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55, 1.28) (P-interaction = 0.60). These results suggest that the CV effects of semaglutide may extend to patients with type 2 diabetes across the CV risk continuum.

To evaluate the use of hybrid closed-loop glucose control with faster-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D).

In a double-blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed-loop system incorporating the Cambridge model predictive control algorithm was used.

In an intention-to-treat analysis, the proportion of time sensor glucose was in the target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard insulin aspart; mean-adjusted difference -0.6% [95% CI -1.8% to 0.7%]; p < .001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%-3.2%] vs. 2.9% [1.7%-4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%-0.7%] vs. 0.7% [0.2%-0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. read more 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred.

The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.

The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

To examine the association of low back pain (LBP) and lumbar kyphosis with functional disabilities and knee symptoms in patients with knee osteoarthritis (OA).

We analyzed 586 participants (80.1% female; age, 68.8 ± 5.2 years) from the Nagahama Study who were aged ≥60 years and had radiographically confirmed knee OA. The Knee Scoring System (KSS) was used to assess functional disabilities and knee symptoms. LBP was defined as the presence of any persistent back pain for more than 3 months. Lumbar kyphosis was determined by skin-surface methods using a computer-aided electronic device called the Spinal Mouse. Multiple linear regression analysis was used for assessing the association of LBP and lumbar kyphosis with the KSS scores. Subgroup analyses based on sex were also performed.

LBP and lumbar kyphosis were independently associated with a lower KSS function score after adjustment for covariates (mean difference [95%CI, confidence interval] = -4.96 [-7.56 to -2.36] points for LBP alone, -4.47 [-8.51 to -0.43] points for lumbar kyphosis alone, and -13.86 [-18.86 to -8.86] points for the coexistence of LBP and lumbar kyphosis, respectively). The coexistence of LBP and lumbar kyphosis in women was associated with a lower KSS symptom score (mean difference [95%CI] = -4.49 [-6.42 to -2.55] points).

These findings suggest that both LBP and lumbar kyphosis are useful clinical signals indicating functional disability and knee symptoms in patients with knee OA.

These findings suggest that both LBP and lumbar kyphosis are useful clinical signals indicating functional disability and knee symptoms in patients with knee OA.The development of integrated systems that mimic the multi-stage stiffness change of marine animals such as the sea cucumber requires the design of molecularly tailored structures. Herein, we used an integrated biomimicry design to fabricate a sea cucumber mimic using sidechain polypseudorotaxanes with tunable nano-to-macroscale properties. A series of polyethylene glycol (PEG)-based sidechain copolymers were synthesized to form sidechain polypseudorotaxanes with α-cyclodextrins (α-CDs). By tailoring the copolymers' molecular weights and their PEG grafting densities, we rationally tuned the sizes of the formed polypseudorotaxanes crystalline domain and the physical crosslinking density of the hydrogels, which facilitated 3D printing and the mechanical adaptability to these hydrogels. After 3D printing and photo-crosslinking, the obtained hydrogels exhibited large tensile strain and broad elastic-to-plastic variations upon α-CD (de)threading. These discoveries enabled a successful fabrication of a sea cucumber mimic, demonstrating multi-stage stiffness changes.

To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy.

An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks.

After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic

Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.Body size has fundamental impacts on animal ecology and physiology but has been strongly influenced by recent climate change and human activities, such as size-selective harvesting. Understanding the ecological and life history consequences of body size has proved difficult due to the inseparability of direct effects of body size from processes connected to it (such as growth rate and individual condition). Here, we used the cnidarian Hydra oligactis to directly manipulate body size and understand its causal effects on reproduction and senescence. We found that experimentally reducing size delayed sexual development and lowered fecundity, while post-reproductive survival increased, implying that smaller individuals can physiologically detect their reduced size and adjust life history decisions to achieve higher survival. Our experiment suggests that ecological or human-induced changes in body size will have immediate effects on life history and population dynamics through a growth-independent link between body size, reproduction and senescence.

To evaluate outcomes and prognostic factors after decompressive hemilaminectomy in paraplegic medium to large breed dogs with extensive epidural hemorrhage (DEEH) and thoracolumbar intervertebral disc extrusion (TL-IVDE).

Retrospective, cohort, descriptive study.

Fifty-nine client-owned dogs.

Medical records and advanced imaging were reviewed for paraplegic dogs with DEEH. Ambulatory status 6 months after surgery and postoperative complications were recorded. Multiple logistic regression models were constructed to explore prognostic factors.

Records of 22 dogs with and 37 dogs without pelvic limb pain perception at presentation were included. Median age of dogs was 5 years (interquartile range, 4-7), and mean weight was 26.9 kg (SD, ±9.71). Labradors and Labrador mixes were most common (17/59 [28.8%]). Recovery of ambulation occurred in 17 of 22 (77.3%) dogs with and in 14 of 37 (37.8%) dogs without pain perception prior to surgery. Progressive myelomalacia was recorded in three of 59 (5.1%) dogs, one with pain perception and two without pain perception at presentation. Postoperative complications (14/59 [23.7%]) were common. Factors independently associated with outcome included clinical severity (odds ratio [OR] 0.179, P = .005), number of vertebrae with signal interruption in half Fourier single-shot turbo spin-echo sequences (HASTEi; OR, 0.738; P = .035), and ratio of vertebral sites decompressed to HASTEi (OR, 53.79; P = .03).

Paraplegic medium to large breed dogs with DEEH have a less favorable outcome after surgical decompression than paraplegic dogs with TL-IVDE.

Dogs with DEEH can have severe postoperative complications. Loss of pain perception and increased HASTEi are associated with a poor outcome, while more extensive decompression improves outcome.

Dogs with DEEH can have severe postoperative complications. Loss of pain perception and increased HASTEi are associated with a poor outcome, while more extensive decompression improves outcome.

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