Diagnostic study on an immunochromatographic rapid test for schistosomiasis: comparison between use on serum and on blood spot from fingerprick

An immunochromatographic rapid test (ICT; Schistosoma ICT IgG-IgM, LDBIO Diagnostics) demonstrated high sensitivity (96%) in the diagnosis ofSchistosoma mansoniandS. haematobium. To date, the test has been validated for use on serum only, but in the absence of lab equipment, blood drop from fingerprick could be a useful option. This method is acquiring more interest because of the high flow of migrants rapidly moving across Italy and other European countries

Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues

MicroRNAs (miRNAs) belong to a family of small non‐coding RNAs (sncRNAs) playing important roles in human carcinogenesis. Multiple investigations reported miRNAs aberrantly expressed in several cancers, including high‐grade serous ovarian carcinoma (HGS‐OvCa). Quantitative PCR is widely used in studies investigating miRNA expression and the identification of reliable endogenous controls is crucial for proper data normalization. In this study, we aimed to experimentally identify the most stable reference sncRNAs for normalization of miRNA qPCR expression data in HGS‐OvCa. Eleven putative reference sncRNAs for normalization (U6, SNORD48, miR‐92a‐3p, let‐7a‐5p, SNORD61, SNORD72, SNORD68, miR‐103a‐3p, miR‐423‐3p, miR‐191‐5p, miR‐16‐5p) were analysed on a total of 75 HGS‐OvCa and 30 normal tissues, using a highly specific qPCR. Both the normal tissues considered to initiate HGS‐OvCa malignant transformation, namely ovary and fallopian tube epithelia, were included in our study. Stability of candidate endogenous controls was evaluated using an equivalence test and validated by geNorm and NormFinder algorithms. Combining results from the three different statistical approaches, SNORD48 emerged as stably and equivalently expressed between malignant and normal tissues. Among malignant samples, considering groups based on residual tumour, miR‐191‐5p was identified as the most equivalent sncRNA. On the basis of our results, we support the use of SNORD48 as best reference sncRNA for relative quantification in miRNA expression studies between HGS‐OvCa and normal controls, including the first time both the normal tissues supposed to be HGS‐OvCa progenitors. In addition, we recommend miR‐191‐5p as best reference sncRNA in miRNA expression studies with prognostic intent on HGS‐OvCa tissues

Renal function and physical fitness after 12-mo supervised training in kidney transplant recipients

To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations

Renal Function in Kidney and Liver Transplant Recipients After A 130-km Road Cycling Race

Background: A few patients, after receiving solid organ transplantation, return to performing various sports and competitions; however, at present, data no study had evaluated the effects of endurance cycling races on their renal function. Methods: Race times and short form (36) health survey questionnaires of 10 kidney transplant recipients (KTR) and 8 liver transplant recipients (LTR) transplanted recipients involved in a road cycling race (130 km) were compared with 35 healthy control subjects (HCS), also taking laboratory blood and urine tests the day before the race, at the end of the race, and 18 to 24 hours after competing. Results: The 3 groups showed similar race times (KTR, 5 hours 59 minutes \ub1 0 hours 39 minutes; LTR, 6 hours 20 minutes \ub1 1 hour 11 minutes; HCS, 5 hours 40 minutes \ub1 1 hour 28 minutes), similar short form (36) health survey scores, and similar trend of laboratory parameters which returned to baseline after 18 to 24 hours. After the race, there was an increase in creatinine (0.24 mg/dL; effect size [ES] = 0.78; P < 0.001), urea (22 mg/dL; ES = 1.42; P < 0.001), and a decrease of estimated glomerular filtration rate ( 1217 mL/min; ES = 0.85; P < 0.001). The increase of blood uric acid was more remarkable in HCS and KTR (2.3 mg/dL; ES = 1.39; P < 0.001). The KTR showed an increase of microalbuminuria (167.4 mg/L; ES = 1.20; P < 0.001) and proteinuria (175 mg/mL; ES = 0.97; P < 0.001) similar to LTR (microalbuminuria: 176.0 mg/L; ES = 1.26; P < 0.001; proteinuria: 213 mg/mL; ES = 1.18; P < 0.001), with high individual variability. The HCS had a nonsignificant increase of microalbuminuria (4.4 mg/L; ES = 0.03; P = 0.338) and proteinuria (59 mg/mL; ES = 0.33; P = 0.084). Conclusions: Selected and well-trained KTR and LTR patients can participate to an endurance cycling race showing final race times and temporary modifications of kidney function similar to those of HCS group, despite some differences related to baseline clinical conditions and pharmacological therapies. Patients involved in this study represent the upper limit of performance currently available for transplant recipients and cannot be considered representative of the entire transplanted population

Longitudinal Analysis of Cardiovascular Risk Factors in Active and Sedentary Kidney Transplant Recipients

Despite the benefits of physical activity on cardiovascular risk in kidney transplant recipients (KTRs), the long-term effects of exercise have been poorly investigated. This is a three-year observational study comparing graft function and cardiovascular risk factors in active KTRs (AKTRs) vs. sedentary KTRs (SKTRs). Methods: KTRs with stable renal function were assigned to active or sedentary group in relation to the level of daily physical activity based on World Health Organization (WHO) recommendations (<150 or >150 min/week, respectively). Complete blood count, renal function indices, lipid profile, blood pressure and anthropometric measures were collected yearly for an observation period of three years. The comparisons between the two groups were performed by repeated measures analyses of covariance (ANCOVAs), with age as a covariate. Results: Fifty-four subjects were included in the study. Thirty of them were identified as AKTRs (M/F 26/4, aged 45 \ub1 12 years) and 24 as SKTRs (M/F 18/6, aged 51 \ub1 14 years). Baseline characteristics were similar between the groups except body mass index (BMI) that was significantly higher in SKTRs (p = 0.043). Furthermore, over the three-year observation period, BMI decreased in AKTRs and increased in SKTRs (p = 0.006). Graft function was stable in AKTRs, while it showed a decline over time in SKTRs, as indicated by the rise in serum creatinine levels (p = 0.006) and lower eGFR (p = 0.050). Proteinuria, glucose and uric acid levels displayed a decrease in AKTRs and an increase in SKTRs during the three-year period (p = 0.015, p = 0.004 and p = 0.013, respectively). Finally, concerning lipid profiles, AKTRs had a significant reduction over time of triglycerides levels, which conversely showed a clinically relevant increase in SKTRs (p = 0.014). Conclusions: Our findings indicate that regular weekly exercise training may counteract the increased cardiovascular risks and also prevent graft function decline in KTRs

Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery

Membrane protein claudin3 has been recently suggested as a marker for biologically aggressive tumors and a possible target for the therapeutic delivery of active anti-cancer compounds. Claudin3-binding molecules such as the Clostridium perfringens enterotoxin (CPE), CPE-related molecules, and murine and chimeric antibodies have shown promising antitumor efficacy in preclinical oncological settings. We first engineered a fully human anti-claudin3 IgG1 antibody (IgGH6) by fusing the human IgG1 Fc-domain to the anti-claudin3 scFvH6 previously isolated from a pre-immune phage display library. The construct was expressed in mammalian cells and specifically targeted claudin3 endogenously expressed on the surface of different human ovarian cancer cell lines. No detectable cross-reactivity with other homologous claudins was observed. The epitope recognized by IgGH6 is located within the minor extracellular domain of claudin3 and becomes accessible only in tumor cells characterized by incomplete junction formation. Confocal microscopy experiments demonstrated that IgGH6 was actively internalized in tumor cells after binding to native claudin3 and co-localized, likely within intracellular vesicles, with the C-CPE peptide. Preliminary results indicate that IgGH6 accumulated in vivo in free claudin3 ovarian carcinoma xenografts. For its selective uptake in tumor cells and its human nature, IgGH6 represents a valuable candidate for antibody-drug conjugate therapeutic applications in ovarian cancer patients

Prostate Cancer in Renal Transplant Recipients: Results from a Large Contemporary Cohort

Objectives: The aim of this study was to assess the natural history of prostate cancer (PCa) in renal transplant recipients (RTRs) and to clarify the controversy over whether RTRs have a higher risk of PCa and poorer outcomes than non-RTRs, due to factors such as immunosuppression. Patients and Methods: We performed a retrospective multicenter study of RTRs diagnosed with cM0 PCa between 2001 and 2019. Primary outcomes were overall (OS) and cancer-specific survival (CSS). Secondary outcomes included biochemical recurrence and/or progression after active surveillance (AS) and evaluation of variables possibly influencing PCa aggressiveness and outcomes. Management modalities included surgery, radiation, cryotherapy, HIFU, AS, and watchful waiting. Results: We included 166 men from nine institutions. Median age and eGFR at diagnosis were 67 (IQR 60–73) and 45.9 mL/min (IQR 31.5–63.4). ASA score was >2 in 58.4% of cases. Median time from transplant to PCa diagnosis was 117 months (IQR 48–191.5), and median PSA at diagnosis was 6.5 ng/mL (IQR 5.02–10). The biopsy Gleason score was ≥8 in 12.8%; 11.6% and 6.1% patients had suspicion of ≥cT3 > cT2 and cN+ disease. The most frequent management method was radical prostatectomy (65.6%), followed by radiation therapy (16.9%) and AS (10.2%). At a median follow-up of 60.5 months (IQR 31–106) 22.9% of men (n = 38) died, with only n = 4 (2.4%) deaths due to PCa. Local and systemic progression rates were 4.2% and 3.0%. On univariable analysis, no major influence of immunosuppression type was noted, with the exception of a protective effect of antiproliferative agents (HR 0.39, 95% CI 0.16–0.97, p = 0.04) associated with a decreased risk of biochemical recurrence (BCR) or progression after AS. Conclusion: PCa diagnosed in RTRs is mainly of low to intermediate risk and organ-confined at diagnosis, with good cancer control and low PCa death at intermediate follow-up. RTRs have a non-negligible risk of death from causes other than PCa. Aggressive upfront management of the majority of RTRs with PCa may, therefore, be avoided

Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence

<p>Abstract</p> <p>Background</p> <p>Traditional prognostic factors in epithelial ovarian cancer (EOC) are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients.</p> <p>Methods</p> <p>MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome.</p> <p>Results</p> <p>MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p < 0.05). Moreover, multivariate analysis indicated that high expression levels of MGB-2 transcript (HR = 0.25, 95%, 0.08–0.75, p = 0.014) as well as positive immunostaining for the protein (HR = 0.41, 95%CI, 0.17–0.99, p = 0.048) had an independent prognostic value for disease-free survival.</p> <p>Conclusion</p> <p>This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can provide additional prognostic information about the risk of recurrence.</p

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas

QSAR Modeling: Where Have You Been? Where Are You Going To?

Quantitative Structure-Activity Relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss: (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists towards collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making