to settlement of Serbs not only within present day Serbia, but also in different parts of neighbouring countries.

Aim: To define polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci in a modern Serbian population from the central part of the Balkan Peninsula.

Subjects and methods: The reference sample consisted of 303 men declared as Serbs over three generations. Localities of the collected materials include the territories of Serbia, Bosnia and Herzegovina, Croatia and Montenegro. DNA samples were typed using the PowerPlex®Y23 amplification kit.

Results: The highest locus diversity was observed for DYS385 and DYS481. In this study the most abundant haplogroups were I2a, E1b1b, R1a and I1. The largest genetic distances between the Serbs and other close Southern Slavs were for the Macedonians and Slovenians.

Conclusion: This study is the first one to define STR polymorphism of Serbian people not only from Serbia but also from other parts of the Balkan Peninsula. The presented genetic data may be useful in further examinations of the genesis and genetic structuring of the present-day Serbian gene pool.  相似文献   


11.
Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown.

Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole.

Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120?μg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris® and LAZAR® programs).

Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30?μg/mL) and 6?μg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays.

Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.  相似文献   


12.
Context: Prevalence of bronchial asthma massively increases worldwide, while the frequent therapies are still not sufficient. Polydatin, a naturally occurring glycoside, was known as to have anti-inflammatory and anti-oxidant effects.

Objective: The current study aimed to investigate the possible protective effect of polydatin against experimental bronchial asthma in rats.

Material and methods: Bronchial asthma was induced by ovalbumin (OVA) sensitization and challenge. Rats were randomly allocated into five groups; Group I (normal control group); Group II (asthma control group) received OVA; Group III (reference standard treatment group) received dexamethasone (1?mg/kg/day); Group IV (treatment group) received polydatin (200/mg/kg); and Group V (polydatin control group). The inflammatory biomarkers interleukin-4 (IL-4), IL-5, IL-13, tumor necrosis factor-alpha, interferon-gamma and absolute eosinophil count in bronchoalveolar lavage fluid (BALF), as well as serum immunoglobulin E were assessed, coupled with the oxido-nitrative stress biomarkers malondialdehyde and glutathione reduced levels and superoxide dismutase activity in the lung tissue, besides inducible nitric oxide synthase level in BALF. Western blot analysis of surfactant-D and immunohistochemical assay of urocortin (UCN) expression in the lung was performed.

Results: Polydatin significantly reduced the inflammatory mediators and restored the normal values of oxidative and nitrosative stress biomarkers. It also significantly reduced the expression of surfactant-D and UCN as compared to asthma control. The histopathological study strongly augmented the biochemical results.

Discussion and conclusions: Polydatin may be a promising protective agent against experimentally induced bronchial asthma. Modulation of SP-D and UCN expressions seems to mediate such protective effects.  相似文献   


13.
Background: This study was conducted to compare the levels of maternal serum soluble endoglin (sEng) and cell-free fetal DNA (cffDNA) in pregnant females with PE to normotensive pregnant ones, together with relating these levels to preeclampsia (PE) severity and onset.

Method of the study: It was a comparative study in Mansoura University Hospital, Egypt, to detect the levels of serum sEng by ELISA besides the levels of cffDNA by quantitative real-time polymerase chain reaction in 80 pregnant females suffering from PE in addition to 80 normotensive pregnant ones that were included as control.

Results: Levels of serum sEng and cffDNA were higher in PE cases than control (p < 0.0001? both) and were significantly related to the severity of the disease. Levels were also higher in early than late onset PE (p < 0.003? and <0.002?, respectively). Sensitivities, specificities, positive, and negative predictive values in addition to accuracy of serum sEng and cffDNA were 97.5%, 98.8%, 98.7%, 97.5%, and 98.1% and 97.5%, 93.8%, 94.0%, 97.4%, and 95.6%, respectively.

Conclusion: Maternal serum sEng and cffDNA can be good markers for diagnosis of PE in Egyptian patients. They are positively related to the disease severity.

Abbreviations: cffDNA; Cell-Free Fetal DNA, sEng; soluble Endoglin, PE; preeclampsia, qRT PCR; Quantitative real-time polymerase chain reaction.  相似文献   


14.
Context: Pyocyanin is a typical Pseudomonas aeruginosa virulence factor, a common Gram-negative rod responsible for a wide range of severe nosocomial infections. There is evidence indicating that pyocyanin has multiple biological activities, but little is known about anti-inflammatory properties.

Objective: This study investigated pyocyanin effect on nitric oxide and cytokine production in lipopolysaccharide (LPS)-activated murine peritoneal macrophages.

Materials and methods: Macrophages were incubated in the presence and absence of pyocyanin (1, 5, 10, 50, and 100 µM) with and without LPS (1 µg/mL). Nitric oxide production was determined by Griess reagent and tumor necrosis factor (TNF)-α and interleukin (IL)-1β production was assessed by enzyme-linked immunosorbent assay. In addition, pyocyanin effects on zymosan A-induced peritonitis in mice were evaluated.

Results: Pyocyanin (5 and 10 µM) decreased nitric oxide, TNF-α, and IL-1β production independent of macrophage death. On the other hand, in vivo, pyocyanin (5 mg/kg) was not able to affect leukocyte migration into the site of inflammation.

Discussion and conclusion: Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless more detailed studies should be performed to confirm this hypothesis.  相似文献   


15.
Context: Humans constantly respond to environmental stressors challenging their somatic stability. Allostasis, an evolved neuroendocrine/physiological stressor response system, is our main pathway for doing so. Effective allostasis returns somatic systems to their current optima; over a lifetime of stressor responses, related systems fail, effectiveness declines, and physiological dysregulation (i.e. allostatic load) increases. Global Climate Change (GCC) multiplies environmental stressors on human populations and is likely to increase allostatic load.

Objectives: As a population-level stressor, GCC increases risks for multiple stressors, including sociocultural instability and food and water insecurity, while also motivating migration. We predict GCC increases risk for elevated allostatic load. Here, we review pathways by which GCC increases climatic and social stressors contributing to greater stress and allostatic load.

Methods: Based upon published sources and primary ethnographic case studies, this review examines how GCC, by multiplying climate-related stressors, likely increases social instability, food and water insecurity, and migration. Thereby, it is proposed that GCC contributes to allostatic load.

Results: GCC multiplies stressors on local populations. Those experiencing social insecurity related to GCC during growth and development are expected to show the largest influences on their lifetime allostatic load. Similarly, as GCC increases food and water insecurity, it likely will increase allostatic load in those affected and is likely to propel migrants to seek improved living circumstances. These stressors may be continued among their descendants via historical trauma or epigenetic responses.

Conclusion: GCC accentuates effects of environmental and sociocultural stressors on human populations. Those exposed to GCC are likely to show lifelong elevated allostatic load.  相似文献   


16.
Introduction: The Wechsler Memory Scale (WMS) is a standardised battery for assessing memory functions. We aimed to investigate the relationship between all WMS scores, including subtests, and whole-brain structure in a relatively large sample.

Methods: Participants were 93 patients with schizophrenia and 117 healthy individuals, all right-handed and of Japanese ethnicity, and matched for age and sex. Their memory functions were assessed using the WMS-Revised (WMS-R). Their grey and white matter structure was analyzed using voxel-based morphometry and diffusion tensor imaging.

Results: Verbal memory score correlated positively with volumes of the left parahippocampal gyrus and hippocampus, while general memory score correlated positively with volumes of the left parahippocampal and fusiform gyri and hippocampus (p?<?0.05, corrected), while there was no correlation with white matter fractional anisotropy values in healthy individuals. No correlation was observed between any WMS-R score and grey or white matter structure in patients.

Conclusions: Using whole-brain structural magnetic resonance imaging, we found several significant correlations between WMS-R scores and grey matter volume in the brains of healthy individuals, while no correlation was found in those of patients with schizophrenia.  相似文献   


17.
Background: Adipocytokines have been implied to be involved in multiple sclerosis (MS) pathogenesis. MS patients whose first clinical episode is optic neuritis (ON) have been reported to display a milder disease course. In this study, we aimed to show whether this milder disease course is related to reduced adipokine production.

Methods: A total of 55 (24 with ON as the first clinical episode) relapsing-remitting MS (RRMS) patients and 40 healthy individuals were recruited. Concentrations of adipokines were measured in sera by ELISA.

Results: The levels of adiponectin, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1) and IL-8 were significantly higher in RRMS patients compared with healthy controls. RRMS cases starting with ON had lower expanded disability status scale scores. Serum adiponectin, leptin, resistin and MCP-1 levels were significantly lower in MS patients, whose first clinical episode was ON.

Conclusions: MS patients with ON as the first manifestation display both lower disability scores and reduced serum adipokine levels implying that adipocytokine production is associated with MS progression. Exact mechanisms of this association in MS patients with first episode ON need to be further studied.  相似文献   


18.
Introduction: Chronic autoimmune diseases affect 5–10% of the population worldwide and are largely predominant in women. Sex hormone changes have been widely investigated based on changes in the clinical phenotypes observed during pregnancy and menopause.

It is known that females with autoimmune diseases manifest a higher rate of circulating leukocytes with a single X chromosome, and there have been several reports on the role of X chromosome gene dosage through inactivation or duplication in autoimmunity. However, it is also important not to overlook men with autoimmune diseases, who might manifest a more frequent loss of the Y chromosome in circulating leukocytes.

Areas covered: In the present review, we will discuss the current evidence supporting the mechanisms of female predominance in rheumatic diseases, by discussing the role of reproductive history, sex hormones and abnormalities related to them, clinical differences between male and female patients, and epigenetic changes that have been evaluated through twin studies on genetic and environmental changes in rheumatic patients.

Expert opinion: The influence of sex hormones and chromosomes on the function of the innate and adaptive immune systems needs to be clarified, to better understand the risk of autoimmune diseases, early diagnostic tools, and therapeutic response.  相似文献   


19.
Introduction: Smoking is the single most important cause of preventable mortality worldwide. Besides being associated with major cardiovascular and bronchopulmonary diseases, and several cancers, it has been linked with a number of immune-related conditions, including psoriasis and psoriatic arthritis (PsA)

We aimed to summarize data on the role of smoking in the development and prognosis of psoriasis and PsA, pointing to the consequences in terms of disease management.

Areas covered: Mechanisms, clinical manifestations, and comorbidities associated with smoking in psoriasis and PsA were reviewed by searching Medline, Embase and Cochrane Library databases for papers published between January 2000 and July 2018 using combination of terms. Articles not written in English were excluded.

Expert commentary: Smoking is a risk factor for psoriasis development. As for PsA, smoking is positively associated with the disease at the population level, but it is negatively associated in patients with psoriasis. This phenomenon is referred to as the ‘smoking paradox’ of PsA. Smoking may cause poor response and reduced adherence to treatment of both psorasis and PsA. Physicians need to be aware of the smoking habits of their patients with psoriasis and PsA; whenever possible, smoking cessation programs should be considered.  相似文献   


20.
Introduction: Although considered a promising design for testing social cognition, it is not clear to what extent the EmoBio test of emotion recognition actually predicts community functioning. It is also not clear whether the test measures something unique or different from nonsocial cognition. The present study tests whether EmoBio accounts for GAF function score and two operationalised community outcome measures. The study also analyses cognitive predictors of EmoBio performance, testing whether stimulus modality affects prediction.

Methods: Eighty-three patients with schizophrenia were tested with EmoBio, the cognitive battery MCCB and WAIS-IV.

Results: EmoBio accounted for a significant portion of variance in all three outcome measures. Only EmoBio predicted Lifetime Relationship status, and EmoBio remained a significant predictor of Independent living beyond non-social cognition. All cognitive measures contributed significantly to the variance in EmoBio, but entered together explained only a third of total variance.

Conclusion: The study shows that emotion recognition accounts for community outcome. There was no clear effect of test-modality in predicting EmoBio performance, indicating no method invariance problem with EmoBio. It also indicates that the mechanisms underlying impaired social cognition in schizophrenia are different from the hypothesised non-verbal learning deficits in the disorder.  相似文献   


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