Doughertymunro1460
g challenges in diabetes modeling.PRIME T2D Model projects outcomes consistent with those from clinical trials.The model is designed to be a useful tool for informing healthcare policy in T2D.
The PRIME T2D Model is a product-independent analysis tool that is available online and offers new approaches to long-standing challenges in diabetes modeling and may become a useful tool for informing healthcare policy.HIGHLIGHTSThe PRIME Type 2 Diabetes (T2D) Model is a new, product-independent simulation model.The model offers new approaches to long-standing challenges in diabetes modeling.PRIME T2D Model projects outcomes consistent with those from clinical trials.The model is designed to be a useful tool for informing healthcare policy in T2D.We retrospectively analyzed perirenal and subcutaneous fat thickness and their dynamics from baseline to end-of-treatment computerized-tomography scans in a cohort of 118 newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with unfavorable features treated with R-DA-EPOCH regimen. Higher revised-international-prognostic-index (R-IPI) score was significantly associated with higher baseline perirenal and lower subcutaneous fat thickness. Up to 51% patients experienced perirenal and 40% subcutaneous fat-tissue loss during immunochemotherapy period. R-DA-EPOCH feasibility, toxicity and obtained response to therapy did not significantly differ regarding baseline perirenal and subcutaneous fat measurements whereas higher number of febrile-neutropenia cycles was associated with more pronounced subcutaneous fat loss. In multivariate-analyses subcutaneous fat loss of ≥6% (hazard-ratio (HR) =4.58, p less then 0.001) and achieving response to therapy (HR = 0.03, p less then 0.001) predicted overall-survival, and baseline subcutaneous fat thickness ≤24 mm (HR = 3.14, p = 0.023), baseline minimal perirenal fat thickness ≤8 mm (HR = 2.44, p = 0.042) and achieving response to therapy (HR = 0.04, p less then 0.001) predicted progression-free-survival independently of each other.Chimeric antigen receptor T (CAR-T) cells are a promising approach in hematopoietic malignancies. We evaluated the safety and efficacy of a combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma (R/RMM). Twenty-two R/RMM patients, with a median age of 56 years and a median number of previous therapies of 8, were included in the study. Both CAR-T cells infusion doses were 2.0 × 106/kg. The overall response rate (ORR) was 90.9%, with 12 patients (54.5%) achieving a strict complete response/complete response (sCR/CR). The 24-month overall survival (OS) rate was 56.6%, and the progression-free survival (PFS) rate was 48.7%. Cytokine release syndrome (CRS) of grades 1-2 occurred in 16 patients (72.7%) and of grade ≥3 in six patients (27.3%). Immune effector cell-associated neurotoxic syndrome (ICANS) of grades 1-2 occurred in three patients (13.6%). The combination therapy is potential in R/RMM patients.Trial registration The patients were enrolled in clinical trials registered as ChiCTR1800017051.
To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M).
Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL).
Age at examination ranged from 7months to 18years (median 2.3years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological (
<.01). There was an increased risk for heart defects in children with psychomotor delay (
=.04). Pathogenic genetic abnormalities were identified in 10/24cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100).
Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.
Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.In this study, amphiphilic block copolymer mPEG-cholic acid was synthesized in conjunction with TPGS as stabilizer to prepare multifunctional micelles. The formed polymeric micelles (PCTm) were used for the delivery of paclitaxel (PTX) and bufalin (BF). PEG group could enhance solubility and extend circulation time, while cholic acid groups achieved the liver targeted function. Combinations of these approaches could realize a synergistic therapeutic effect in the treatment of advanced hepatocellular carcinoma. CLSM in vitro results demonstrated that drug capsulation into PCTm could enhance cellular uptake. FCM results confirmed the uptake amount of C6/PCTm was 7.5-fold higher than that of free C6 after incubation for 2 h. Competitive inhibition test proved the Na+-taurocholate co-transporting polypeptide (NTCP) involved in the uptake mechanism of PCTm. Meanwhile, in vivo imaging assays demonstrated that the fluorescence intensity of Cy5.5/PCTm was higher than that of free Cy5.5 on liver and tumor with extended circulation time to 48 h. In addition, in vivo studies confirmed that the combined therapy exhibited the strongest tumor inhibition rate of 82.29% with lower systemic toxicity. Hence, these results indicated that PCTm could provide a promising strategy for targeting hepatocellular carcinoma and achieve the goal of synergism and attenuation.
To investigate the association between arterial stiffness and functional capacity in individuals with chronic stroke and compare the arterial stiffness between individuals with better and poor functional capacity.
Cross-sectional study.
Individuals after chronic stroke have their arterial stiffness index evaluated by augmentation index heart rate adjusted for 75bpm (AIx@75), assessed by Mobil-O-Graph® device (IEM, Stolberg, Germany), in percent, on the paretic upper limb. Functional capacity was assessed with the Duke Activity Status Index (DASI) in metabolic equivalent (METS). The individuals were assigned into two groups better (DASI ≥ 31.95) and poor (DASI < 31.95) functional capacity. Pearson's correlation and t test were used for analysis.
Twenty-eight individuals (arterial stiffness 23.8±10% and functional capacity 29±19 METS) were included. The association between arterial stiffness and functional capacity was negative and statistically significant, with moderate magnitude (r=-0.53, p <.001). Individuals who had better functional capacity have lower arterial stiffness indices (AIx@75=17.4% versus 27.4% in better and lower functional capacity, respectively) (p=.01).
Arterial stiffness of the paretic upper limb has a negative association with functional capacity.
Arterial stiffness of the paretic upper limb has a negative association with functional capacity.Increased oxidative stress in diabetic wound areas impairs wound healing. Wnt agonist 1 Quercetin exhibits significant antioxidant properties. We investigated the effects of topical quercetin on antioxidant status in diabetic wound areas and its effect on wound healing in rats. A 2 cm2 cutaneous wound was produced on the back of streptozotocin induced diabetic and normal rats. Rats were divided into three groups of 20 normal healthy control group, diabetic group and quercetin treated diabetic group. The control and diabetic groups were treated topically with ointment base once daily for 21 days. The quercetin treated diabetic rats were treated similarly with ointment containing quercetin. The quercetin treated diabetic group exhibited increased levels of catalase, glutathione peroxidase, superoxide dismutase and total thiols compared to the diabetic group. Nitrite levels in the diabetic group were decreased significantly on day 3 compared to the healthy control group. Malondialdehyde levels were decreased in the quercetin treated diabetic group compared to the diabetic group. The expression of proliferating cell nuclear antigen) (PCNA) was greater in the quercetin treated diabetic group on day 7 compared to healthy control and diabetic groups. Formation of granulation tissue and the quality of healed tissue was improved in the quercetin treated diabetic group compared to the diabetic group. Quercetin improves antioxidant status in wounds of diabetic rats and stimulates the proliferation phase, which accelerates wound healing.
Assessing the functional level of children with severe cerebral palsy (CP) requires sensitive tools. In this study, an 'assessment tool' was developed based on the Test of Infant Motor Performance (TIMP) for this population and the reliability and validity evaluated.
Five physical therapists administered the 'assessment tool' to six children (3-6years old with a diagnosis of CP, GMFCS Level V). Subtest I of the Gross Motor Function Measure (GMFM-88) was also administered. Intra- and inter-rater reliability were assessed, and the concurrent validity between the 'assessment tool' and GMFM-88 calculated.
The intra-rater reliability, a comparison of the total scores on the 'assessment tool' (live test) and the videotaped rescoring of the same test one month later showed consistency among four of the five therapists (ICC=
0.7545 to 0.979). The inter-rater reliability varied on some of the items but the total score on the 'assessment tool' showed good reliability (ICC
0.816). Scores of children with dyskinesia were less stable. The Spearman's rank correlation coefficient was not significant. Therapists provided recommendations for item revisions.
Further development of an 'assessment tool' appears justified; a larger study using a version with revised administration guidelines and items should be undertaken to re-verify the psychometrics properties of the 'assessment tool.'
Further development of an 'assessment tool' appears justified; a larger study using a version with revised administration guidelines and items should be undertaken to re-verify the psychometrics properties of the 'assessment tool.'
Exploratory laparotomy is considered the gold standard treatment for women with suspected uterine rupture. We aimed to investigate the feasibility and safety of laparoscopy as an alternative for laparotomy for the management of hemodynamically stable women with suspected postpartum uterine rupture.
We conducted a case series study including all women who were diagnosed with postpartum uterine rupture following vaginal delivery in a university-affiliated tertiary hospital, between November 2012 and July 2021. Until 2016, all women with suspected post-partum uterine rupture underwent laparotomy. Following 2016, a new tailored protocol based on laparoscopy for the management of postpartum uterine rupture in hemodynamically stable women was implemented. A comparison was made between women who underwent emergent laparoscopy to laparotomy.
During the study period 17 women were diagnosed with postpartum uterine rupture. From January 2012 to January 2016, four cases of uterine rupture were diagnosed, all of whom underwent laparotomy.
