Immunological and respiratory changes in tobacco workers

BACKGROUND: Tobacco workers develop respiratory changes following occupational exposure to tobacco dust. METHODS: This study investigated 102 tobacco workers as well as a group of 30 matched control workers. Immunological testing, symptom questionnaire, and lung function measurements were performed in all workers. RESULTS: Increased total IgE was found in 12.7% of tobacco workers but in none of the controls (P < 0.05). Increased specific IgE (tobacco allergen) was recorded in 26.7% of tobacco workers with positive skin tests to tobacco extract but in none of the controls (P < 0.05). Regression analysis of ventilatory tests in female tobacco workers indicated a significant association of FEF75 to employment and smoking among workers with positive skin tests to tobacco. There were, however, no other associations between positive immunologic findings and lung function abnormalities and symptoms. CONCLUSIONS: Our study found increased immunological reactions in the tobacco workers. However, with the possible exception of lung function at low lung volume in female workers, these reactions do not appear to contribute significantly to the symptoms and lung function abnormalities seen in these workers. Am. J. Ind. Med. 45:76-83, 2004.     

Gastrointestinal complications in treatment with classical nonsteroidal antirheumatic agents

The most frequent gastro-intestinal complications in classical NSAID treatment are presented. Nausea and dispepsy are present in 60 percent, and gastric erosions in 50 percent of patients on regular NSAID treatment. COX-2 inhibitors with lower rate of gastro-intestinal complications are mentioned.     

A randomized,placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women

Objective: To characterize the chronology of hemodynamic changes in in vitro fertilization (IVF) cycles and its relationship with circulating ovarian steroids, cytokines, and their mediator nitric oxide.

Design: Prospective, cross-sectional study.

Setting: University teaching hospital.

Patient(s): Eighty-eight IVF patients.

Intervention(s): Ovarian stimulation with FSH under pituitary suppression.

Main Outcome Measure(s): Circulating levels of estradiol, progesterone, nitrite/nitrate, interleukin-6, vascular endothelial growth factor, tumor necrosis factor , aldosterone, norepinephrine, as well as measurements of plasma renin activity and mean arterial pressure.

Result(s): The maximal stimulation of the renin-aldosterone and sympathetic nervous systems was seen 7 days after hCG administration, although values still remained elevated over normal control values on day of hCG + 11. Mean arterial pressure in IVF patients remained significantly reduced throughout the luteal phase. Changes in the stimulation of the renin-aldosterone system correlated temporally with progesterone but not estradiol levels. No significant changes were observed in circulating concentrations of cytokines investigated or nitric oxide.

Conclusion(s): The circulatory changes and the homeostatic activation of the renin-aldosterone system and sympathetic nervous system that consistently develop in patients undergoing controlled ovarian hyperstimulation for IVF is a feature associated with the luteinization process. These hemodynamic changes occur in the absence of variations in the circulating levels of cytokines potentially involved in ovarian hyperstimulation syndrome.     

Primary sclerosing cholangitis--diagnosis and therapy

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin, characterized by inflammation, fibrosis, and obliteration of bile ducts, which ultimately results in biliary cirrhosis. The condition most commonly affects intrahepatic and extrahepatic bile ducts together, but sometimes only intrahepatic or extrahepatic ducts are involved. PSC is often associated with inflammatory bowel disease, especially ulcerative colitis. The majority of patients are initially asymptomatic, and identified on the basis of elevated serum levels of alkaline phosphatase or gamma-glutamyl transpeptidase, especially while screening patients with ulcerative colitis. Diagnosis is based on characteristic cholangiographic appearance with focal bile duct dilatations proximal to areas of stricturing that produce a beaded appearance. Ursodeoxycholic acid is most effective medical therapy, with other symptomatic measures, while liver transplantation is the treatment of choice for patients with advanced liver disease.     

Heavy metal concentrations in ground beetles, leaf litter, and soil of a forest ecosystem

The objective of this study was to quantify the relationships between heavy metal concentrations in soil, leaf litter, and ground beetles at four sampling sites of a forest ecosystem in Medvednica Nature Park, Croatia. Ground beetles were sampled by pitfall trapping. Specimens were dry-ashed and soil and beetle samples digested with nitric acid. Lead, cadmium, copper, zinc, manganese, and iron were analyzed using atomic absorption spectrometry. Statistically significant differences between plots were found for lead, cadmium, and iron in ground beetles. Correlations between ground beetles and soil or leaf litter were positive for lead and cadmium concentrations and negative for iron concentration. Differences in species metal concentrations were recorded. Higher concentrations of all studied metals were found in female beetles. However, a significant difference between sexes was found only for manganese. Significant differences in species metal concentrations were found for species that differ in feeding strategies and age based on breeding season and emergence of young adults.     

Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group

Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h²) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444–4458, 2017. © 2017 Wiley Periodicals, Inc.     

Modular-Level Functional Connectome Alterations in Individuals With Hallucinations Across the Psychosis Continuum

Functional connectome alterations, including modular network organization, have been related to the experience of hallucinations. It remains to be determined whether individuals with hallucinations across the psychosis continuum exhibit similar alterations in modular brain network organization. This study assessed functional connectivity matrices of 465 individuals with and without hallucinations, including patients with schizophrenia and bipolar disorder, nonclinical individuals with hallucinations, and healthy controls. Modular brain network organization was examined at different scales of network resolution, including (1) global modularity measured as Q_max and Normalised Mutual Information (NMI) scores, and (2) within- and between-module connectivity. Global modular organization was not significantly altered across groups. However, alterations in within- and between-module connectivity were observed for higher-order cognitive (e.g., central-executive salience, memory, default mode), and sensory modules in patients with schizophrenia and nonclinical individuals with hallucinations relative to controls. Dissimilar patterns of altered within- and between-module connectivity were found bipolar disorder patients with hallucinations relative to controls, including the visual, default mode, and memory network, while connectivity patterns between visual, salience, and cognitive control modules were unaltered. Bipolar disorder patients without hallucinations did not show significant alterations relative to controls. This study provides evidence for alterations in the modular organization of the functional connectome in individuals prone to hallucinations, with schizophrenia patients and nonclinical individuals showing similar alterations in sensory and higher-order cognitive modules. Other higher-order cognitive modules were found to relate to hallucinations in bipolar disorder patients, suggesting differential neural mechanisms may underlie hallucinations across the psychosis continuum.     

Medicinal signaling cells niche in stromal vascular fraction from lipoaspirate and microfragmented counterpart

AimTo expand our previous findings by increasing the number of patients in a study characterizing medicinal signaling cells (MSC) of stromal vascular fraction from lipoaspirate (SVF-LA) and from microfragmented lipoaspirate (SVF-MLA) applied for the treatment of osteoarthritis (OA).MethodsTwenty OA patients, including 8 new patients, acquiring autologous microfragmented adipose tissue were enrolled. In-parallel immunophenotyping of SVF-LA and SVF-MLA was performed. The samples were incubated in a DuraClone SC prototype tube targeting the CD31, CD34, CD45, CD73, CD90, CD105, and CD146 surface markers, stained with the DRAQ7 cell nuclear dye and Live/Dead Yellow Fixable Stain, and analyzed by flow cytometry.ResultsThe population phenotypes in SVF-LA and SVF-MLA samples included CD31⁺CD34⁺CD73^±CD90^±CD105^±CD146^± endothelial progenitors (EP), CD31⁺CD34^-CD73^±CD90^±CD105^-CD146^± mature endothelial cells, CD31^-CD34^-CD73^±CD90⁺CD105^-CD146⁺ pericytes, CD31^-CD34⁺CD73^±CD90⁺CD105^-CD146⁺ transitional pericytes, and CD31^-CD34⁺CD73^highCD90⁺CD105^-CD146^- supra-adventitial-adipose stromal cells. Compared with the autologous SVF-LA samples, the prevailing cell type in SVF-MLA were EP, which outnumbered leukocytes and supra-adventitial-adipose stromal cells (SA-ASC). The ratio of progenitor cells in SVF-MLA samples differed between female and male patients, showing a higher EP-pericyte and pericyte-SA-ASC ratio in men.ConclusionOur results, hallmarked by EP-enriched anti-inflammatory features and indicating a possible sex-specific impact, contribute to defining the cellular composition of the clinically applied MSC serving as a regenerative cell therapy in OA.

Mesenchymal stromal/stem cells (MSC) are well known for their capability of differentiating into mesenchymal cell types. Caplan has recently suggested that they are renamed into medicinal signaling cells with the same acronym (1). The name ought to be adapted as our knowledge of the biological concept has expanded: during tissue regeneration, MSC perform their function via signaling rather by than differentiating – as they do under cell culture conditions (2-4). MSC comprise a heterogeneous population of stromal and stem cells with additional immunosuppressive and trophic properties, which upon injury or inflammation modulate the local environment by secreting numerous anti-apoptotic, anti-scaring, angiogenic, and mitotic factors (1,5). This paradigm for tissue regeneration has been brought up by the studies of MSC in osteoarthritis (OA), the most common joint disorder (6). MSC from adipose tissue are now widely investigated as a novel therapeutic method in the treatment of OA (7).Although 20 years have passed since the first characterization of the multipotent MSC from adult adipose tissue, ie lipoaspirate (3), a complete characterization of this heterogeneous cell type remains elusive. This tremendous discovery opened up unprecedented possibilities in clinical application, however, undefined cellular heterogeneity and non-standardized protocols represent the main obstacle to the MSC usage in regenerative medicine. Together with other cell types, MSC are found in the stromal vascular fraction (SVF), which is obtained from adipose tissue upon collagenase treatment. Besides being a fruitful source of MSC, adipose tissue seems to potentiate the MSC-mediated tissue regeneration if it previously undergoes microfragmentation. The secretome of microfragmented adipose tissue more abundantly harbors cytokines and angiogenic factors, accompanied by immunomodulation, angiogenesis, and tissue reparation benefits (8). In this new light of paracrine activity of microfragmented adipose tissue, the Lipogems® device brings innovative technology for processing autologous adipose tissue, producing small intact clusters of perivascular microfragments with a high therapeutic potential (9,10). In a prospective non-randomized study, an intra-articular injection of such a product led to a successful outcome, as revealed by an increased glycosaminoglycan content in the hyaline cartilage of the knee joint (11,12). Several studies of knee OA treatment demonstrated the efficacy of adipose MSC in tissue repair, and even a low-dose MSC application yielded significant functional improvement with pain relief (13-15).Although clinical implementation of microfragmented adipose tissue has brought an impressive step forward in orthopedics, standardization of clinical application requires a better understanding of MSC heterogeneity and the cellular subset characterization. The flow cytometry analysis of human lipoaspirate has shown that a heterogeneous SVF mixture contains endothelial progenitor (EP) cells (CD31⁺CD34⁺CD146⁺), endothelial mature (EM) cells (CD31⁺CD34^-CD146^±), pericytes (CD31^-CD34^-CD146⁺), supra-adventitial-adipose stromal cells (SA-ASC) (CD31^-CD34⁺CD146^-), and transitional pericytes (TP) (CD31^-CD34⁺CD146⁺), with differential expression of the CD73, CD90, and CD105 mesenchymal markers (16,17). The aim of this study was to expand the number of patients from our previous immunophenotyping analysis of SVF from lipoaspirate (SVF-LA) or microfragmented lipoaspirate (SVF-MLA) by means of polychromatic flow cytometry (18). Since SVF-MLA is used therapeutically in OA patients, the results contribute to the biological understanding of the cartilage regeneration.