Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Long-Term Improvements in Pulmonary Function 5 Years After Bariatric Surgery

Background

Obesity is associated with reduced pulmonary function. We evaluated pulmonary function and status of asthma and obstructive sleep apnoea syndrome (OSAS) before and 5 years after bariatric surgery.

Methods

Spirometry was performed at baseline and 5 years postoperatively. Information of asthma and OSAS were recorded. Of 113 patients included, 101 had undergone gastric bypass, 10 duodenal switch and 2 sleeve gastrectomy.

Results

Eighty (71 %) patients were women, mean preoperative age was 40 years and preoperative weight was 133 kg in women and 158 kg in men. Five years postoperatively, weight reduction was 31 % (42 kg; p?<?0.001) in women and 24 % (38 kg; p?<?0.001) in men. Forced expiratory volume in 1 s (FEV1) increased 4.1 % (116 ml; p?<?0.001) in women and 6.7 % (238 ml; p?=?0.003) in men. Forced vital capacity (FVC) increased 5.8 % (209 ml; p?<?0.001) in women and 7.6 % (349 ml; p?<?0.001) in men. Gender and weight loss were independently associated with the improvements in FEV1 and FVC. At follow-up, FEV1 had increased 36 % of the difference towards the estimated normal FEV1, and there was a corresponding 70 % recovery of FVC. These improvements occurred despite an expected decline in pulmonary function by age during the study period. Of the asthmatics and OSAS patients, 48 and 80 %, respectively, were without symptoms 5 years postoperatively.

Conclusions

Pulmonary function measured with spirometry was significantly improved 5 years after bariatric surgery, despite an expected age-related decline during this period. Symptoms of asthma and OSAS also improved.     

Rheumatic mitral valve stenosis mimicking advanced lung cancer

This report describes a patient with a perihilar mass and mediastinal lymphadenopathy mimicking advanced lung cancer. The patient, a 45-year old regular smoker, was admitted to hospital for dyspnea and tachyarrhythmia, and during hospitalization he was diagnosed with severe rheumatic mitral valve stenosis (MVS) and aortic regurgitation as well as pulmonary venous hypertension. Surgical valve replacement and removal of an atrial thrombus was delayed considerably by diagnostic work-up for suspected malignancy. After cardiac surgery had been performed, recovery was uneventful. On follow-up 1 year later, echocardiography showed well-functioning prosthetic mitral and aortic valves, and normal findings on chest X-ray. Perihilar masses and mediastinal lymphadenopathy presented in this case constitute infrequent yet established findings in MVS, resulting from pulmonary venous congestion and hypertension, and focal lymphedema.     

Water column monitoring of the biological effects of produced water from the Ekofisk offshore oil installation from 2006 to 2009

The Norwegian water column monitoring program investigates the biological effects of offshore oil and gas activities in Norwegian waters. In three separate surveys in 2006, 2008, and 2009, bioaccumulation and biomarker responses were measured in mussels (Mytilus edulis) and Atlantic cod (Gadus morhua) held in cages at known distances from the produced water (PW) discharge at the Ekofisk oil field. Identical monitoring studies performed in all three years have allowed the biological effects and bioaccumulation data to be compared, and in addition, enabled the potential environmental benefits of a PW treatment system (CTour), implemented in 2008, to be evaluated. The results of the 2009 survey showed that caged animals were exposed to low levels of PW components, with highest tissue concentrations in mussels located closest to the PW discharge. Mussels located approximately 1-2 km away demonstrated only background concentrations of target compounds. Concentrations of polycyclic aromatic hydrocarbons (PAH) and alkyl phenol (AP) metabolites in the bile of caged cod were elevated at stations 200-250 m from the discharge. There was also a signal of exposure relative to discharge for the biomarkers CYP1A in fish and micronuclei in mussels. All other fish and mussel biomarkers showed no significant exposure effects in 2009. The mussel bioaccumulation data in 2009 indicated a lower exposure to the PW effluent than seen previously in 2008 and 2006, resulting in an associated general improvement in the health of the caged mussels. This was due to the reduction in overall discharge of PW components (measured as oil in water) into the area in 2009 compared to previous years as a result of the improved PW treatment system.     

Standardized submaximal exercise testing in never smokers: a normative study.

In a population survey on the south-western coast of Norway, 373 never smokers aged 18-73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1.0 l min(-1), 80% of the subjects reached 1.5 l min(-1) and 50% of the subjects reached 2.0 l min(-1). The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1.5 and 2.0 l min(-1) were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1.0 l min(-1) in women and 1.5 l min(-1) in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0.05), ventilation (P<0.001) and heart rate (P<0.001), while in men age was a significant predictor only of ventilation (P<0.001) during the bicycle exercise protocol.     

Different pH requirements for entry of the two picornaviruses,human rhinovirus 2 and murine encephalomyocarditis virus

The entry into cells of human rhinovirus 2 (HRV 2) and murine encephalomyocarditis (EMC) virus was studied by the use of light-sensitive virus grown in the presence of acridine orange (HRV 2) and neutral red (EMC). HeLa cells were protected against infection with HRV 2 by NH₄Cl, monensin, and other compounds known to increase the pH of intracellular vesicles. Preincubation of the cells with the same compounds reduced the ability of the cells to bind [³⁵S]methionine-labeled HRV 2, apparently due to inhibition of recycling of endocytosed receptors back to the cell surface. The cells were also protected against infection when HRV 2 was bound to cells on ice and the cells were then incubated at 37° with the different compounds. This indicates that low pH is also necessary for some event in the entry process taking place after the virus is bound to the cells. In contrast, compounds which increase the pH in acidic intracellular compartments did not protect mouse L-cells against infection with EMC-virus, and the entry of the virus was inhibited by low pH in the medium. This inhibition was partly overcome by the presence of the ionophore monensin, which elevates the pH in endosomes and lysosomes. Possibly, EMC virus enters the cytosol from vesicles with neutral or slightly alkaline pH.     

Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) variability in asymptomatic never-smoking men

We examined the effects from subjects, technicians and spirometers on within-session variability in successful recordings of forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) in 4989 asymptomatic never-smoking men. All eligible men aged 30–46 years living in western Norway (n = 45 380) were invited to a cross-sectional community survey. Information on respiratory symptoms, smoking habits and occupational exposures was obtained from a self-administered questionnaire. Three successful FEV₁ and FVC recordings were obtained in 26 368 attendants using three dry-wedge bellow spirometers operated by 10 different technicians. Within-subject standard deviation (SD) from three recordings of FEV₁ and FVC was on average 102 and 106 ml, respectively, and increased with height (14 and 17 ml, respectively, per 10 cm) and body mass index (BMI) (11 and 14 ml, respectively, per 5 kg m^?2). Between-subject SD of the mean of three FEV₁ and FVC recordings was 591 and 754 ml, respectively, and increased in groups of increasing height (43 and 40 ml, respectively, per 10 cm). Small, but significant, differences were observed between technicians in within-subject SD and in levels of FEV₁ and FVC. Homogeneity of between-subject variability, necessary for linear regression analysis, was obtained using FEV₁ and FVC divided by height squared. In conclusion, within-subject variability in three successful spirometric recordings was small, but dependent on height and BMI of the subjects as well as technician performance. The observed heterogeneity in between-subject variation in FEV₁ and FVC levels disappeared when each variable was divided by height squared. Novel multiple linear regression equations for FEV₁/height² and FVC/height² were developed to be used in evaluating the effects from occupational airborne exposures in Nordic men aged 30–46 years.     

Standardized submaximal exercise testing in never smokers: a normative study

In a population survey on the south‐western coast of Norway, 373 never smokers aged 18–73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1·0 l min^–1, 80% of the subjects reached 1·5 l min^–1 and 50% of the subjects reached 2·0 l min^–1. The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1·5 and 2·0 l min^–1 were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1·0 l min^–1 in women and 1·5 l min^–1 in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0·05), ventilation (P<0·001) and heart rate (P<0·001), while in men age was a significant predictor only of ventilation (P<0·001) during the bicycle exercise protocol.