Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology

Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the bloodstream, hampering diagnosis through standard liquid biopsy procedures. Several tumors, as such as brain, kidney, prostate, and thyroid cancer, are in direct contact with other body fluids and may be alternative sources for cfDNA and ctDNA. Non-blood sources of cfDNA/ctDNA useful as novel oncologic biomarkers include cerebrospinal fluids, urine, sputum, saliva, pleural effusion, stool and seminal fluid. Seminal plasma cfDNA, which can be analyzed with cost-effective procedures, may provide powerful information capable to revolutionize prostate cancer (PCa) patient diagnosis and management. In the near future, cfDNA analysis from non-blood biological liquids will become routine clinical practice for cancer patient diagnosis and management

Como elaborar vinho de qualidade na pequena propriedade.

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Frequency of sleep bruxism behaviors in healthy young adults over a four-night recording span in the home environment

Objectives: This study aimed to assess frequency and multiple-night variability of sleep bruxism (SB) as well as sleep-time masticatory muscle activities (sMMA) in the home environment in healthy young adults using a portable device that provides electrocardiographic (ECG) and surface electromyographic (EMG) recordings from the masticatory muscles. Methods: The study was performed on 27 subjects (11 males, 16 females; mean age 28.3 ± 1.7 years) selected from a sample of healthy young students. Evaluation was carried out for four nights to record data on masticatory muscle activities using a compact portable device that previously showed an excellent agreement with polysomnography (PSG) for the detection of SB events. The number of SB episodes per sleep hour (bruxism index), and the number of tonic, phasic and mixed sMMA events per hour were assessed. A descriptive evaluation of the frequency of each condition was performed on all individuals, and gender comparison was investigated. Results: Mean sleep duration over the four recording nights was 7 ± 1.3 h. The average SB index was 3.6 ± 1.2. Most of the sMMA were tonic (49.9%) and phasic (44.1%). An ANOVA test showed the absence of significant differences between the four nights. No significant gender differences were detected for the SB index, phasic or tonic contractions; conversely, gender differences were detected for mixed sMMA events (p < 0.05). Conclusion: This investigation supports the concept that sMMA events are quite frequent in healthy adults. Differences over the four-night recording span were not significant. These data could be compared to subjects with underlying conditions that may lead to an additive bruxism activity and possible clinical consequences

Seasonal pattern in elderly hospitalized with acute kidney injury: a retrospective nationwide study in Italy

Purpose: Acute kidney injury (AKI) frequently complicates hospitalization and is associated with in-hospital mortality (IHM). It has been reported a seasonal trend in different clinical conditions. The aim of this study was to evaluate the possible relationship between seasons of the year and IHM in elderly hospitalized patients with AKI. Methods: We selected all admissions complicated by AKI between 2000 and 2015 recorded in the Italian National Hospital Database. ICD-9-CM code 584.xx identified subjects with age ≥ 65 years and age, sex, comorbidity burden, need of dialysis treatment and IHM were compared in hospitalizations recorded during the four seasons. Moreover, we plotted the AKI observed/expected ratio and percentage of mortality during the study period. Results: We evaluated 759,720 AKI hospitalizations (mean age 80.5 ± 7.8 years, 52.2% males). Patients hospitalized with AKI during winter months had higher age, prevalence of dialysis-dependent AKI, and number of deceased patients. In whole population IHM was higher in winter and lower in summer, while the AKI observed/expected ratio demonstrated two peaks, one in summer and one in winter. Logistic regression analysis demonstrated that parameters such as age, autumn, winter, comorbidity burden were positively associated with IHM. Conclusion: We conclude that a seasonality exists in AKI, however, relationship between seasons and AKI could vary depending on the aspects considered. Both autumn and winter months are independent risk factors for IHM in patients with AKI regardless of age, sex and comorbidity burden. On the contrary, summer time reduces the risk of death during hospitalizations with AKI

Home-Based Exercise in Elderly Patients with Claudication and Chronic Kidney Disease Is Associated with Lower Progressive Renal Function Worsening: A 5-Year Retrospective Study

This observational study aimed to monitor the 5-year trends of kidney function in patients with peripheral artery disease (PAD) and concomitant chronic kidney disease (CKD) enrolled or not enrolled into a rehabilitative exercise program. Sixty-six patients (aged 72 ± 10, males n = 52) at KDOQI stages III-IV and PAD at Rutherford’s stage I-III were included in the study, with a group (Exercise, EX; n = 32) receiving a 6-month structured pain-free home-based walking program and a group (Control, CO; n = 34) receiving walking advice and optimal nephrological care. Outcomes included kidney function measured through serum creatinine (sCr) and clinical outcomes, including the rate of advance of CKD stages and admission to dialysis, revascularizations, and hospitalizations. At baseline, the two groups were comparable for age, nephropathy, medications, comorbidities, and PAD severity. Patients in the EX group safely completed the exercise program. SCr values were slightly increased in EX (baseline: 2.35 ± 0.32; 5-year: 2.71 ± 0.39 mg/dL) and progressively worsened in CO (baseline: 2.30 ± 0.31; 5-year 4.22 ± 0.42 mg/dL), with a significant between-group difference (p = 0.002). The control group also showed a higher number of dialysis admissions (5 vs. 0, p = 0.025) and advancing CKD stage as well a higher risks for lower limb revascularization (hazard ratio: 2.59; 95%CI: 1.11–6.02; p = 0.027) and for all-cause hospitalization (hazard ratio: 1.77; 95%CI: 1.05–2.97; p = 0.031). PAD-CKD patients enrolled in a low-moderate intensity home-exercise program showed more favorable long-term trends in kidney function and clinical outcomes than patients with usual care. These preliminary observations need to be confirmed in randomized trials

Co-culture of hematopoietic stem/progenitor cells with human osteblasts favours mono/macrophage differentiation at the expense of the erythroid lineage

Hematopoietic stem cells (HSCs) are located in the bone marrow in a specific microenvironment referred as the hematopoietic stem cell niche, where HSCs interact with a variety of stromal cells. Though several components of the stem cell niche have been identified, the regulatory mechanisms through which such components regulate the stem cell fate are still unknown. In order to address this issue, we investigated how osteoblasts (OBs) can affect the molecular and functional phenotype of Hematopoietic Stem/Progenitor Cells (HSPCs) and vice versa. For this purpose, human CD34+ cells were cultured in direct contact with primary human OBs. Our data showed that CD34+ cells cultured with OBs give rise to higher total cell numbers, produce more CFUs and maintain a higher percentage of CD34+CD38- cells compared to control culture. Moreover, clonogenic assay and long-term culture results showed that co-culture with OBs induces a strong increase in mono/macrophage precursors coupled to a decrease in the erythroid ones. Finally, gene expression profiling (GEP) allowed us to study which signalling pathways were activated in the hematopoietic cell fraction and in the stromal cell compartment after coculture. Such analysis allowed us to identify several cytokine-receptor networks, such as WNT pathway, and transcription factors, as TWIST1 and FOXC1, that could be activated by co-culture with OBs and could be responsible for the biological effects reported above. Altogether our results indicate that OBs are able to affect HPSCs on 2 different levels: on one side, they increase the immature progenitor pool in vitro, on the other side, they favor the expansion of the mono/macrophage precursors at the expense of the erythroid lineage

Between Constraints and Coercion. Marriage and Social Reproduction in Northern and Central Italy, 18th-19th Centuries

In this paper we review the main theories of household and marriage systems, highlighting their inability to account for the astonishing variety of family and marriage patterns that characterized modern Italy. We propose a new interpretative framework, where social reproduction is given pride of place as the main factor shaping marital behavior and household formation in the past. We test our theory analyzing five populations in northern and central Italy, characterized by different ecological, economic, and social conditions. We use an event history analysis approach to model the timing of marriage in the populations under study. The results confirm that coercion mattered much more than Malthusian economic constraints. We conclude suggesting a more general application of our approach to the study of marital behavior, family formation, and residential patterns in the past

Maternal mortality in 19th- and early 20th-century Italy

Although dramatically reduced in Western and developed countries, maternal mortality is still today one of the most relevant social and health scourges in developing countries. This is the reason why high levels of maternal mortality are always interpreted as a sign of low living standards, ignorance, poverty and woman discrimination. Maternal mortality represents, therefore, a very peculiar characteristic of demographic systems of ancien regime. Despite this important role in demographic systems, no systematic study has been addressed to investigate the impact of maternal mortality in historical Italy. The aim of this article is to shed some light on such a phenomenon by investigating its trend over time and the determinants in some Italian populations between the 18th and the early 20th centuries. The analysis will make use of civil and parish registers linked together by means of nominative techniques, and it will be, therefore, carried out at the micro level

Investigation of asymmetrical shaft power increase during ship maneuvers by means of simulation techniques

Marine propulsion plants can experience large power fluctuations during tight maneuvers, with increases of shaft torque up to and over 100% of the steady values in straight course and considerable asymmetry between internal and external shafts during turning circle. This phenomenon (studied in Viviani et al 2007a and 2007b can be of particular interest for twin screw ships propulsion systems with coupled shaftlines, in which asymmetrical loads can represent a challenge for the whole propulsion system (e.g. unique reduction gear, shaftlines, automation). A joint research has been set up in order to deeply investigate the phenomenon, by means of large scale model testing and related numerical simulations. In the present work, preliminary simulation results with different simplified automation systems and with an automation system more similar to the real one are reported, allowing to get a better insight into this complex problem