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Aims: To assess the effect of sodium-glucose cotransporter-2 inhibitor dapagliflozin on natriuresis, blood pressure (BP) and volume status in patients with chronic kidney disease (CKD) without diabetes. Materials and methods: We performed a mechanistic open-label study (DAPASALT) to evaluate the effects of dapagliflozin on 24-hour sodium excretion, 24-hour BP, extracellular volume, and markers of volume status during a standardized sodium diet (150 mmol/d) in six patients with CKD. In parallel, in a placebo-controlled double-blind crossover trial (DIAMOND), we determined the effects of 6 weeks of dapagliflozin on markers of volume status in 53 patients with CKD. Results: In DAPASALT (mean age 65 years, mean estimated glomerular filtration rate [eGFR] 39.4 mL/min/1.73 m2, median urine albumin:creatinine ratio [UACR] 111 mg/g), dapagliflozin did not change 24-hour sodium and volume excretion during 2 weeks of treatment. Dapagliflozin was associated with a modest increase in 24-hour glucose excretion on Day 4, which persisted at Day 14 and reversed to baseline after discontinuation. Mean 24-hour systolic BP decreased by −9.3 (95% confidence interval [CI] −19.1, 0.4) mmHg after 4 days and was sustained at Day 14 and at wash-out. Renin, angiotensin II, urinary aldosterone and copeptin levels increased from baseline. In DIAMOND (mean age 51 years, mean eGFR 59.0 mL/min/1.73 m2, median UACR 608 mg/g), compared to placebo, dapagliflozin increased plasma renin (38.5 [95% CI 7.4, 78.8]%), aldosterone (19.1 [95% CI −5.9, 50.8]%), and copeptin levels (7.3 [95% CI 0.1, 14.5] pmol/L). Conclusions: During a standardized sodium diet, dapagliflozin decreased BP but did not increase 24-hour sodium and volume excretion. The lack of increased natriuresis and diuresis may be attributed to activation of intra-renal compensatory mechanisms to prevent excessive water loss.

The Chicxulub impact event at ca. 66 Ma left in its wake the only complex crater on Earth with a preserved peak ring, characterized by a well-developed magnetic anomaly low. To date, little is known about its magnetic properties. The joint Integrated Ocean Drilling Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drill core M0077A revealed that the peak ring consists of uplifted and strongly deformed granitoid basement rocks overlain by a 130-m-thick impact melt and suevite layer. Pre- and postimpact hydrothermal systems affected this basement with maximum temperatures up to 450 °C. We used microscopy, mineral chemistry, temperature-dependent magnetic susceptibility, and hysteresis properties to characterize the magnetic mineralogy of pre-, syn-, and postimpact rocks. Compared to its amount of pure, stoichiometric shocked magnetite, the granitoid basement shows low magnetic susceptibility, which is in line with earlier experimental studies indicating that shock reduces magnetic susceptibility. Cation-substituted magnetite with varying compositions in the melt rocks carries a higher induced and remanent magnetization compared to the basement. In the granitoid basement, magnetite was partially oxidized to hematite by a pre-impact hydrothermal event, but at lithological contacts with high-temperature impact melt rock, this hematite was locally retransformed back to magnetite. Elsewhere in the granitoid basement, the temperature reached in the hydrothermal system was too low for hematite retransformation. It was also too low to anneal all the lattice defects in the shocked magnetite, which likely occurs above 540 °C. The presence of shocked magnetite in the granitoid basement well explains the magnetic anomaly low due to its unusually low induced magnetization.

BACKGROUND: This metaregression analysis examined which behavioral techniques that are commonly used in behavioral parent and teacher training programs for children with attention-deficit/hyperactivity disorder (ADHD) were related to program effectiveness on children's behavioral outcomes. METHODS: We included 32 randomized controlled trials (N = 2594 children) investigating behavioral parent training, teacher training, or a combination, in children with ADHD under 18 years. Outcomes were symptom counts of total ADHD, inattention, and hyperactivity-impulsivity and behavioral problems. The dosage of techniques was extracted from the intervention manuals. Metaregression was used to assess which techniques and intervention characteristics (setting, delivery method, duration, and home-school collaboration) were associated with intervention effectiveness. RESULTS: Higher dosage of psycho-education for parents was associated with smaller effects on behavioral problems and, only in case of parent training, also with smaller effects on ADHD symptoms. Higher dosage of teaching parents/teachers to use negative consequences was associated with larger effects on behavioral problems. Individual training compared with group training was associated with larger effects on ADHD and hyperactivity-impulsivity symptoms. CONCLUSIONS: This study provides first insights into the specific techniques that are essential in behavioral parent and teacher training programs for children with ADHD. This knowledge can eventually be used to improve and tailor interventions. ispartof: CHILD AND ADOLESCENT MENTAL HEALTH vol:28 issue:2 pages:258-268 ispartof: location:England status: published

A paleomagnetic study performed in Plio-Pleistocene volcanic rocks of two localities in the Southern Central Andes is presented. The region corresponds to the transition zone between the Central and the Patagonian Andes. In the latter, deformation is almost exclusively controlled by the dextral-strike slip Liquiñe-Ofqui Fault Zone, that extends from ∼47 °S to ∼38 °S and accommodates the deformation generated by the oblique subduction of the Nazca Plate below South America. To the north of ∼36 °S, deformation is mainly contractional. Our study was carried out in the transition zone between both tectonic regimes. Sampling consisted of 31 paleomagnetic sites distributed in two localities: the Loncopué (∼38.0 °S, 70.7 °W) and Andacollo (∼37.2 °S, 70.8 °W) areas. We sampled Pliocene and Pleistocene volcanic rocks with ages younger than 5 Ma. After stepwise demagnetization and principal component analysis, site mean remanence directions were computed. Both localities show non-significant clockwise rotations of 1.7° ± 14.4° (Loncopué) and 8.1° ± 8.4° (Andacollo). Although the presently available database does not support significant tectonic rotation of the Andacollo lavas, preliminary results obtained from upper Miocene volcanics in a nearby area indicating ∼20° of clockwise rotation, encourage further studies to improve the resolution of the paleomagnetic data to determine if crustal block rotations have been, or still are, part of the Andean deformational processes. A revision of previously published paleomagnetic data in the northern Patagonian Andes suggests that, against original claims, no significant tectonic rotations associated to the Liquiñe-Ofqui Fault Zone, between ∼39 and 37.5 °S, can be unambiguously demonstrated.

Contains fulltext : 240648.pdf (Publisher’s version ) (Open Access) Impulsive and risky decision-making peaks in adolescence, and is consistently associated with the neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD), regardless of age. In this brief review, we demonstrate the similarity of theoretical models explaining impulsive and risky decision-making that originate in two relatively distinct literatures (i.e. on adolescence and on ADHD). We summarize research thus far and conclude that the presence of ADHD during adolescence further exacerbates the tendency that is already present in adolescents to make impulsive and risky decisions. We also conclude that much is still unknown about the developmental trajectories of individuals with ADHD with regard to impulsive and risky decision-making, and we therefore provide several hypotheses that warrant further longitudinal research. 7 p.

OBJECTIVE: Behavioral parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but it is unknown which of its components are most effective. This meta-regression analysis investigated which specific behavioral techniques that parents learn in parent training are associated with effects on parental outcomes. METHOD: A search was performed for randomized controlled trials on parent training for children with ADHD, with positive parenting, negative parenting, parenting sense of competence, parent-child relationship quality, and parental mental health as outcome measures. After screening 23,026 publications, 29 studies contributing 138 effect sizes were included (N = 2,345). For each study, the dosage of 39 behavioral techniques was derived from intervention manuals, and meta-regression determined which techniques were related to outcomes. RESULTS: Parent training had robust small- to medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. A higher dosage of techniques focusing on the manipulation of antecedents of behavior was associated with better outcomes on parenting sense of competence and parental mental health, and a higher dosage of techniques focusing on reinforcement of desired behaviors was related to larger decreases in negative parenting. Higher dosages of psychoeducation were negatively related to parental outcomes. CONCLUSION: Although techniques were not investigated in isolation, the results suggested that manipulation of antecedents of behavior and reinforcement techniques are key components of parent training for children with ADHD in relation to parental outcomes. These exploratory findings may help to strengthen and tailor parent training interventions for children with ADHD. ispartof: Journal Of The American Academy Of Child And Adolescent Psychiatry vol:61 issue:4 pages:478-494 ispartof: location:United States status: Published online

International audience; The Paleocene lavas from Dianzhong Formation (E1d) in Linzhou basin of southern Lhasa terrane are a key target for paleomagnetic investigations into the timing and paleolatitude of the initial India-Asia collision. Controversy exists, however, on whether these rocks preserve a primary remanent magnetization. Here we reanalyze previously published thermal demagnetization data and report detailed rock magnetic results and petrographic observations of these rocks. We find that the original magnetic carrier, a magmatic multidomain Ti-poor titanomagnetite, underwent significant grain size reduction and was variably reacted to single-domain maghemite and nano-hematite. Such strong alteration may have resulted from successive hydrothermal events: a first event related to the ∼52 Ma dike intrusions into the E1d that accompanied a massive ignimbrite eruption deposited above the E1d producing heating up to 300 °C; and a secondary event related to the 42 - 27 Ma southward overthrusting of the basin, heating the E1d up to 130 – 145 °C. Unblocking/inversion temperature spectra of the authigenic maghemite and nano-hematite overlap with those of the titanomagnetite, implying that the primary remanence of the E1d lavas has been contaminated or replaced by thermoviscous and chemical remanent magnetizations. Thus the isolated characteristic remanent magnetization from these rocks, whether slightly or completely altered, cannot be considered primary and should not be used for paleolatitudinal determination. Our study confirms that hydrothermal alteration can seriously jeopardize the remanence carried by titanomagnetite and thus should be tested for paleomagnetic investigations of rock units from tectonically active areas.

Behavioral parent and teacher training and stimulant medication are recommended interventions for children with attention-deficit/hyperactivity disorder (ADHD). However, not all children with ADHD receive this evidence-based care, and the aim of the current study was to find out why. More specifically, we investigated clinicians’ policy, guideline use, and attitudes towards medication and parent training when treating children with ADHD, as well as several factors that could affect this. A total of 219 Dutch clinicians (mainly psychologists, psychiatrists and educationalists) completed a survey. Clinicians were likely to recommend medication more often than parent training, and clinicians’ policy to recommend medication and parent training was positively associated with their attitudes towards these interventions. Less experienced clinicians and those with a non-medical background reported lower rates of guideline use, whereas clinicians with a medical background reported less positive attitudes towards parent training. Furthermore, a substantial portion of the clinicians based their decision to recommend parent training on their clinical judgement (e.g., prior estimations of efficacy, perceived low abilities/motivation of parents), and many clinicians reported barriers for referral to parent training, such as waiting lists or a lack of skilled staff. To achieve better implementation of evidence-based care for children with ADHD, guidelines should be communicated better towards clinicians. Researchers and policy-makers should further focus on barriers that prevent implementation of parent training, which are suggested by the discrepancy between clinicians’ overall positive attitude towards parent training and the relatively low extent to which clinicians actually advise parent training.

BACKGROUND AND AIMS: Amanita phalloides poisoning causes severe liver damage which may be potentially fatal. Several treatments are available, but their effectiveness has not been systematically evaluated. We performed a systematic review to investigate the effect of the most commonly used therapies: N-acetylcysteine (NAC), benzylpenicillin (PEN), and silibinin (SIL) on patient outcomes. In addition, other factors contributing to patient outcomes are identified. METHODS: We searched MEDLINE and Embase for case series and case reports that described patient outcomes after poisoning with amanitin-containing Amanita mushrooms. We extracted clinical characteristics, treatment details, and outcomes. We used the liver item from the Poisoning Severity Score (PSS) to categorize intoxication severity. RESULTS: We included 131 publications describing a total of 877 unique cases. The overall survival rate of all patients was 84%. Patients receiving only supportive care had a survival rate of 59%. The use of SIL or PEN was associated with a 90% (OR 6.40 [3.14-13.04]) and 89% (OR 5.24 [2.87-9.56]) survival rate, respectively. NAC/SIL combination therapy was associated with 85% survival rate (OR 3.85 [2.04, 7.25]). NAC/PEN/SIL treatment group had a survival rate of 76% (OR 2.11 [1.25, 3.57]). Due to the limited number of cases, the use of NAC alone could not be evaluated. Additional analyses in 'proven cases' (amanitin detected), 'probable cases' (mushroom identified by mycologist), and 'possible cases' (neither amanitin detected nor mushroom identified) showed comparable results, but the results did not reach statistical significance. Transplantation-free survivors had significantly lower peak values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), and international normalized ratio (INR) compared to liver transplantation survivors and patients with fatal outcomes. Higher peak PSS was associated with increased mortality. CONCLUSION: Based on data available, no statistical differences could be observed for the effects of NAC, PEN or SIL in proven poisonings with amanitin-containing mushrooms. However, monotherapy with SIL or PEN and combination therapy with NAC/SIL appear to be associated with higher survival rates compared to supportive care alone. AST, ALT, TSB, and INR values are possible predictors of potentially fatal outcomes.

The drift history of the Lhasa terrane from Gondwana to Asia plays a crucial role in understanding the Tethys evolution and true polar wander (TPW). However, few reliable paleomagnetic results from Jurassic strata are currently available for reconstructing its northward journey. We performed a combined paleomagnetic and geochronological study on Bima Formation strata in the Xigaze area. Combined with previous results from the Sangri area, our results reveal a paleolatitude of 8 ± 4°S at ∼180 Ma for the reference point (29.3°N, 90.3°E). Along with other paleomagnetic results from the Triassic to Cretaceous, our new results suggest that the Lhasa terrane motion accelerated from ∼2 cm/yr during ∼220–180 Ma to ∼17 cm/yr during ∼180–170 Ma. Paleolatitude information of the North Qiangtang terrane and Tethyan Himalaya is calculated from paleopoles that meet five criteria, which include (a) structural control, (b) well-determined rock age, (c) stepwise demagnetizations, (d) a minimum of 25 specimens or 8 sites are contained, and (e) robust field or reversal tests are provided. Both terranes also show significant acceleration during their northward motion, which may be related to oceanic slab subduction. Thus, all Gondwana-derived microcontinents seem to share a significant acceleration during their northward motion. In addition, recent paleomagnetic results from volcanic rocks dated at ∼155 Ma subdivide the overall northward motion during ∼170–130 Ma into two stages, which include a southward drift during ∼170–155 Ma followed by northward motion during ∼155–130 Ma. These results support the fast Late Jurassic TPW during a ∼10 Myr time span.

Behavioral parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but knowledge on the differential effects of behavioral techniques for specific subgroups of children is very limited. Attachment representations of children with ADHD may affect how receptive children are to changes in parenting. In this study, we investigated whether specific behavioral techniques were more or less effective for children with ADHD in relation to their attachment representations. We included parents of 74 children with ADHD (4–11 years, M = 8.15) who took part in a larger randomized controlled microtrial in which they were randomized to a two session training in antecedent-based techniques (i.e., stimulus control techniques: rules, instructions; n = 26), a two session training in consequent-based techniques (i.e., contingency management techniques: praise, rewards, ignoring; n = 25) or a waitlist control condition (n = 23). We examined whether attachment representation moderated the effectiveness of a) training versus waitlist, and b) antecedent- versus consequent-based techniques. Attachment representations were measured with a story stem task, the intervention outcome was daily parent-rated problem behaviors of the children. Attachment representation did not moderate the effects of the training compared to the waitlist. However, compared to antecedent-based techniques, consequent-based techniques were less effective for more securely and less disorganized attached children, and particularly effective for more disorganized attached children. This was the first study examining attachment as a moderator of behavioral techniques for ADHD. If replicated, the findings of this study can be used for treatment development and tailoring.

In some lockdowns during the COVID-19 pandemic in 2020 and 2021, schools were closed and children attended distance learning.To investigate parental experiences of the effects of distance learning on the wellbeing of child and parent(s), and whether this differed between children with and without mental health problems and their parents.Parents of children with (n = 192) and without (n = 271) mental health problems reported their experiences with distance learning. We investigated whether experiences differed between groups of parents, and whether experiences were influenced by characteristics of parents.Parents of children with mental health problems reported the quality of distance learning and the ability of their child to participate as lower relative to other parents. These differences increased when parents themselves were in higher need of support. General experiences and the levels of stress reported by parents did not differ between groups. Parents reported an increase in their childrsquo;s digital media use, particularly for children with mental health problems.Children with mental health problems seem more negatively affected by distance learning, especially when parents have problems themselves. These findings are in line with multiple recent studies and argue for minimizing distance learning.

PurposeValue-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients.MethodsWe retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs.Results271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke’s cleft cyst (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250).ConclusionsLength of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.

Ophiolites, fragments of oceanic lithosphere exposed on land, are typically found as isolated klippen in intensely deformed fold-thrust belts spanning hundreds to thousands of kilometers along-strike. Ophiolites whose geochemistry indicates that they formed above subduction zones, may have been relics of larger, once-coherent, oceanic lithosphere tracts that formed the leading edge of an upper plate below which subduction occurred; such tracts were subsequently dismembered by deformation and erosion during orogenesis and uplift. However, to what extent the first-order original coherence is maintained between ophiolitic klippen is difficult to assess. Here, we aim to evaluate whether the Jurassic forearc ophiolites overlying subduction complex rocks in California, now scattered over 1000 km and dismembered by the wider San Andreas Fault Zone, still maintain their original lithospheric coherence. To this end we (i) compile available crustal ages from all ophiolite klippen exposed in the Jurassic ophiolite belt of the western United States; (ii) review and kinematically reconstruct post-middle Jurassic deformation that occurred between the modern western coast and the stable North American craton to restore the original positions of the ophiolite fragments relative to each other and to North America, and (iii) perform a paleomagnetic analysis of a sheeted dyke sections of the Mt. Diablo and Josephine ophiolites to estimate the orientation of the spreading axis at which the Jurassic Californian forearc ophiolites formed. The latter analysis reveals that the original ridge orientation likely trended ∼080–260°, near-perpendicular to the orientation of the trench along the western margin of the ophiolite belt. We show that with these constraints, a straightforward ridge-transform system can explain the age distributions of the ophiolites with spreading rates of 6–7 cm/a. Our analysis shows that the Jurassic ophiolites of California may be considered klippen of a single sheet of oceanic lithosphere that accreted at a supra-subduction zone spreading ridge. In addition, we show that kinematic and paleomagnetic analysis of ophiolite belts may provide novel constraints on the kinematic evolution of accretionary orogens and the plates now lost to subduction.

INTRODUCTION: Nicotine is an addictive and poisonous agent. The recent development of e-cigarettes has caused a new demand for highly concentrated nicotine-containing solutions. These concentrated nicotine solutions have also increased the risk of nicotine overdoses.AREAS COVERED: Essential factors for nicotine exposure are the concentration of the nicotine-containing e-liquid solution and its pharmacokinetics. Liquid nicotine refills contain nicotine in varying concentrations, which vary widely between and within products. The pharmacokinetics of nicotine are dependent on the route of administration, renal/hepatic clearance and urinary pH. The dose is another essential determinant of nicotine exposure. There is a considerable discrepancy between the generally accepted lethal dose and symptoms reported in case studies. Ingested doses correlate poorly to clinical symptoms. Symptoms of liquid nicotine toxicity vary from mild to severe between patients and are the result of overstimulation of nicotinic acetylcholine receptors, which may lead to fatal respiratory failure and cardiovascular collapse.EXPERT OPINION: The literature on nicotine-containing e-liquid intoxications originating from vaping device refills are mainly case reports. Based on these case reports, we propose a treatment plan which is primarily symptomatic. Research should focus on providing insight on its toxicity, based on oral and transdermal pharmacokinetics and on toxicodynamics.

International audience; Editors of JGR-Solid Earth express their appreciation to those who served as peer reviewers for the journal in 2021.

Background: SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes. Methods: DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18–75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin–angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694. Findings: Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730–1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI −16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by −6·6 mL/min per 1·73 m2 (–9·0 to −4·2; p

This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.53–0.81]. These effects were consistent across baseline estimated glomerular filtration rate (eGFR) and haemoglobin A1c subgroups. In this review we combine the results of the CREDENCE trial with those of several cardiovascular outcome trials with SGLT2 inhibitors and show that, unexpectedly, patients with lower eGFR levels may have greater benefit with respect to cardiovascular outcome than patients with normal kidney function. The cardio- and renoprotective effects of SGLT2 inhibitors seem to be independent of their glucose-lowering effects, as shown in several post hoc analyses. In this review we discuss the alleged mechanisms of action that explain the beneficial effects of this novel class of drugs. Moreover, we discuss whether these findings indicate that this class of drugs may also be beneficial in non-diabetic chronic kidney diseases.

Airway inflammation and remodeling are characteristic features of asthma, with both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2-chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin α4 and α5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling, and inflammation in asthma. Expression of both laminin α4 and α5 was observed in the human and mouse ASM bundle. In vitro, laminin α4 was found to promote a pro-proliferative, pro-contractile, and pro-fibrotic ASM cell phenotype. In line with this, treatment with laminin α4 and α5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin α4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM α4-chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin α4 in the ASM bundle. This study, for the first time, indicates a prominent role for laminin α4 in ASM function and in inflammation, AHR, and remodeling in asthma, whereas the role of laminin α5 is more subtle.

Objective: To evaluate the results of active non-surgical treatment in patients diagnosed with adult periodontitis treated in a specialized clinic for periodontology. Material & Methods: In total, 1182 patients with adult periodontitis received active non-surgical therapy, which involved professional oral hygiene instruction, scaling and root planing, supragingival polishing and elective systemic antimicrobial medication. The results of this therapy were based on a full-mouth periodontal chart as assessed at the time of evaluation. Successful treatment as periodontal pocket depth (PPD) ≤5 mm was the main outcome parameter with bleeding on pocket probing as secondary outcome. Patient-related factors such as smoking and severity of periodontitis at baseline and site-related factors such as tooth type, furcation involvement and endodontic treatment were analysed. Possible relations with assessed parameters and the success of active periodontal therapy were evaluated. Results: Overall 39% of the patients reached the successful treatment objective and a mean bleeding on pocket probing tendency of 14%. Treatment success appeared to be dependent on tooth type where the results at single-rooted front teeth (85%) and premolar teeth (78%) were more successful than at molar teeth (47%). Analysis revealed that in 55% of the cases furcation involvement at molars was associated with the absence of success. Endodontic treatment was associated with absence of success in 8%-11% of the cases. Smoking negatively influences successful treatment outcome (P < 0.001). Conclusion: Active non-surgical periodontal therapy in patients with adult periodontitis resulted in approximately one third of the cases in the success endpoint of PPD ≤ 5mm. Sub-analysis showed that the outcome appeared to be dependent on tooth type, furcation involvement, severity of periodontal disease at intake and smoking status.

Highlights • Basement membrane composition is changed in the airways of patients with obstructive airway diseases. • Basement membrane changes are linked to disease characteristics in patients. • Mechanisms behind the altered BM composition remain to be elucidated. • Laminin and collagen IV affect key pathological processes in obstructive airway diseases., Increased and changed deposition of extracellular matrix proteins is a key feature of airway wall remodeling in obstructive pulmonary diseases, including asthma and chronic obstructive pulmonary disease. Studies have highlighted that the deposition of various basement membrane proteins in the lung tissue is altered and that these changes reflect tissue compartment specificity. Inflammatory responses in both diseases may result in the deregulation of production and degradation of these proteins. In addition to their role in tissue development and integrity, emerging evidence indicates that basement membrane proteins also actively modulate cellular processes in obstructive airway diseases, contributing to disease development, progression and maintenance. In this review, we summarize the changes in basement membrane composition in airway remodeling in obstructive airway diseases and explore their potential application as innovative targets for treatment development.

Across the Miocene–Pliocene boundary (MPB; 5.3 million years ago, Ma), late Miocene cooling gave way to the early-to-middle Pliocene Warm Period. This transition, across which atmospheric CO2 concentrations increased to levels similar to present, holds potential for deciphering regional climate responses in Asia—currently home to more than half of the world’s population— to global climate change. Here we find that CO2-induced MPB warming both increased summer monsoon moisture transport over East Asia, and enhanced aridification over large parts of Central Asia by increasing evaporation, based on integration of our ~1–2-thousand-year (kyr) resolution summer monsoon records from the Chinese Loess Plateau aeolian red clay with existing terrestrial records, land-sea correlations, and climate model simulations. Our results offer palaeoclimate-based support for ‘wet-gets-wetter and dry-gets-drier’ projections of future regional hydroclimate responses to sustained anthropogenic forcing. Moreover, our high-resolution monsoon records reveal a dynamic response to eccentricity modulation of solar insolation, with predominant 405-kyr and ~100-kyr periodicities between 8.1 and 3.4 Ma., Global warming drove ‘wet gets wetter and dry gets drier’ climate shifts in Asia ~5.3 million years ago with monsoon pacing by ~400,000 and ~ 100,000 year cycles. This could be a template for future Asian climate response to anthropogenic warming.

To accomplish a successful cardiac surgery, cardiopulmonary bypass (CPB) is often utilized to give the surgeon a bloodless field while keeping the patient hemodynamically stable. The perfusionist is responsible for running the heart-lung machine and other devices such as: cell savers, anticoagulation and blood gas management or mechanical circulatory support. Critical times during CPB include going on, cross clamp on and off, cardioplegia delivery, and termination. Troubleshooting is a component that is often overlooked but can be detrimental to delivering the best patient care. To help eliminate these errors, checklists and protocols are put into place to make sure standardized measures are taken pre/intra/post CPB. Safety techniques like deep hypothermic circulatory arrest is performed for certain cardiac surgeries to prevent end organ damage. Perfusion technology is constantly evolving; however, this chapter looks to help build a solid foundation for understanding CPB and supporting devices.

Attention-Deficit/Hyperactivity Disorder (ADHD) in children is associated with several adverse family characteristics, such as higher parenting stress, more conflicted parent-child relationships, lower parental competence, and higher levels of parental psychopathology. Hence, children with ADHD more often grow up under suboptimal circumstances, which may impact the development of their attachment representations. Here, we investigated whether children with ADHD have more insecure and disorganized attachment representations than their typically developing peers, and which factors could explain this association. We included 104 children between 4 and 11 years old, 74 with ADHD (without Conduct Disorder) and 30 typically developing control children. Children completed a state-of-the-art story stem task to assess their attachment representation, and we measured parents' expressed emotion (as an index of parent-child relationship quality), parents' perceived sense of competence, parental education levels, and parent-rated ODD symptoms of the child. We found that, after controlling for multiple comparisons, children with ADHD had less secure and more ambivalent and disorganized attachment representations relative to their typically developing peers. These group differences were independent of comorbid ODD and parental education levels. There were no group differences on avoidant attachment representations. Explorative analyses within the ADHD group showed that attachment representations were not related to parent-child relationship quality, perceived parenting competence, parental education levels, and comorbid ODD symptoms. We conclude that children with ADHD disproportionately often have attachment problems. Although this conclusion is important, treatment implications of this co-occurrence are yet unclear as research on ADHD and attachment is still in its infancy. ispartof: Brain Sciences vol:11 issue:11 pages:1-13 ispartof: location:Switzerland status: published

BackgroundA diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management.MethodsPatients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression.ResultsIn 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 – 63.8), TSH ConclusionThe Dx scan can potentially change clinical management before treatment with I-131, but the yield is low. A Dx-scan should only be considered for patients with a high pre-scan risk of a change in management, based on patient history and prior center-based surgical outcomes.