The longitudinal effects of social support and hostility on depressive tendencies

This 14-year longitudinal study examined the independent association between perceived social support and the 5-year progression of depressive tendencies while taking into account the potential effects of childhood/adolescent anger and later hostility. From the on-going population based study of "Cardiovascular Risk in Young Finns", 553 male and 860 female participants responded to a revised version of Beck's Depression Inventory in 1992 and 1997. Hostility and perceived social support were assessed by self-rated questionnaires in 1992. Childhood/adolescent anger was assessed by parent-reports in 1983. Our results showed that higher levels of perceived social support were associated with the decrease of depressive tendencies after 5 years and lower levels of depressive tendencies prospectively and after 5 years. This association persisted after adjusting for childhood/adolescent anger and later hostility. In addition, hostility was strongly related to the 5-year increase of depressive tendencies and higher levels of depressive tendencies. Social support may therefore be a long-term protective factor from depression irrespective of personality characteristics, such as hostility and anger.     

Impact of DNA amplification on gene expression patterns in breast cancer

Genetic changes underlie tumor progression and may lead to cancer-specific expression of critical genes. Over 1100 publications have described the use of comparative genomic hybridization (CGH) to analyze the pattern of copy number alterations in cancer, but very few of the genes affected are known. Here, we performed high-resolution CGH analysis on cDNA microarrays in breast cancer and directly compared copy number and mRNA expression levels of 13,824 genes to quantitate the impact of genomic changes on gene expression. We identified and mapped the boundaries of 24 independent amplicons, ranging in size from 0.2 to 12 Mb. Throughout the genome, both high- and low-level copy number changes had a substantial impact on gene expression, with 44% of the highly amplified genes showing overexpression and 10.5% of the highly overexpressed genes being amplified. Statistical analysis with random permutation tests identified 270 genes whose expression levels across 14 samples were systematically attributable to gene amplification. These included most previously described amplified genes in breast cancer and many novel targets for genomic alterations, including the HOXB7 gene, the presence of which in a novel amplicon at 17q21.3 was validated in 10.2% of primary breast cancers and associated with poor patient prognosis. In conclusion, CGH on cDNA microarrays revealed hundreds of novel genes whose overexpression is attributable to gene amplification. These genes may provide insights to the clonal evolution and progression of breast cancer and highlight promising therapeutic targets.     

Stapes surgery: a 32-year follow-up

Despite a widespread use of stapes surgery, little is known about the long-term durability of hearing results. The present study provides data over a long time frame (32 years) on hearing changes following surgical treatment. During a 10-year period (1965-1975) stapes surgery was performed in 322 consecutive patients in Tampere University Hospital, Finland. Postoperative evaluation was performed in the same hospital during the years 2001 and 2002 in 58 patients (41 females, 17 males). Of these 58 patients, 68 ears were operated decades ago (stapedoplasty in 67 ears and stapes mobilization in one ear). The mean follow-up time at the latest visit was 32.9 years. At the long-term follow-up, we found that the operative result was very well maintained: 37% of the patients had air-bone gap closure less than 10 dB. Most of the patients (83%) reached postoperative (6-12 months) air-bone gap closure less than 20 dB. The result was maintained by 75% of the patients. Stapes surgery gives a rise to a better social life for the hearing-impaired patient and delays the need for hearing aid in most patients.     

Neuron navigator 3 alterations in nervous system tumors associate with tumor malignancy grade and prognosis

Copy number changes or reduced expression of the Neuron navigator 3 (NAV3) gene occurs in neuroblastomas and malignancies of epithelial or lymphoid origin. To elucidate whether NAV3 has a role in the tumorigenesis of nervous system tumors in general, we studied central and peripheral nervous system tumors for NAV3 copy number changes. In search for common tumorigenic denominators, we analyzed 113 central and peripheral nervous system tumors, including glial tumors (grades I–IV gliomas), medulloblastomas, and neuroblastomas. NAV3 copy number changes were studied by fluorescence in situ hybridization and correlated to survival analyses. To identify target genes of NAV3 deletion, NAV3 was silenced by siRNA in glioblastoma cell lines and gene expression profiles were analyzed by Agilent 4×44k dual‐color microarrays. Selected upregulations were confirmed by immunohistochemistry and quantitative polymerase chain reaction. We found NAV3 amplifications to dominate in neuronally differentiated tumors, whereas glial tumors showed almost equal proportions of NAV3 deletion and amplification. However, Grade IV gliomas had more frequent NAV3 deletions than grades I–III gliomas. Silencing of NAV3 in glioma cell lines led to the upregulation of receptor genes associated with gonadotropin‐releasing hormone and Jak‐Stat signaling pathways. Kaplan–Meier analysis of the entire clinical tumor material showed association between NAV3 amplifications and favorable prognosis, as well as NAV3 deletions and unfavorable prognosis. With Cox regression model, a hazard ratio of 0.51 was observed for NAV3 amplifications and 1.36 for NAV3 deletions. We conclude that NAV3 may be a potential new prognostic biomarker and a potential therapeutic target. © 2012 Wiley Periodicals, Inc.     

Occupational exposure to gaseous and particulate contaminants originating from additive manufacturing of liquid,powdered, and filament plastic materials and related post-processes

The aim of this study was to measure the concentrations of gaseous and particulate contaminants originated from additive manufacturing operations and post-processes in an occupational setting when plastics were used as feedstock materials. Secondary aims were to evaluate the concentration levels based on proposed exposure limits and target values and to propose means to reduce exposure to contaminants released in additive manufacturing processes. Volatile organic compounds were sampled with Tenax TA adsorption tubes and analyzed with a thermo desorption gas chromatography-mass spectrometry instrument. Carbonyl compounds were sampled with DNPH-Silica cartridges and analyzed with a high-performance liquid chromatography device. Particles were measured with P-Trak instrument and indoor air quality was sampled with IAQ-Calc instrument. Dust mass concentrations were measured simultaneously with a DustTrak DRX instrument and IOM-samplers. Particle concentrations were highest (2070-81 890 #/cm³ mean) during manufacturing with methods where plastics were thermally processed. Total volatile organic compounds concentrations, in contrast, were low (113–317 µg/m³ mean) during manufacturing with such methods, and vat photopolymerization. However, total volatile organic compounds concentrations of material jetting and multi jet fusion methods were higher (1,114–2,496 µg/m³ mean), perhaps because of material and binder spraying, where part of the spray can become aerosolized. Chemical treatment of manufactured objects was found to be a severe volatile organic compounds source as well. Formaldehyde was detected in low concentrations (3–40 µg/m³) in all methods except for material jetting method, in addition to several other carbonyl compounds. Notable dust concentrations (1.4–9.1?mg/m³) were detected only during post-processing of powder bed fusion and multi jet fusion manufactured objects. Indoor air quality parameters were not found to be notably impacted by manufacturing operations. Only low concentrations (below 2?ppm) of CO were detected during several manufacturing processes. All studied additive manufacturing operations emitted potentially harmful contaminants into their environments, which should be considered in occupational additive manufacturing and workplace design. According to the measured contaminant levels it is possible that adverse additive manufacturing related health effects may occur among exposed workers.     

Sleep wake cycling in early preterm infants: Comparison of polysomnographic recordings with a novel EEG-based index

ObjectiveTo document the occurrence of genuine sleep stages in the early preterm babies, and to develop an EEG-based index for following sleep wake cyclicity.MethodsTwelve preterm babies were recruited from a study that assessed ventilator strategies. We used altogether 18 polysomnography recordings that were collected at mean conceptional age of 29.3 (25.9–32.7) weeks. Spontaneous activity transients (SAT) were detected automatically and their cumulative coverage in each 20 s interval was computed from the EEG derivations C3–A2 and O2–A1. Mean SAT% values between sleep stages were compared.ResultsAll babies exhibited all sleep stages, however the sleep was remarkably fragmentary in infants due to their respiratory issues. The EEG index, SAT% showed temporal behavior that strikingly well compared with the sleep stage fluctuations in the hypnogram. In the statistical analysis we found significant differences in all recordings between the deep (quiet) sleep and the REM sleep.ConclusionGenuine sleep states exist in the early preterm babies, and changes in sleep stages are reflected in the EEG activity in a way that can be readily measured by assessing fluctuation of the automatically detected, EEG based index, the SAT%.SignificanceThe findings open a possibility to construct automated analysis or monitoring of sleep wake cyclicity into brain monitors in neonatal intensive care unit.     

No effect of acute l-arginine supplementation on O2 cost or exercise tolerance

The extent to which dietary supplementation with the nitric oxide synthase (NOS) substrate, l-arginine (ARG), impacts on NO production and NO-mediated physiological responses is controversial. This randomised, double blinded, cross-over study investigated the effects of acute ARG supplementation on NO biomarkers, O₂ cost of exercise and exercise tolerance in humans. In one experiment, 15 subjects completed moderate- and severe-intensity running bouts after acute supplementation with 6 g ARG or placebo (PLA). In another experiment, eight subjects completed moderate- and severe-intensity cycling bouts after acute supplementation with 6 g ARG plus 25 g of carbohydrate (ARG + CHO) or an energy-matched dose of carbohydrate alone (CHO). The plasma nitrite concentration was not different after ARG (Pre: 204 ± 79; Post: 241 ± 114 nM; P > 0.05) or ARG + CHO consumption (Pre: 304 ± 57; Post: 335 ± 116 nM; P > 0.05). During moderate-intensity exercise, the steady-state pulmonary $ \dot{V}{\text{O}}_{2} $ was not different, relative to the respective placebo conditions, after ARG (PLA: 2,407 ± 318, ARG: 2,422 ± 333 mL min^?1) or ARG + CHO (CHO: 1,695 ± 304, ARG + CHO: 1,712 ± 312 mL min^?1) ingestion (P > 0.05). The tolerable duration of severe exercise was also not significantly different (P > 0.05) after ingesting ARG (PLA: 551 ± 140, ARG: 552 ± 150 s) or ARG + CHO (CHO: 457 ± 182, ARG + CHO: 441 ± 221 s). In conclusion, acute dietary supplementation with ARG or ARG + CHO did not alter biomarkers of NO synthesis, O₂ cost of exercise or exercise tolerance in healthy subjects.     

ALDH1A1-related stemness in high-grade serous ovarian cancer is a negative prognostic indicator but potentially targetable by EGFR/mTOR-PI3K/aurora kinase inhibitors

Poor chemotherapy response remains a major treatment challenge for high-grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient-derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment-naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment-naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment-naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K-mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K-mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment-naive tumours. EGFR, mTOR-PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.