Effects of physical exercise on adiponectin, leptin, and inflammatory markers in childhood obesity: systematic review and meta-analysis

Background: New findings on adipose tissue physiology and obesity-Associated inflammation status suggest that modification of the adipokine level can be relevant for the long-Term prevention of obesity-Associated chronic disease. Objectives: The scope of the present study was to investigate the effectiveness of physical exercise in reducing the systemic inflammation related to obesity in children. Methods: We conducted a systematic review with meta-Analysis of controlled randomized trials, identified through electronic database search, which investigated the effect of physical exercise, without concomitant dietary intervention, on adiponectin, leptin, and/or other inflammatory markers in children up to age 18 years with a body mass index greater than the 95th percentile for age and sex. Results: Seven trials were included in the meta-Analysis, with a total of 250 participants. Compared with the control group without any lifestyle modification, the physical exercise resulted in a reduction in leptin [standardized mean difference (SMD)-1.13; 95% confidence interval (95%CI):-1.89 to-0.37; I2 = 79.9%] and interleukin-6 (SMD-0.84; 95%CI:-1.45 to-0.23, I2 = 0.9%) and an increase in adiponectin plasma concentration (SMD 0.69; 95%CI: 0.02-1.35; I2 = 74.3%). Conclusions: These results indicate that physical exercise improved the inflammatory state in children with obesity. It is unclear whether this effect can reduce the risk of cardiovascular and metabolic disease in adulthood. Clinical trials with a uniform intervention protocol and outcome measurements are required to put our knowledge on adipose tissue biology into a clinical perspective

Time dependent Markovian master equation beyond the adiabatic limit

We develop a Markovian master equation that models the evolution of systems subject to arbitrary driving and control fields. Our approach combines time rescaling and weak-coupling limits for the system-environment interaction with a secular approximation. The derivation makes use of the adiabatic time evolution operator in a manner that allows for the efficient description of strong driving, while recovering the adiabatic master equation in the appropriate limit. To illustrate the effectiveness of our approach, we apply it to the paradigmatic case of a two-level (qubit) system subjected to a form of periodic driving that remains unsolvable using a Floquet representation. We demonstrate the reliability and broad scope of our approach by benchmarking the solutions of the derived reduced time evolution against numerically exact simulations using tensor networks. Our results provide rigorous conditions that must be satisfied by phenomenological master equations for driven systems that do not rely on first principles derivations.Comment: 20+8 pages, 5 figures. Comments are welcom

Recurrent extreme bilateral gigantomastia caused by pseudoangiomatous stromal hyperplasia (PASH) syndrome: a case report

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare and benign medical condition in which the breast tissue is affected by an abnormal myofibroblastic proliferation, which mimics a low-grade sarcoma angiomatous proliferation. PASH usually presents itself either as a palpable mass or as an incidental diagnosis during breast specimens' histological examination. A few cases have been reported in the literature of a diffuse form of breast PASH syndrome in which the clinical presentation is a bilateral form of gigantomastia without palpable masses. In such cases, the optimal surgical management is still debated due to a significant risk of relapse after breast reduction. Mastectomy seems to be the endpoint of this condition in relapsing cases. Recent studies report a good outcome with a Tamoxifen regimen when surgery cannot be performed, supporting a hormonal component for the etiology of the condition. This study reports on an extremely rare case of bilateral, rapid, and severe PASH in a young patient, presenting as a truly disabling gigantomastia that forced the patient to use a wheelchair due to the excessive breast weights (25 kg the right breast and 21 kg the left). We describe her complicated medical history, her diagnosis, and our course of treatment

Compact and tunable stretch bioreactor advancing tissue engineering implementation. Application to engineered cardiac constructs

Physical stimuli are crucial for the structural and functional maturation of tissues both in vivo and in vitro . In tissue engineering applications, bioreactors have become fundamental and effective tools for provid- ing biomimetic culture conditions that recapitulate the native physical stimuli. In addition, bioreactors play a key role in assuring strict control, automation, and standardization in the production process of cell-based products for future clinical application. In this study, a compact, easy-to-use, tunable stretch bioreactor is proposed. Based on customizable and low-cost technological solutions, the bioreactor was designed for providing tunable mechanical stretch for biomimetic dynamic culture of different engineered tissues. In-house validation tests demonstrated the accuracy and repeatability of the imposed mechanical stimulation. Proof of concepts biological tests performed on engineered cardiac constructs, based on de- cellularized human skin scaffolds seeded with human cardiac progenitor cells, confirmed the bioreactor Good Laboratory Practice compliance and ease of use, and the effectiveness of the delivered cyclic stretch stimulation on the cardiac construct maturation

A low-cost 3D-printed sample-holder for stirring-based decellularization of biological tissues

An innovative, low-cost, 3D-printed sample-holder is proposed for reproducible and effective stirring-based decellularization of biological tissues. The sample-holder was designed to be low-cost, easy to use with conventional laboratory equipment, and manufacturable through 3D printing. During stirring-based decellularization, the sample holder exposes the samples to convective flow, enhancing the reagent transport while protecting the samples from disruptive forces. Computational fluid dynamics analyses were carried out to elucidate the developing hydrodynamics. Explanatory tests, performed on human cardiac tissue samples, demonstrated the effectiveness of the presented device

A low-cost scalable 3D-printed sample-holder for agitation-based decellularization of biological tissues

Decellularized extracellular matrix is one of the most promising biological scaffold supporting in vitro tissue growth and in vivo tissue regeneration in both preclinical research and clinical practice. In case of thick tissues or even organs, conventional static decellularization methods based on chemical or enzymatic treatments are not effective in removing the native cellular material without affecting the extracellular matrix. To overcome this limitation, dynamic decellularization methods, mostly based on perfusion and agitation, have been proposed. In this study, we developed a low-cost scalable 3D-printed sample-holder for agitation-based decellularization purposes, designed for treating multiple specimens simultaneously and for improving efficiency, homogeneity and reproducibility of the decellularization treatment with respect to conventional agitation-based approaches. In detail, the proposed sample-holder is able to house up to four specimens and, immersed in the decellularizing solution within a beaker placed on a magnetic stirrer, to expose them to convective flow, enhancing the solution transport through the specimens while protecting them. Computational fluid dynamics analyses were performed to investigate the fluid phenomena establishing within the beaker and to support the sample-holder design. Exploratory biological tests performed on human skin specimens demonstrated that the sample-holder reduces process duration and increases treatment homogeneity and reproducibility

Donor Cell Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: A Case Report and Literature Review

The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT. In the subsequent ten years, the AML relapsed three times and the patient underwent chemotherapy and three further HSCTs; donors were the same sister from the first HSCT, an unrelated donor, and his mother. The patient died during the third relapse. The DCL was characterized since onset by an acquired translocation between chromosomes 9 and 11, with a molecular rearrangement between the MLL and MLLT3 genes-a quite frequent cause of AML. In all of the relapses, the malignant clone had XX sex chromosomes and this rearrangement, thus indicating that it was always the original clone derived from the transplanted sister's cells. It exhibited the ability to remain quiescent in the BM during repeated chemotherapy courses, remission periods and HSCT. The leukemic clone then acquired different additional anomalies during the ten years of follow-up, with cytogenetic results characterized both by anomalies frequent in AML and by different, non-recurrent changes. This type of cytogenetic course is uncommon in AML

A randomized phase II trial of Captem or Folfiri as second-line therapy in neuroendocrine carcinomas

Background: Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. Methods: This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. Results: The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4-60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7-46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9-51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. Conclusion: The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. Gov identifier: NCT03387592