Subcutaneous adipose tissue classification

The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT) can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT), structural WAT (sWAT) and fibrous WAT (fWAT). dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical). In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for regenerative procedures based on autologous adipose tissues

Biomarkers of potential harm in people switching from smoking tobacco to exclusive e-cigarette use, dual use or abstinence: secondary analysis of Cochrane systematic review of trials of e-cigarettes for smoking cessation

Aims This study aims to compare biomarkers of potential harm between people switching from smoking combustible cigarettes (CC) completely to electronic cigarettes (EC), continuing to smoke CC, using both EC and CC (dual users) and using neither (abstainers), based on behaviour during EC intervention studies. Design Secondary analysis following systematic review, incorporating inverse variance random-effects meta-analysis and effect direction plots. Setting This study was conducted in Greece, Italy, Poland, the United Kingdom and the United States. Participants A total of 1299 adults smoking CC (nine studies) and provided EC. Measurements Measurements were conducted using carbon monoxide (CO) and 26 other biomarkers. Findings In pooled analyses, exhaled CO (eCO) was lower in EC versus EC + CC [mean difference (MD) = −4.40 parts per million (p.p.m.), 95% confidence interval (CI) = −12.04 to 3.24, two studies] and CC (MD = −9.57 p.p.m., 95% CI = −17.30 to −1.83, three studies). eCO was lower in dual users versus CC only (MD = −1.91 p.p.m., 95% CI = −3.38 to −0.45, two studies). Magnitude rather than direction of effect drove substantial statistical heterogeneity. Effect direction plots were used for other biomarkers. Comparing EC with CC, 12 of 13 biomarkers were significantly lower in EC users, with no difference for the 13th. Comparing EC with dual users, 12 of the 25 biomarkers were lower for EC, and five were lower for dual use. For the remaining eight measures, single studies did not detect statistically significant differences, or the multiple studies contributing to the outcome had inconsistent results. Only one study provided data comparing dual use with CC; of the 13 biomarkers measured, 12 were significantly lower in the dual use group, with no statistically significant difference detected for the 13th. Only one study provided data on abstainers. Conclusions Switching from smoking to vaping or dual use appears to reduce levels of biomarkers of potential harm significantly

Different renal phenotypes in related adult males with Fabry disease with the same classic genotype

BACKGROUND: Fabry disease related patients with classical mutation usually exhibit similar severe phenotype especially concerning renal manifestation. METHODS: A dry blood spot screening (DBS) and the DNA analysis has been performed in a 48-year-old man (Patient 1) because of paresthesia. RESULTS: The DBS revealed absent leukocyte \u3b1-Gal A enzyme activity while DNA analysis identified the I354K mutation. Serum creatinine and e-GFR were in normal range and also albuminuria and proteinuria were absent. The brain MRI showed ischemic lesions and a diffuse focus of gliosis in the white matter, while the echocardiogram showed a left ventricular hypertrophy. The renal biopsy performed in the case index showed a massive deposition of zebra bodies. By a familiar investigation, it was recognized that his brother (Patient 2) died 2 years before from sudden death syndrome at the age of 49. He had suffered sporadic and undiagnosed pain at the extremities, a prior cataract, bilateral neurosensorial hearing loss and left ventricular hypertrophy on Echocardiogram. His previous laboratory examinations revealed a normal serum creatinine and the absence of proteinuria. Pedigree analysis of the brothers revealed a high disease burden among family members, with an affected cousin (Patient 3) who progressed early to end-stage renal disease (ESRD) that required renal transplantation. CONCLUSIONS: Here we describe the clinical history of three adult male members of the same family with the same genotype who manifested different presentation and progression of the disease, particularly concerning the renal involvement

Redundancy, Deduction Schemes, and Minimum-Size Bases for Association Rules

Association rules are among the most widely employed data analysis methods in the field of Data Mining. An association rule is a form of partial implication between two sets of binary variables. In the most common approach, association rules are parameterized by a lower bound on their confidence, which is the empirical conditional probability of their consequent given the antecedent, and/or by some other parameter bounds such as "support" or deviation from independence. We study here notions of redundancy among association rules from a fundamental perspective. We see each transaction in a dataset as an interpretation (or model) in the propositional logic sense, and consider existing notions of redundancy, that is, of logical entailment, among association rules, of the form "any dataset in which this first rule holds must obey also that second rule, therefore the second is redundant". We discuss several existing alternative definitions of redundancy between association rules and provide new characterizations and relationships among them. We show that the main alternatives we discuss correspond actually to just two variants, which differ in the treatment of full-confidence implications. For each of these two notions of redundancy, we provide a sound and complete deduction calculus, and we show how to construct complete bases (that is, axiomatizations) of absolutely minimum size in terms of the number of rules. We explore finally an approach to redundancy with respect to several association rules, and fully characterize its simplest case of two partial premises.Comment: LMCS accepted pape

Immune activation, immune senescence and levels of Epstein Barr Virus in kidney transplant patients: Impact of mTOR inhibitors

Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis. 124 kidney transplanted patients were enrolled in this study: 71 were treated with mycophenolic acid (MPA) and 53 treated with mTOR inhibitor (mTORi), both in combination with different doses of calcineurin inhibitor. At the time of the transplant (T0), profile of inflammation/immune activation and immune senescence didn't differ between the two groups, but after one year of treatment (T1) markers were significantly higher in MPA-treated patients; their immunosenescence process was supported by the greater erosion of telomeres despite their younger age. Percentages of activated B cells and levels of EBV-DNA significantly increased in MPA-treated patients, and at T1 were significantly higher in MPA- than in mTORi-treated patients. Overall, these findings indicate that mTOR inhibitors constrain the inflammation/immune activation and senescence status, thus reducing the expansion of EBV-infected B cells and the risk of virus-associated PTLD in kidney transplant recipients. \ua9 2019 The Author

Persistence of antibody responses to the sars-cov-2 in dialysis patients and renal transplant recipients recovered from covid-19

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as “failure”, a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702; transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function

Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.

BACKGROUND: Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection. However, evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid. We aimed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin. METHODS: The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion (Neoral) and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. Analysis was by intention to treat. FINDINGS: 168 patients per group entered phase A. 56 (34%) assigned mycophenolate mofetil and 58 (35%) assigned azathioprine had clinical rejections (risk reduction [RR] on mycophenolate mofetil compared with azathioprine 13.7% [95% CI -25.7% to 40.7%], p=0.44). 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 (16%) taking mycophenolate mofetil and 11 (12%) taking azathioprine had clinical rejections (RR -16.2%, [-157.5% to 47.5%], p=0.71). Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine (phase A 2665 Euros [SD 586] vs Euros 184 [62]; phase B 5095 Euros [2658] vs 322 Euros [170], p<0.0001 for both). INTERPRETATION: In recipients of cadaver kidney-transplants given ciclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive. Standard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil, at least for kidney graft

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

Abstract View references (47) The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P <.001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35). \ua9 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeon