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of clear evidence of benefit. More comprehensive research into the impact of endocannabinoids in the context of endometriosis is required before their use can be recommended or prescribed.

To evaluate whether physical access and the ability to systematically assess the postablation uterine cavity were preserved at 12 months after endometrial ablation with the Cerene cryotherapy device (ChannelMedsystems, Emeryville, CA).

A prospective, multicenter, single-arm study.

In the clinic at 8 US sites and outpatient hospital setting at 2 sites in Canada and 1 site in Mexico.

A total of 230 (of 242) subjects continued in the study at the Month 12 visit after ablation. Two hundred twenty-three subjects were available for a diagnostic hysteroscopic evaluation.

Subjects who had previously been treated with a 2.5-minute cryoablation of the endometrium utilizing the Cerene device underwent a diagnostic hysteroscopy at the Month 12 follow-up visit.

The uterine cavity was accessible in 220 of 223 subjects (98.7%) and not accessible in 3 (1.3%) because of pain (n=2) and cervical stenosis (n=1). Visualization of the uterine cavity was possible in 204 of 220 subjects (92.7%) with one or both tubal ostce hysteroscopy 1 year after the use of the Cerene cryotherapy device is attainable, enabling both diagnostic and therapeutic procedures within the endometrial cavity.

To assess to what degree can digestive symptoms improve after endometriosis surgery for different localizations.

A comparative retrospective study employing data prospectively recorded in the North-West Inter-Regional Female Cohort for Patients with Endometriosis (CIRENDO) from June 2009 to November 2018.

Two referral centers.

A total of 1497 women undergoing surgery because of pelvic endometriosis were divided into 3 groups superficial endometriosis (Group 1, n=396), deep endometriosis sparing the bowel (Group 2, n=337), and deep endometriosis involving the bowel (Group 3, n=764).

Surgery for endometriosis.

Preoperative and postoperative gastrointestinal symptoms were evaluated with standardized questionnaires, including the Gastrointestinal Quality of Life Index (GIQLI) and Knowles-Eccersley-Scott-Symptom questionnaire (KESS). The degree of postoperative improvement in digestive symptoms was compared between the groups. The women in Group 3 were significantly symptomatic in terms of cycle-related gastrointestinal symptoms and scores of standardized questionnaires GIQLI and KESS. According to the 1-year postoperative evaluation, women in Group 3 experienced the most significant improvement in their gastrointestinal symptoms.

Women with severe bowel symptoms and deep endometriosis infiltrating the bowel should be informed about the high probability of symptom improvement after the removal of bowel nodules. Conversely, in women without deep endometriosis, postoperatively, there is less improvement in baseline digestive complaints.

Women with severe bowel symptoms and deep endometriosis infiltrating the bowel should be informed about the high probability of symptom improvement after the removal of bowel nodules. Conversely, in women without deep endometriosis, postoperatively, there is less improvement in baseline digestive complaints.Micropollutants (MP) with varying ozone-reactive moieties were spiked to lake water in the influent of a drinking water pilot plant consisting of an ozonation followed by a biological sand filtration. During ozonation, 227 transformation products (OTPs) from 39 of the spiked 51 MPs were detected after solid phase extraction by liquid chromatography high-resolution mass spectrometry (LC-HRMS/MS). Based on the MS/MS data, tentative molecular structures are proposed. Reaction mechanisms for the formation of a large number of OTPs are suggested by combination of the kinetics of formation and abatement and state-of-the-art knowledge on ozone and hydroxyl radical chemistry. OTPs forming as primary or higher generation products from the oxidation of MPs could be differentiated. However, some expected products from the reactions of ozone with activated aromatic compounds and olefins were not detected with the applied analytical procedure. 187 OTPs were present in the sand filtration in sufficiently high concentrations to elucidate their fate in this treatment step. 35 of these OTPs (19%) were abated in the sand filtration step, most likely due to biodegradation. Only 24 (13%) of the OTPs were abated more efficiently than the parent compounds, with a dependency on the functional group of the parent MPs and OTPs. Overall, this study provides evidence, that the common assumption that OTPs are easily abated in biological post-treatment is not generally valid. Nevertheless, it is unknown how the OTPs, which escaped detection, would have behaved in the biological post-treatment.

Virtual reality (VR) and serious games (SGs) are widespread in rehabilitation for many orthopaedic and neurological diseases. However, few studies have addressed the effects of rehabilitation with VR-based SGs on clinical, gait, and postural outcomes in individuals with total knee replacement (TKR).

The primary objective was the efficacy of balance training using non-immersive VR-based SGs compared to conventional therapy in TKR patients on the Time Up and Go test. Secondary objectives included the efficacy on clinical, gait, and postural outcomes.

We randomly allocated 56 individuals with unilateral TKR to the experimental group (EG) or control group (CG) for 15 sessions (45 min; 5 times per week) of non-immersive VR-based SGs or conventional balance training, respectively. The primary outcome was functional mobility measured by the Timed Up and Go test; secondary outcomes were walking speed, pain intensity, lower-limb muscular strength, independence in activities of daily living as well as gait and pot could be considered an alternative to the conventional approach and can be added to a regular rehabilitation program in TKR patients. The EG had a more physiological duration of the gait stance phase at the end of the treatment than the CG. CLINICALTRIALS.GOV NCT03454256.Technological advances have made it possible to offer home-based chemotherapy to patients without health care professionals being present. Prior studies on effects of home-based treatment lack inclusion of patients with hematologic malignancies. We present data from a multicenter single-arm feasibility and safety study of home-based intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia and their quality of life and psychological wellbeing. This national study included patients from six sites in Denmark who received intensive chemotherapy on programmed CADD Solis infusion pumps through a central venous catheter and were also managed as outpatients during treatment-induced pancytopenia. Data are presented from 104 patients, receiving 272 treatments with 1.096 (mean 4.57, SD 3.0) home infusion days out of 1.644 treatment days (67 %). Sixty-two of 168 (36.9 %) reinduction and consolidation treatment cycles ensuing pancytopenia phases were solely handled in the outpatient clinic. Patients reported high satisfaction with home-based treatment, which had a positive influence on their ability to be involved in their treatment and be socially and physically active. No unexpected events occurred during the intervention. Overall, patients improved in all quality of life outcomes over time. Home-based intensive chemotherapy treatment was feasible and safe in this population. ClinicalTrials.gov identifier NCT04904211.A phase II study was conducted to ascertain whether sequential exposure to decitabine followed by rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor would result in better responses than decitabine alone. Newly diagnosed acute myelogenous leukemia (AML) patients who were >65 years old and not eligible for intensive induction regimens or patients with relapsed or refractory AML received 10 days of decitabine followed by 12 days of rapamycin in cycle 1 and 5 days of decitabine followed by 17 days of rapamycin in subsequent cycles. The composite complete remission rate (CR) was 33 % (CR plus CR with incomplete count recovery). Median overall survival was 7.7 months in newly diagnosed elderly AML patients and 6.6 months in relapsed/refractory AML patients. Twenty-four evaluable patients were enrolled, and the study did not meet its primary endpoint of demonstrating a significant improvement in composite CR rate with the combination as compared to an established historical CR rate of 25 % with decitabine alone. Despite that, the survival rates in relapsed/refractory cases appear comparable to what is reported with other salvage regimens, and no significant patterns of non-hematologic toxicity were noted. 50 % of subjects in the de novo group achieved a composite CR which is significantly higher (p = 0.02) than the rate of 25 % with decitabine alone. This trial is registered at clinical trials.gov as NCT02109744.

Prothrombin complex concentrates (PCCs) are plasma products containing a mixture of four inactive/proactive coagulation factors. Axitinib The activated forms of human coagulation factors, like Thrombin (FIIa), Convertin (FVIIa), activated Christmas factor (FIXa) and the activated Stuart-Prower factor (FXa), are impurities in PCCs. Until now no valid assay exists to differentiate the non activated proform (inactive) from active coagulation factor isoforms in PCCs in one measurement. Therefore, the aim of this study was to establish a mass spectrometry (LC-MS/MS)-based assay to address this issue in the ready to use medicinal product.

Bottom-up proteomics combining double digestion (Glu-C & Lys-C) and LC-MS/MS, was used to differentiate the inactive and active forms of the coagulation factors Prothrombin (FII), Proconvertin (FVII), Christmas factor (FIX) and the Stuart-Prower-factor (FX) in PCCs.

A targeted pseudo-multiple reaction monitoring (pMRM-LC-MS/MS)-assay was developed for the specific detection of foliquid chromatography tandem mass spectrometry (LC-MS/MS) run.Rutin is a flavonoid compound with many pharmacological activities, including antioxidation, anti-inflammation and cardiovascular and cerebrovascular protection. However, there are great limitations in clinical application in view of its poor solubility and slow absorption in vivo. In this study, a pharmacokinetic and pharmacodynomic model was adopted to study the correlation of the pharmacokinetics and pharmacodynomics of rutin in lipopolysaccharide-induced acute lung injury mice. Rutin was intragastrically administered continuously for 5 days at a dose of 200 mg/kg/d, and pharmacokinetic and pharmacodynamic indicators were measured every day after administration, including the blood concentration of rutin, the W/D ratio of lungs, the nitric oxide content and the expression levels of TLR4, TRAF6, IκB and P-IκB proteins. The results indicated that rutin can exert an anti-inflammatory protective effect by improving lung tissue injury, significantly decreasing the synthesis of the inflammatory mediator nitric oxide, and inhibiting the protein expression levels of TLR4, TRAF6 and P-IκB. The absorption of rutin conformed to a one-compartment model with the pharmacokinetic parameters as follows t1/2α= 9.76 h, t1/2β= 19.44 h, Tmax= 24.00 h, Cmax= 22.65 μg/ml and AUC(0-t)= 518.58 μg/ml·h. A PK-PD combination model was established to fit the optimal administration time of rutin with a one-compartment-Sigmod Emax model connected to the effect site. Meanwhile,the PK-PD combination model was a better approach for evaluating the relationships between the five pharmacodynamic indicators and the pharmacokinetic characteristics of rutin. The correlation between the pharmacokinetics and pharmacodynamics of rutin was quantitatively analysed to provide a theoretical basis for the research and development of new anti-inflammatory drugs in clinical practice.

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