Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis.

Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated in the PIONEER clinical trial program, and a recently published network meta-analysis allowed comparison with further injectable GLP-1 receptor agonists. The present study aimed to assess the short-term cost- effectiveness of oral semaglutide 14 mg versus subcutaneous once-weekly dulaglutide 1.5 mg, once-weekly exenatide 2 mg, twice-daily exenatide 10 µg, once-daily liraglutide 1.8 mg, once-daily lixisenatide 20 µg, and once-weekly semaglutide 1 mg, in terms of the cost per patient achieving glycated hemoglobin (HbA1c) targets (cost of control).Materials and methods: Cost of control was calculated by dividing the annual treatment costs associated with an intervention by the proportion of patients achieving the treatment target with an intervention, with outcomes calculated for targets of HbA1c ≤6.5% and HbA1c <7.0% for all included GLP-1 receptor agonists. Annual treatment costs were accounted in 2019 United States dollars (USD), based on 2019 wholesale acquisition cost.Results: For the treatment target of HbA1c ≤6.5%, once-weekly semaglutide 1 mg and oral semaglutide 14 mg were associated with the lowest costs of control, at USD 15,430 and USD 17,383 per patient achieving target, respectively. Similarly, the cost of control was lowest with once-weekly semaglutide 1 mg at USD 12,627 per patient achieving target, followed by oral semaglutide 14 mg at USD 13,493 per patient achieving target for the target of HbA1c <7.0%. All other interventions were associated with higher cost of control values for both targets.Conclusions: Oral semaglutide 14 mg is likely to be cost-effective versus dulaglutide, exenatide (once weekly and twice daily), liraglutide, and lixisenatide in terms of bringing people with type 2 diabetes to glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0% in the US.

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial.

OBJECTIVE: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and relationship with preterm delivery, low birthweight and perinatal infections.

OBJECTIVE: To determine the prevalence of bacterial vaginosis (BV) in the second trimester of pregnancy in a Danish population using the Schmidt criteria and to examine whether BV was associated with subsequent preterm delivery, low birthweight or perinatal infections. DESIGN: Prospective cohort study. SETTING: Department of Obstetrics and Gynaecology at a University Hospital, Denmark. POPULATION: Three thousand five hundred and forty pregnant women aged 18 years or more. METHODS: A smear from the vagina was obtained from all women, air-dried and stored for subsequent diagnosis of BV. After rehydration with isotonic saline, the smear was examined in a phase-contrast microscope at 400x, and the numbers of lactobacilli morphotypes and small bacterial morphotypes were counted. A score for BV was calculated according to the method described by Schmidt. The outcome of pregnancy from 20 weeks of gestation was examined in the 3262 singleton pregnant women who were included in this study before 20 weeks of gestation. The relationship between BV and adverse outcome of pregnancy was examined by univariate and multivariate analyses. MAIN OUTCOME MEASURES: Prevalence of BV, preterm delivery (<37 weeks), low birthweight (<2500 g), preterm delivery of a low-birthweight infant and clinical chorioamnionitis. RESULTS: The prevalence of BV was 16%, and the rate of preterm delivery was 5.2% in the study population of 3262 singleton pregnant women who were included before 20 weeks of gestation. Mean birthweight was significantly lower in infants of women with BV than in infants of women without BV (3408 versus 3511 g, P < 0.01). Univariate analyses showed that BV was marginally associated with preterm delivery but significantly associated with low birthweight, preterm delivery of a low birthweight infant, indicated preterm delivery and clinical chorioamnionitis. Multivariate analyses, which adjusted for previous miscarriage, previous preterm delivery, previous conisation, smoking, gestational diabetes, fetal death and preterm premature rupture of membranes, showed that BV was significantly associated with low birthweight (OR 1.95, 95% CI 1.3-2.9), preterm delivery of a low-birthweight infant (OR 2.5, 95% CI 1.6-3.9), indicated preterm delivery (OR 2.4, 95% CI 1.4-4.1) and clinical chorioamnionitis (OR 2.7, 95% CI 1.4-5.1). CONCLUSIONS: The prevalence of BV determined using the Schmidt criteria in the early second trimester of pregnancy was similar to that found in similar studies. The presence of BV before 20 weeks of gestation was an independent risk factor for delivery of an infant with low birthweight, preterm delivery of a low-birthweight infant, indicated preterm delivery and clinical chorioamnionitis.

Perinatal complications in women with gestational diabetes mellitus.

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.

Determination of zuclopenthixol and its main N-dealkylated metabolite in biological fluids using high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection.

A highly sensitive high-performance liquid chromatographic (HPLC) method for the assay of cis-(Z)-clopenthixol (zuclopenthixol) in urine and plasma has been developed. Following solid-phase extraction, the samples are chromatographed using reversed-phase ion-pairing HPLC. After separation, the solutes, having a thioxanthene structure, are transformed on-line into thioxanthones in a photochemical reactor. The thioxanthones are highly fluorescent compounds, and therefore, low detection limits are obtained when using fluorescence detection. Detection limits for zuclopenthixol and its N-dealkylated metabolite, in plasma as well as in urine, using fluorescence detection with excitation at 260 nm and emission at 435 nm, were found to be 0.05 ng/ml and 0.2 ng/ml, respectively. The chromatographic system separates the cis-(Z)- and trans-(E)-isomers of clopenthixol from its main dealkylated metabolite. Furthermore, the chromatographic system is very suitable for study of the photochemical reaction, since the chloro-thioxanthone and thioxanthone are well separated from the isomers of clopenthixol.

Correlation between distal nephron enzyme activity, structure and function in rats during lithium and lithium plus neuroleptic treatment.

The histochemical activities of nonspecific acid and alkaline phosphatases, NADH- and NADPH-tetrazolium reductases, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated in kidneys from rats treated with lithium and lithium plus neuroleptics. During the first 8 weeks of lithium treatment the activity of NADH-tetrazolium reductase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activity in the collecting ducts increased. The other enzymes did not change. After 8 weeks of treatment no further changes in enzyme activity occurred. Withdrawal of lithium caused normalization of enzyme activity after 8 weeks. A decrease in concentration ability was found in parallel with the increase in enzyme activities (p less than 0.001). The changes in enzyme activity were not significantly correlated to morphological changes in the collecting ducts. Treatment with neuroleptics alone caused no change in enzyme activity. During combined lithium plus neuroleptic treatment the enzyme activities changed in a similar way as during lithium therapy, but the changes were less pronounced. In parallel, a less pronounced decrease in concentration ability was found during this treatment.

Functional and structural changes in the rat kidney by long-term lithium treatment.

The relation between functional and structural renal changes induced by lithium was studied in rats during long-term treatment and after withdrawal of lithium. Administration of LiCl in the diet for up to 21 weeks caused marked polyuria associated with a significant lowering of renal concentrating ability assessed by dehydration and vasopressin tests. Plasma creatinine and plasma urea were not significantly changed by the treatment. Upon withdrawal of lithium water intake and concentrating ability were normalized within 4--8 weeks. Lithium caused focal light microscopic changes in the distal convoluted tubule and the collecting duct, consisting of nuclear and cellular polymorphism and, after prolonged treatment, dilatation of tubular lumens with tubular cell atrophy. These changes appeared later than the concentrating defect and persisted when lithium was withdrawn after prolonged treatment. No significant correlation was found between the degree of tubular changes and water intake or concentrating ability. It is concluded that the reversible diabetes insipidus induced by lithium in rats cannot be explained directly by the light microscopical changes observed in the distal part of the nephron, although the structural changes may be secondary to the polyuric state induced by lithium.

Comparative study of hysterosalpingography and laparoscopy in infertile patients.

The diagnostic accuracy of hysterosalpingography (HSG) and laparoscopy was investigated in 168 consecutive patients with infertility of at least 2 years' duration. There was agreement between the results of both methods in 57.7 per cent of the patients. Among 54 patients having normal HSG, 16 (29.6 per cent) exhibited abnormalities at laparoscopy. Among 114 patients with abnormal HSG, 28 (24.6 per cent) had entirely normal internal genitalia at laparoscopy. The greatest discrepancy between the HSG and laparoscopic diagnoses was found in peritubal adhesions. Intrauterine abnormalities were diagnosed by HSG in only 2.4 per cent of the patients. Complications of laparoscopy were few and none was serious. For a conclusive evaluation of the tubal factor in infertility, one must consider abandoning HSG entirely in favor of laparoscopy.

Very-low-calorie diet in the treatment of massive obesity: preliminary experience.

Twenty-two consecutive obese patients were given very-low-calorie diet (VLCD) in the form of a casein and lactose preparation dissolved in orange juice containing 43.0 g protein, 30.4 g carbohydrate and 1.1 g lipid in a total of 317 kcal (1.3 MJ) daily. VLCD was given intermittently in eight-week periods alternating with three-week periods of conventional diet (900-1200 kcal, 3.8-5.0 MJ) to ensure recuperation of lean body mass and to establish a therapy which may facilitate indefinite patient compliance. In case of persisting hunger, diethyl-propion was given in small doses. The median observation time was nine weeks (range 1-37 weeks). The median weight loss was 15.5 kg (range 3.8-39.2 kg), and the median overweight decreased from 85.5 per cent (range 43-135 per cent) to 61.0 per cent (range 19-100 per cent). Blood glucose and cholesterol fell significantly (P < 0.01), and no major side-effects were observed.