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The association between environmental conditions and pregnancy outcome has been under investigation for a long time, but results appear to be inconclusive regarding damage to either the newborn or the mother. The aim of this study was to evaluate the distribution of hospitalization of newborns with low birthweight (

Background Effective screening for colorectal cancer can reduce mortality by early detection of tumours and colonic polyps. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a potential non‐invasive diagnostic tool for detection of cancer. The aim of this study was to evaluate the reliability of breath‐testing for colorectal cancer screening and early diagnosis using an advanced breath sampler. Methods The exhaled breath of patients with colorectal cancer and non‐cancer controls with negative findings on colonoscopy was collected using the ReCIVA® Breath Sampler. This portable device is able to capture the alveolar breath fraction without environmental contamination. VOCs were desorbed thermally and analysed by gas chromatography–mass spectrometry. The discriminatory ability of VOCs in detecting colorectal cancer was evaluated by receiver operating characteristic (ROC) curve analysis for each VOC, followed by cross‐validation by the leave‐one‐out method, and by applying stepwise logistic regression analysis. Results The study included 83 patients with colorectal cancer and 90 non‐cancer controls. Fourteen VOCs were found to have significant discriminatory ability in detecting patients with colorectal cancer. The model with the diagnosis of cancer versus no cancer resulted in a statistically significant likelihood of discrimination of 173·45 (P, Available screening methods for colorectal cancer have poor reliability and low patient compliance. Cancer cells produce altered metabolites, which are transported in the bloodstream and released in the alveoli; these volatile organic compounds (VOCs) can be detected in exhaled breath. This study used a new‐generation breath sampler, capable of selecting the alveolar fraction of the breath and preventing environmental contamination. A pattern of 14 VOCs was able to discriminate patients with colorectal cancer from healthy controls, with a true predictive value of 93 per cent, irrespective of cancer stage. Breath test signature in colorectal cancer

Italy was one of the nations most affected by SARS-CoV-2. During the pandemic period, the national government approved some restrictions to reduce diffusion of the virus. We aimed to evaluate changes in in-hospital mortality and its possible relation with patient comorbidities and different restrictive public health measures adopted during the 2020 pandemic period. We analyzed the hospital discharge records of inpatients from public and private hospitals in Apulia (Southern Italy) from 1 January 2019 to 31 December 2020. The study period was divided into four phases according to administrative restriction. The possible association between in-hospital deaths, hospitalization period, and covariates such as age group, sex, Charlson comorbidity index (CCI) class, and length of hospitalization stay (LoS) class was evaluated using a multivariable logistic regression model. The risk of death was slightly higher in men than in women (OR 1.04, 95% CI: 1.01–1.07) and was lower for every age group below the &gt, 75 years age group. The risk of in-hospital death was lower for hospitalizations with a lower CCI score. In summary, our analysis shows a possible association between in-hospital mortality in non-COVID-19-related diseases and restrictive measures of public health. The risk of hospital death increased during the lockdown period.

Caprine alphaherpesvirus 1 (CpHV-1) induces genital lesions in its natural host similar to those caused by Human alphaherpesvirus 2 (HHV-2), commonly named herpes simplex virus 2 (HSV-2) in human patients. CpHV-1 infection in goats could represent a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. PHA767491 is a potent inhibitor of HSV-1 and HSV-2, being able to limit replication of HHVs both in vitro and in the mouse model. In the present study the antiviral efficacy of PHA767491 against CpHV-1 was evaluated in vitro in MDBK cells. PHA767491 inhibited significantly CpHV-1 replication in a dose-dependent fashion by up to 2.50 log10 TCID50/50 μl and was able to decrease viral DNA by nearly 8 log10. These findings confirm that PHA767491 is highly effective not only against simplexviruses (HSV-1 and HSV-2), but also against the varicellovirus CpHV-1. Experiments will be necessary to assess whether PHA767491 is suitable for treatment of vaginal lesions in CpHV-1-goat model. This could provide hints for the therapy of genital alphaherpesvirus infections in humans.

Summary Introduction Few studies have investigated factors possibly related to the source of Helicobacter pylori infection in humans. Materials and methods This was a retrospective study including a population of 201 H. pylori positive patients and 259 H. pylori negative subjects observed at a tertiary referral center in Apulia. The H. pylori status was assessed by urea breath test. Data on socio-demographic characteristics and the consumption of different foods and beverages in the last year were collected by a questionnaire. Results No significant relationship was found between H. pylori infection and gender or age, type of employment, working in direct contact with the public, residence, level of education or exposure to pets. No association between H. pylori status and the consumption of fish, fruits, legumes, honey, spices, meats, milk and milk products including some typical product of our area was found. The same was true for the consumption of several kind of beverage including green tea and wine. Cigarette smoking and living in the same house with H. pylori positive relatives were significantly associated with H. pylori positivity. The intake of uncooked seafood (mussels and other molluscs) as well as some uncooked vegetables such as tomatos,pepper,and chicory,municipal water and the number of cups of coffee consumed per week correlated significantly with H. pylori status. The consumption of raw vegetables purchased from street vendors and the consumption of meals outside home were also associated with H. pylori infection. Conclusions Foods may represent an important route in the transmission of H. pylori among humans.

Canine parvovirus (CPV) is one of the most important cause of mortality in young dogs and no specific treatment exists. Since prolonged leukopenia greatly increases the risk of death in infected pups, strategies to counteract this decline were investigated. The outcomes of CPV naturally infected pups treated with the recombinant canine granulocyte-colony stimulating factor (rcG-CSF), in combination with the routine therapy, were compared with similarly-managed infected pups not treated with rcG-CSF. A non-randomized prospective clinical trial was performed on 62 CPV infected pups with WBC counts

Autism Spectrum Disorder (ASD) has historically been studied, known, and diagnosed in males. Females tend to remain unidentified, especially those with average intelligence abilities. This sex/gender difference might be partially explained by biological risk factors, but it is probably also bound to methodological issues. The present study aims to examine phenotypic characteristics (cognitive, emotive, socio-communicative, and academic) of a group of 54 females with ASD matched to a group of 55 males with ASD (3–18 years), all without cognitive impairment. Results suggest that there are subtle, yet potentially meaningful, quantitative, and qualitative phenotypic differences between females and males that common screening tests are not always sensitive enough to recognize. Further studies to improve practice and course for the assessment of females, reducing sex/gender-based inequities in ASD care, are required.

Introduction Pressure support ventilation (PSV) should allow spontaneous breathing with a “normal” neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of “Low” and/or “High” neuro-ventilatory drive during clinical application of PSV. Method In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with “Normal” (EAdiPEAK 5–15 μV), “Low” (EAdiPEAK PEAK > 15 μV) neuro-ventilatory drive. Results Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdiPEAK, was “Low” in 50.116 breath (28%), “Normal” in 88.419 breaths (50%) and “High” in 38.582 breaths (22%). The average times spent in “Low”, “Normal” and “High” class were 1.37, 3.67 and 0.55 h, respectively (p Conclusions We observed wide variations in EAdi amplitude and unevenly distributed “Low” and “High” neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

The emergence of link between periodontal disease and diabetes has created conditions for analyzing new interdisciplinary approach making toward tackling oral health and systemic issues. As periodontal disease is a readily modifiable risk factor this association has potential clinical implications. The aim of this paper was systematically review the extant literature related to analytics data in order to identify the association between type 1 diabetes (T1DM) in childhood and adolescence with periodontal inflammation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a database search between 2004 and 2019. A manual search of the literature was conducted as an additional phase of the search process, with the aim of identifying studies that were missed in the primary search. One hundred and thirty-nine records were screened and 10 fulfilled the inclusion criteria. Most studies were of moderate methodological quality. Outcomes included assessments of diabetes and periodontal status. In diabetic populations, compared to healthy subjects, interindividual differences in periodontal status are reflected in higher severity of periodontal inflammation. The most reported barriers to evidence uptake were the intrinsic limits of cross-sectional report data and relevant research, and lack of timely research output. Based on the evidence presented within the literature, the aforementioned biomarkers correlate with poor periodontal status in type 1 diabetic patients. Whilst the corpus of the evidence suggests that there may be an association between periodontal status and type 1 diabetes, study designs and methodological limitations hinder interpretation of the current research.

Food ice is used as an ingredient or as a coolant in drinks and in the storage of food, especially fishery products. Studies show that ice can be polluted both by chemical substances and by bacteria and fungi. In particular, the presence of fungi in these food matrices has acquired an important role in Public Health, as it can represent a risk factor for fungal complications in immunocompromised subjects. In the present study we evaluated the hygiene&ndash, sanitary quality of food ice from public and collective catering establishments in a large area of Southern Italy, investigating the mandatory parameters (Escherichia coli, coliform and Enterococci) and some accessory parameters (Staphylococcus aureus, Pseudomonas aeruginosa and fungi) provided for Italian Legislative Decree 31/01. Although 54.5% of samples were compliant, the results highlight a vast contamination of food ice by bacteria and fungi. In particular, 95.8% of samples were contaminated by fungi, stressing no difference between compliant and non-compliant samples. Their presence is generally attributable to the poor sanitation conditions in the production and/or administration phase and to the incorrect sanitization and ordinary maintenance procedures. It seems appropriate to suggest the need to carry out a specific risk assessment with respect to the self-control plans.

Strongyloidiosis by Strongyloides stercoralis is a disease of increasing interest in human and animal medicine. The scientific knowledge on canine strongyloidiosis is hindered by the poor diagnostics available. To assess the most sensitive and specific diagnostic method, feces and blood from 100 shelter dogs were screened for S. stercoralis by coprological, molecular and serological tests. Thirty-six dogs (36%) scored positive to S. stercoralis by coprology (22.3% to Baermann) and/or 30% to real time-polymerase chain reaction (rt-PCR). According to two composite reference standards (CRS) based on all coprological methods and rt-PCR (first CRS) or in combination with serology (second CRS), the most sensitive test was IFAT (93.8%; CI 82.8–98.7), followed by rt-PCR (80.6%; 95% CI 64–91.8) and Baermann (60.6%; 95% CI 42.1–77.1). The inconsistent shedding of L1 during the 4-week follow-up in infected dogs suggests the importance of multiple faecal collections for a reliable diagnosis. A combination of serological and coprological tests is recommended for the surveillance and diagnosis of S. stercoralis infection in dogs.

Since Hans Asperger’s first description (Arch Psych Nervenkrankh 117:76–136, 1944), through Lorna Wing’s translation and definition (Psychol Med 11:115–129, 1981), to its introduction in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM, 1994), Asperger Syndrome has always aroused huge interest and debate, until vanishing in the DSM fifth edition (2013). The debate regarded its diagnostic validity and its differentiation from high functioning autism (HFA). The present study aimed to examine whether AS differed from HFA in clinical profiles and to analyze the impact of DSM-5’s innovation. Differences in cognitive, language, school functioning and comorbidities, were revealed when 80 AS and 70 HFA patients (3–18 years) were compared. Results suggested that an AS empirical distinction within autism spectrum disorder should be clinically useful.

Background: Luteinizing hormone (LH) is essential for normal follicular development and oocyte maturation. In particular, fluctuations of LH during the follicular phase have a significant impact on morphological and functional changes of the oocyte and determine its meiotic status and ability to be fertilized. Objective: This prospective randomized controlled trial examined effects of endogenous follicular phase LH levels on oocyte maturity and IVF outcomes in fixed vs. flexible in vitro fertilization. Materials and Methods: Normo-ovulatory women age

Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.

Background: Short-term exposure to air pollution, as well as to climate variables could be linked to a higher incidence of respiratory viral diseases. The objective of the study is to assess the short-term impact of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the initial outbreak. Methods: The daily number of COVID19 cases in Lombardy from February 25th to March 10th 2020, and the daily average concentrations of particulate matter (PM10, PM2·5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity – RH%, wind speed, precipitation), were analyzed. A mixed model with a logarithm transformation as link function was applied to evaluate the relationship between all the variables. Additionally, change points (Break Points; BP) in the relationship between incident cases and air pollution or climatic factors were estimated. Findings: The analysis showed a two-phase effect of PM10 on COVID19 incidence, with a negative association at the beginning of the examined period and a positive one later on, while a positive relationship was observed for O3. The COVID19 spread in Lombardy showed to be influenced positively by RH%, and negatively by wind speed. A BP at 40 µg/m3 was observed for PM10 at lag8, and for O3 at lags 3-8 and 10. Interpretation: PM10, O3, RH% and wind speed showed a short-term association with the COVID19 incidence. Air pollution and climate conditions should be considered as part of an integrated approach when containment measures against SARS-CoV-2 are adopted. Funding: The study did not receive any fund. Declaration of Interests: The Authors declare no conflict of interest.

The prevalence data of Leishmania infantum infection in cats are characterized by a large variability mainly attributed to the differences in diagnostic techniques. In the absence of consensus about the method of choice for diagnosing feline leishmaniosis, the performance of a new immunofluorescence antibody test (IFAT) was herein analytically described by the comparison with IFAT commonly used for the diagnosis of canine leishmaniosis (i.e., IFAT-OIE) and a laboratory enzyme-linked immunosorbent assay (ELISA). Sera of cats living in visceral leishmaniosis–endemic (n = 105) and visceral leishmaniosis–non-endemic (n = 50) areas were tested by the above methodologies and real-time PCR (qPCR). The most frequent result was represented by triple negativity to the three tests (IFAT-OIE, ELISA, and qPCR) in 42.9% and 80% cats from endemic and non-endemic areas, respectively. Bayes latent class analysis gave an output probability of 34.1% (posterior standard deviation, psd = 5.4%) of true L. infantum cases (TCL) which represent the true estimated prevalence of infection. The sensitivity of each variable contributing to define the TCL was 24% (psd = 6.3%) for qPCR, 78.8% (psd = 8.7%) for ELISA and 91.8% (psd = 5.2%) for IFAT-OIE. The probability to be a TCL was 94.5% for the sample from an endemic area. The cross-validation of the new IFAT by a logistic model correctly identified as positive 80.7% of subjects defined as TCL and negative 89.9% as not TCL, respectively, by the Bayesian model. The study results estimate a good accuracy of the IFAT in predicting cats exposed to L. infantum. Therefore, this procedure may be beneficial for screening cat populations for a better understanding of the epidemiology of feline leishmaniosis.

Osteoarthritis (OA) is a chronic disease that requires a multimodal therapeutic approach. The aim of this study was to evaluate the effects of undenatured type II collagen (UC-II) as compared to robenacoxib in dogs affected by OA. Our hypothesis was that the two compounds would be similar (non-inferiority) in improving mobility. To test this hypothesis, a complete orthopedic examination, x-ray and the Liverpool Osteoarthritis in Dogs (LOAD) survey were performed in dogs affected by OA before and after the treatments. The study was designed as a clinical, randomized, controlled and prospective study. Sixty client-owned dogs were randomized in the R group (n = 30, robenacoxib 1 mg/kg/day for 30 days) and in the UC-II group (n = 30, UC-II 1 tablet/day for 30 days). Thirty days after the beginning of the treatment (T30), the dogs were reassessed for the LOAD, MOBILITY and CLINICAL scores. Based on the data obtained from the study, a significant reduction in LOAD and MOBILITY scores was recorded between T0 and T30 with a similar magnitude among the two groups (R = 31.5%, p &lt, 0.001, UC-II = 32.7%, p = 0.013). The results of this study showed that UC-II and robenacoxib were able to similarly improve mobility of dogs affected by OA.

Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p, Author summary Zoonotic visceral leishmaniasis is a potentially fatal parasitic disease, which is caused by Leishmania infantum. Its distribution is associated with the occurrence of the sand fly vectors and reservoir hosts. Since L. infantum infection can occur in cats with clinical or subclinical outcomes, the role of cats in the epidemiology of zoonotic visceral leishmaniasis needs to be thoroughly assessed. This study aimed to evaluate the prevalence and associated risk factors for infection with L. infantum in a large subset of cats across Italy, a known endemic area with records of human cases of visceral leishmaniasis. Serum and blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum and parasites’ DNA, respectively. A cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or real-time PCR (0.8%). The risk of L. infantum infection in cats was associated to the geographical areas, age class, neutering status and feline immunodeficiency virus infection. These findings reveal that cats are exposed to and/or infected by this protozoan across the country, warranting further investigation to assess their role in the epidemiology of zoonotic visceral leishmaniasis to refine surveillance and prevention strategies against this veterinary and medically important ailment.

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lock-down measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity – RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2.

To evaluate, in patients stimulated with recombinant FSH and GnRH antagonists, whether triggering the final maturation of oocytes affects IVF outcomes.Five hundred and six IVF procedures were divided into three groups according to the timing of hCG administration: when at least 2 follicles reached the diameter of 17 mm, at least 2 follicles reached 18 mm and at least 2 follicles reached 20 mm. The main outcome was the number of mature oocyte that was the dependent variable of a multivariate model whose independents were, age, AFC, hCG timing, E2 levels at hCG day, number of follicles in different categories of dimension. Secondary endpoints were to compare fertilization, implantation and pregnancy rates in a multilevel multivariate model whose covariates were age, BMI, AFC, embryo quality and cause of infertility.Timing did not result a statistically significant factor influencing the number of oocytes collected, which was influenced by age, AFC, number of follicles between 12.1 and 15.9 mm and E2 levels. Implantation rate and pregnancy rate appear to be affected only by embryo quality.The number of oocytes collected and the probability of pregnancy are not associated with the time of hCG administration.

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD.

Purpose High-flow oxygen therapy delivered through nasal cannulae improves oxygenation and decreases work of breathing in critically ill patients. Little is known of the physiological effects of high-flow oxygen therapy applied to the tracheostomy cannula (T-HF). In this study, we compared the effects of T-HF or conventional low-flow oxygen therapy (conventional O2) on neuro-ventilatory drive, work of breathing, respiratory rate (RR) and gas exchange, in a mixed population of tracheostomized patients at high risk of weaning failure. Methods This was a single-center, unblinded, cross-over study on fourteen patients. After disconnection from the ventilator, each patient received two 1-h periods of T-HF (T-HF1 and T-HF2) alternated with 1 h of conventional O2. The inspiratory oxygen fraction was titrated to achieve an arterial O2 saturation target of 94–98% (88–92% in COPD patients). We recorded neuro-ventilatory drive (electrical diaphragmatic activity, EAdi), work of breathing (inspiratory muscular pressure–time product per breath and per minute, PTPmusc/b and PTPmusc/min, respectively) respiratory rate and arterial blood gases. Results The EAdipeak remained unchanged (mean ± SD) in the T-HF1, conventional O2 and T-HF2 study periods (8.8 ± 4.3 μV vs 8.9 ± 4.8 μV vs 9.0 ± 4.1 μV, respectively, p = 0.99). Similarly, PTPmusc/b and PTPmusc/min, RR and gas exchange remained unchanged. Conclusions In tracheostomized patients at high risk of weaning failure from mechanical ventilation, T-HF did not improve neuro-ventilatory drive, work of breathing, respiratory rate and gas exchange compared with conventional O2 after disconnection from the ventilator. The present findings might suggest that physiological effects of high-flow therapy through tracheostomy substantially differ from nasal high flow.

Background The physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure. Methods This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88–92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded. Results EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 μV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 μV during HFNC2 (conventional O2: p

The Acute Respiratory Distress Syndrome Network protocol recommends limiting tidal volume and plateau pressure; it also recommends increasing respiratory rate to prevent hypercapnia. We tested a strategy that combines the low tidal volume with lower respiratory rates and minimally invasive CO2 removal.Ten lung-damaged pigs (instilled hydrochloride).Two conditions randomly applied in a crossover fashion: the Acute Respiratory Distress Syndrome Network protocol and the Acute Respiratory Distress Syndrome Network protocol plus lower respiratory rate plus minimally invasive Co2 removal. A similar arterial Co2 partial pressure was targeted in the two conditions.Physiological parameters, computed tomography scans, plasma and bronchoalveolar lavage concentrations of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-α. During the lower respiratory rate condition, respiratory rate was reduced from 30.5 ± 3.8 to 14.2 ± 3.5 (p0.01) breaths/min and minute ventilation from 10.4 ± 1.6 to 4.9 ± 1.7 L/min (p0.01). The extracorporeal device removed 38.9% ± 6.1% (79.9 ± 18.4 mL/min) of CO2 production. During the lower respiratory rate condition, interleukin-6, interleukin-8, and tumor necrosis factor-α concentrations were significantly lower in plasma; interleukin-6 and tumor necrosis factor-α concentrations were lower in bronchoalveolar lavage, whereas the concentrations of the other cytokines remained unchanged.The strategy of lower respiratory rate plus minimally invasive extracorporeal CO2 removal was feasible and safe and, as compared with the Acute Respiratory Distress Syndrome Network protocol, reduced the concentrations of some, but not all, of the tested cytokines without affecting respiratory mechanics, gas exchange, and hemodynamics.

Postoperative infections are a concern, especially in total knee and total hip arthroplasty. We evaluated the air quality in orthopaedic operating theatres in southeastern Italy to determine the level of bacterial contamination as a risk factor for postoperative infection. Thirty-five hospitals with operating theatres focused on total knee and total hip arthroplasty participated. We sampled the air passively and actively before surgeries began for the day (at rest) and 15 min after the surgical incision (in operation). We evaluated bacterial counts, particle size, mixed vs turbulent airflow systems, the number of doors, number of door openings during procedures and number of people in the operating theatre. We found no bacterial contamination at rest for all sampling methods, and significantly different contamination levels at rest vs in operation. We found no association between the number of people in the surgical team and bacteria counts for both mixed and turbulent airflow systems, and low bacterial loads, even when doors were always open. Overall, the air quality sampling method and type of ventilation system did not affect air quality.

Background: Cancer Antigen 15-3 (CA 15-3) is a tumor-associated antigen used as serum marker for breast cancer surveillance in patients and for monitoring the response to treatment. Aim of this study was to retrospectively evaluate CA 15-3 as a prognostic factor in early detection of breast cancer relapse as well as to analyze the statistical correlation between CA 15-3 levels and clinical-pathological parameters including staging, grading, estrogen and progesterone receptors. Methods: Sera of 726 women with breast carcinoma obtained preoperatively and postoperatively were assayed for CA 15- 3 by chemoluminescent immunometric assay. Results: We found that the mean serum CA 15-3 levels in patients before surgery were significantly higher (36.59 U/ml) compared with those of CA 15-3 after surgery (27.11 U/ml). We also found that elevated preoperative serum levels of CA 15-3 were significantly correlated with the presence of metastatic disease. In particular, among 305/700 patients (43,6%) that displayed over cut-off (>40U/ml) preoperative levels of CA 15-3, 94 patients (30,8%) developed advanced disease (metastases to distant sites). By contrast, in a subgroup of 395/700 patients (56.4%) with CA 15.3 serum levels < 40U/ml, only 32/305 patients (8%) showed signs of advanced disease during follow-up. Cox regression analysis revealed that only the presence of metastasis and the increased serum levels of CA 15-3 after surgery are significant risk factors for relapse of disease. Conclusion: Elevated preoperative concentrations of CA 15-3 may be a useful predictive factor for cancer progression in postoperative patients.

This study represents the first investigation of microbiological groundwater pollution as a function of aquifer type and season for the Apulia region of southern Italy. Two hundred and seven wells were randomly selected from those monitored by the Regional Agency for Environmental Protection for emergency use. Both compulsory (Escherichia coli, Total Coliform, and Enterococci) and optional (Pseudomonas aeruginosa, Salmonella spp., Heterotrophic Plate Count at 37 and 22 °C) microbiological parameters were assessed regularly at these wells. Groundwater from only 18 of the 207 (8.7 %) wells was potable; these all draw from karst-fissured aquifers. The remaining 189 wells draw from karst-fissured (66.1 %) or porous (33.9 %) aquifers. Of these, 82 (43.4 %) tested negative for Salmonella spp. and P. aeruginosa, while 107 (56.6 %) tested positive for P. aeruginosa (75.7 %), Salmonella spp. (10.3 %), or for both Salmonella spp. and P. aeruginosa (14 %). A logistic regression model shows that the probability of potable groundwater depends on both season and aquifer type. Typically, water samples were more likely to be potable in autumn-winter than in spring-summer periods (odds ratio, OR = 2.1; 95 % confidence interval, 95 % CI = 1.6-2.7) and from karst-fissured rather than porous aquifers (OR = 5.8; 95 % CI = 4.4-7.8). Optional parameters only showed a seasonal pattern (OR = 2.6; 95 % CI = 1.7-3.9). Clearly, further investigation of groundwater microbiological aspects should be carried out to identify the risks of fecal contamination and to establish appropriate protection methods, which take into account the hydrogeological and climatic characteristics of this region.

Caprine herpesvirus 1 (CpHV-1) infection in goats is responsible for genital lesions resembling the lesions induced by herpesvirus 2 in humans (HHV-2). The immunosuppressive drug Mizoribine (MIZ) is able to increase the antiviral activity of Acyclovir (ACV) against herpesvirus infections, raising interesting perspectives on new combined therapeutic strategies. In this study the anti-CpHV-1 activity in vitro of ACV alone or in combination with MIZ was evaluated. ACV (100μg/ml) displayed an antiviral effect on CpHV-1 replication. This inhibitory effect was higher when ACV (100μg/ml) was used in association with MIZ (20μg/ml). Other combinations of ACV and MIZ in various concentrations were not as effective as ACV 100μg/ml/MIZ 20μg/ml. These findings suggest that the association of ACV and MIZ is potentially useful for treatment of genital infection by herpesviruses.

To evaluate the relationship between sperm nuclear vacuoles and sperm morphology and to investigate the influence of the rate of spermatozoa with head vacuolization (SVR) in a seminal sample on the clinical outcomes in couples undergoing intracytoplasmic sperm injection.26 patients undergoing infertility investigations were included and were divided in two groups according to an SVR ≤ 20,28 % (Group A) or 20,28 % (Group B), and were investigated to verify the influence of SVR on the fertilization rate, embryo quality, pregnancy and implantation rates.Abnormal spermatozoa with nuclear vacuoles were significantly higher (p 0.001) than the percentage of normal spermatozoa with nuclear vacuoles. Patients in group A had a percentage of abnormal sperm with nuclear vacuole significantly lower compared to group B (p 0,001), but there was no difference in the percentage of normal sperm with nuclear vacuoles. Fertilization rates and the number of top quality embryos did not differ between the two groups. The pregnancy and implantation rates were significantly higher in Group A compared to Group B (respectively p 0,05 and p 0.001).For the first time, we propose a cut off value in the proportion of sperms with nuclear vacuolization on the total of sperm in seminal samples, and demonstrate a relationship between SNV and clinical outcomes after ICSI. The SNV rate could be introduced as an easy diagnostic evaluation prior to perform an ICSI cycle.

RATIONALE: In the presence of increased chest wall elastance, the airway pressure does not reflect the lung-distending (transpulmonary) pressure. OBJECTIVE: To compare the physiological effects of a conventional open lung approach titrated for an end-inspiratory airway opening plateau pressure (30 cm H2O) with a transpulmonary open lung approach titrated for a elastance-derived end-inspiratory plateau transpulmonary pressure (26 cm H2O), in a pig model of acute respiratory distress syndrome (HCl inhalation) and reversible chest wall mechanical impairment (chest wall and abdomen restriction). METHODS: In eight pigs, physiological parameters and computed tomography were recorded under three conditions: 1) conventional open lung approach, normal chest wall; 2) conventional open lung approach, stiff chest wall; and 3) transpulmonary open lung approach, stiff chest wall. MEASUREMENTS AND MAIN RESULTS: As compared with the normal chest wall condition, at end-expiration non aerated lung tissue weight was increased by 116 ± 68% during the conventional open lung approach and by 28 ± 41% during the transpulmonary open lung approach (p < .01), whereas cardiac output was decreased by 27 ± 19% and 22 ± 14 %, respectively (p = NS). CONCLUSION: In this model, the end-inspiratory transpulmonary open lung approach minimized the impact of chest wall stiffening on alveolar recruitment without causing hemodynamic impairment

Background/purpose According to WHO recommendations, 12-year-olds are considered an important target group for evaluating the level of dental caries among children with permanent teeth, and are often chosen for international comparisons. The aim of the present study was to evaluate the current oral health status of 12-year-old children in southeast Italy, stratified by gender and residential area. Materials and methods The survey was conducted on 431 children enrolled by multistage cluster sampling. A dental caries experience index (decayed, missing, and filled permanent teeth; DMFT) was recorded at schools by a team of examiners trained at the start of the study. Statistical analyses by Chi-square, Fisher's exact, and Wilcoxon tests were performed using SAS version 9.1 software for PCs. We applied the Zero-Inflated Negative Binomial regression model in the STATA package. Results Caries prevalence was recorded in 38.3% of the sample. Estimated means and 95% confidence intervals of the DMFT index by gender were: 1.15 (0.91–1.39) for males, 1.26 (1.02–1.5) for females, and 1.21 (1.03–1.39) for the total sample. The D component of the index was dominant. The mean number of caries found in southeast Italy was significantly higher than the national mean (t = 3.125, P = 0.002), but significantly lower than the mean for south Italy (t = −2.125, P = 0.03). Results of the regression model showed that only the mother and father's nationality and educational level contributed to the DMFT. Conclusions The oral health situation of 12-year-old children from southeast Italy seems to be in line with that in other Western European countries.

The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost-benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA-IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA-IC in 103 patients with HCV chronic infection. Serum HCV-RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA-IC levels were higher in responders (238 AU, interquartile difference 130-556 AU) and decreased significantly to 125 AU (70-290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI 1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti-HCV positive patients undergoing antiviral therapy.

Neurofunctional effects produced by gestational all-trans retinoic acid (all-trans RA) treatment were investigated in the offspring of Sprague-Dawley rats. Reproduction data, onset of reflexive behavior, locomotor activity, motor coordination and motor learning were examined. Moreover, possible changes in size and morphology of the cerebellum were evaluated. The results show that all-trans RA treatment (2.5 mg/kg, by gavage) on gestational days (GD) 11-13 significantly increased postnatal mortality and decreased pup weight gain. Moreover, all-trans RA-treated rats showed a significant delay in eyes opening, hair growth as well as in the maturation of righting reflex, cliff aversion and pole grasping. All-trans RA treatment significantly impaired the ambulatory activity in adult rats without altering the number of rearings. All-trans RA-treated rats subjected to the rotarod/accelerod task showed significant impairment in both motor coordination and motor learning ability. The morphological analysis revealed a significant reduction in the cerebellar size and impairment in foliation profile, at PND 3 with subsequent recovery at PNDs 8 and 40. The evidence that functional alterations increase with age and persist in adulthood whereas the morphological changes decline with age, strongly supports the view that, besides the cerebellum morphology, the organization of the cerebellar circuitry, and in particular of cortico-cerebellar connections, are also affected by all-trans RA treatment.

Hepatocellular carcinoma (HCC) growth severely affects prognosis. Ki-67, a known marker of cell proliferation, is a negative prognostic factor in HCC. Growth factors such as the epidermal growth factor (EGF) induce HCC cell proliferation but do not explain the great heterogeneity of HCC growth. Laminin-5 (Ln-5) is an extracellular matrix protein (ECM) present in the tissue microenvironment of HCC. The two main receptors for Ln-5, integrins α3β1 and α6β4, are expressed on the cell surface of HCC cells. The aim of this study is to investigate an alternative mechanism of HCC growth whereby Ln-5 promotes HCC cell proliferation through α3β1 and α6β4. HCC tissues containing Ln-5 display a larger diameter and higher number of positive cells for Ki-67, a well known proliferative index, as determined by double immunofluorescence staining and real-time PCR on microdissected tissues. In vitro, Ln-5, but not collagen I, collagen IV or fibronectin, induces proliferation as much as EGF does, via Erk phosphorylation as a consequence of β4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite β4 integrin and Erk1/2 activation. After transfection with α3 integrin, in the presence of Ln-5 one of these HCC cell lines acquires a proliferative activity whereas one of the proliferative HCC cell lines, knocked-down for α3 integrin, loses its proliferative activity. Conclusions: Our study suggests a new mechanism of HCC growth whereby Ln-5 stimulates proliferation via a different function of α6β4 and α3β1. (HEPATOLOGY 2007.)

To assess the performance of different ovarian reserve tests for predicting the total numbers of oocytes retrieved and mature oocytes.A retrospective study was performed on 71 women undergoing their first IVF/intracytoplasmic sperm injection treatment. Basal ovarian reserve screening was performed on days 2-3 of a spontaneous cycle. Patients were down-regulated with the GnRH agonist, whereas ovarian stimulation was carried out with recombinant FSH, starting from day 2 to 3 of the cycle. The main outcome measures were the numbers of oocytes retrieved and mature oocytes.The total number of oocytes was positively correlated with AFC (p0.0001) and E(2) levels post-GnRH (p0.004), whereas there was an inverse correlation with age (p0.0001). The number of mature oocytes also correlated with AFC (p0.008) and E(2) levels post-GnRH (p0.009), and inversely with age (p0.0004). Univariate linear regression of square root of number of oocytes (SQNO) shows that acceptable predictors of number oocytes, based on model significance and R(2) are AFC (R(2)=0.215), age (R(2)=0.24) and E(2) variation (R(2)=0.09). The following model is proposed to predict the number of mature oocytes: ln(MO)=ln(NO)-2.09+0.028 AGE+0.03 BMI.The number of antral follicles and patient age appear to be good markers of ovarian response in IVF treatments. Additional information is provided by stimulated E(2) levels.

Endometriosis is an estrogen-correlated benign disease characterized by a marked ability of endometrial-like cells to invade and proliferate outside uterine cavity, resembling for some invasive aspect the cancer growth. The molecular mechanisms regulating endometrial cell invasiveness are mostly unknown, although interactions between extracellular matrix (ECM) proteins and their transmembrane receptors, integrins, are likely to play a central role. In particular, laminin (Ln)-5 could be closely involved, as it is in cancer. We have investigated the expression of Ln-1, Ln-5, and collagen IV (Coll IV) ECM proteins and their receptors, alpha3beta1 and alpha6beta4 integrins, in atrophic, proliferative, and secretive endometrium and in endometriosis. The results show that Ln-5, but not Ln-I and Coll IV, is altered in secretive endometrium as well as in endometriosis tissues. No alterations are observed in atrophic or proliferative endometrium. Consistently, the polarization of both integrin subunits alpha3 and beta1, but not alpha6 and beta4, is altered in secretive endometrium and endometriosis tissues, but not in atrophic and proliferative endometrium. These results seem to suggest that Ln-5 and alpha3beta1 could be involved in the invasive mechanism of endometriosis. The altered expression of Ln-5, by upregulating matrix metalloproteases activity, suggest an invading process similar to that of many cancer processes.

Background The increase in costs related to the diagnosis and treatment of chronic-degenerative diseases requires a better knowledge of the true care pathway of patients. The study objective was to explore, using multi-state modeling, how analyses of drug prescriptions and data obtained from hospital discharge sheets can be used in combination to build a model of patients health care pathway in a non experimental setting. The model was applied to Chronic Obstructive Pulmonary Disease (COPD). Methods Based on the GOLD guidelines, access to hospitalization for COPD and prescription pharmaceuticals were awarded to seven transients states theoretically progressive. The intensity of transition were estimated with the non-parametric method proposed by Aalen and Johansen for multi-state Markov models non-homogeneous in time. Results The COPD patients included in the study are 111190. Patients admitted with a diagnosis of non acute COPD had a growing probability over time of needing prescriptions for inhaled corticosteroids (ICS) or the set combination of long-acting beta-agonists (LABA) and ICS; they also had a rising probability of an exacerbation. The use of ICS alone or in combination with LABA delays a hospital admission for acute respiratory failure by about 6 months, as compared to short-acting beta-agonists or anticholinergics. Conclusion The probabilities of a transition and their distribution in relation to time, sex, age and clinical status can be a helpful tool for those operating in the health care sector, who are called upon to carry out decisions from the standpoints of both efficacious clinical management and an efficient use of resources.

The purpose of this study was to evaluate the prevalence of intestinal parasites in 277 healthy subjects in the city of Mamuras (Albania, South Eastern Europe) and the correlation between parasitic infections and possible risk factors. Faecal samples collected with sodium-acetate-formalin fixative were concentrated by formalin ethylacetate sedimentation and examined as wet mounts, permanent stains and by anti-Giardia/Cryptosporidium fluorescent antibodies. Data concerning age, sex, level of education, availability of piped water, number of people living in the same house, and residence in rural or urban area were collected for each subject. Statistical analysis was performed by chi-square test and regression logistic analysis. The overall prevalence of intestinal parasites was 183/277 (66.06%). In particular, pathogenic protozoa or helminths were found in 67 subjects (24.18%), including Trichuris trichiura in 34 (12.27%), Giardia duodenalis in 31 (11.19%), Hymenolepis nana in 5 (1.8%), Ascaris lumbricoides in 3 (1.08%). A significant correlation was observed only between parasite colonization and older age and between Trichuris trichiura infection and residence in rural areas.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Because of its increased incidence in the last decade and the estimated further increase in the next 2 decades, HCC is arousing great interest. In Europe and North America, it commonly develops on cirrhotic livers, and surveillance programs have therefore been suggested to identify early HCC, at a stage when it remains suitable for surgical therapy and has a better clinical outcome. The only serologic marker used in clinical practice is alpha-fetoprotein (alpha-FP), but its sensitivity is poor. In our study, 120 patients with HCC and 90 patients with liver cirrhosis were investigated. We report for the first time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specificity (48.9%). However, the combination of alpha-FP and SCCA yielded a correct serologic diagnosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specificity of SCCA. In conclusion, the combined use of alpha-FP and SCCA antigen represents a more powerful tool for the serologic detection of HCC.

The occurrence of metastasis severely affects prognosis and survival of breast cancer patients. In order to metastasize, breast cancer cells need to cross the basement membrane (BM) tissue boundaries. Matrix metalloproteases (MMPs) are enzymes with proteolytic activity towards extracellular matrix components (ECM) of the BM, that are blocked by physiological tissue inhibitors (TIMPs). Cancer metastasis occurs as a result of an imbalance between MMPs, in particular MMP-2 and MMP-9, and TIMPs, in particular TIMP-2 and TIMP-1. This is the first study to report that pro-MMP-9 and TIMP-1 serum concentrations are inversely correlated in breast cancer patients. In the same patients, we determined the pro-MMP-9, the TIMP-1, the pro-MMP-2 and TIMP-2 before and after surgical eradication of the breast cancer. Our results show that after surgery, when the breast cancer tissue was removed, pro-MMP-9 concentrations dramatically decreased and TIMP-1 concentrations strongly increased, with statistically significant differences, so that a new balance was established. No statistically significant differences were observed regarding pro-MMP-2 and TIMP-2. Also, no correlation was found between pro-MMP-2, pro-MMP-9, TIMP-1 and TIMP-2 and a number of clinical and pathological parameters. In conclusion, our study suggests that pro-MMP-9 and TIMP-1 could be used as markers of disease during the follow-up of breast cancer patients and possibly as prognostic markers, although more studies are needed to address this issue.

Background: Acute coronary syndrome is a major cause of death, morbidity and access in emergency departments (ED). Methods: We evaluated a point-of-care testing (POCT) for the determinations of cardiac markers in an emergency department (ED), defining the clinical efficiency (management of patient with chest pain) and economic effectiveness (rationalization of preanalytical phase) related to data of Core Lab. Results: The results of analytical performances showed a good correlation (cTnI r2=0.89, myoglobin r2=0.84, CK-MB r2=0.9) between POCT and Core Lab and a significant decrease of the turn around time (TAT): difference of medians=−54 min, 95% CI from −48 to −60 min. Conclusions: Our data confirmed that the accurate utilization of POCT in the ED assumes an effective triage of patient with chest pain and the improvement of preanalytical phase out of the laboratory (delivery of specimens) and within the laboratory reception, centrifugation. However, efficiency must be linked to methodological and quality control of the Core Lab, mainly through connectivity.

Onset of action, duration and maximum efficacy of different botulinum toxin type A (BoNT/A) preparations have been compared mainly in in vitro studies. This single-center open study compared onset of action of the two BoNT/A preparations onabotulinumtoxinA (complex size 900 kDa) and incobotulinumtoxinA (free of complexing proteins, 150 kDa) in patients with spasticity after cerebral stroke over a 15-day treatment period. Outcome measures were changes in muscle tone, increase in passive extension of the elbow, changes in limb functionality, and variation of the amplitude of the compound muscle action potential (cMAP) determined by electroneurography. A total of 108 patients (mean age 64.8 ± 11.3 years) were included in the study, 54 in each treatment arm. Muscle tone, elbow motion range, and limb function significantly improved in both groups from baseline to day 15 after BoNT/A injection (p

Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib. These identified mRNA were validated in 78 frozen HCC samples and in 26 ex-vivo HCC tissues treated in culture with galunisertib. Respective protein levels in patients blood were measured by enzyme-linked immunosorbent assay. SKIL, PMEPA1 ANGPTL4, SNAI1, Il11 and c4orf26 were strongly upregulated by TGF-β1 and downregulated by galunisertib in different HCC cell lines. In the 78 HCC samples, only SKIL and PMEPA1 (Pβ1. In ex-vivo samples, SKIL and PMEPA1 were strongly downregulated (PPβ1. SKIL and PMEPA1 mRNA expression in tumor tissues was significantly increased compared with controls and not correlated with protein levels in the blood of paired HCC patients. SKIL and PMEPA1 mRNA levels were positively correlated with TGF-β1 mRNA concentrations in HCC tissues and strongly downregulated by galunisertib. The target genes identified here may serve as biomarkers for the stratification of HCC patients undergoing treatment with galunisertib.

Background: Tremolite is one of the six recognized types of asbestos, whose toxicity and carcinogenity is welldocumented. Resident population in the area of Lagonegro (Basilicata, Italy) has been shown to be exposed to enviromental tremolite pollution, deriving from superficial rocks and asbestos caves. A branch of the ongoing health surveillance program for residents is evaluating the prevalence of pulmonary functional abnormalities. Methods: The study group was composed by 655 long-term residents in the tremolite-exposed area of Lagonegro (age 49.35 ± 16.68, current smokers 109, ex-smokers 126) . The control group was composed by 653 individuals living in areas not tremolite-exposed (age 54.45 ± 17.16, current smokers 128, ex-smokers 137). All the participants to the study performed a lung function test. Results: Prevalence of obstructive and restrictive diseases did not show significant differences between the two groups. Tremolite-exposed group showed a higher prevalence of small-airways disease compared to the nonexposed group (p

Epidemiological studies suggest a possible association between BMI, diagnosis and clinical-pathological breast cancer characteristics but biological bases for this relationship still remain to be ascertained. Several biological mechanisms play a role in the genesis and progression of breast cancer. This study aimed to investigate relationships between BMI and breast cancer diagnosis/progression in a Southern Italian population and to try to interpret results according to the serum proteomic profile of healthy and breast cancer patients. BMI, presence or absence of breast cancer and its clinical-pathological characteristics were analyzed in a series of 300 breast cancer women and compared with those of 300 healthy women prospectively. To investigate whether obesity is associated with alterations in serum protein profile, SELDI-ToF approach was applied. Alcohol consumption (22.7% vs 11.3%; p = 30 respect to normal weight: OR = 2.49, 95% CI 1.25–4.99, p = 0.0098) and a higher probability of having positive axillary lymph node (OR = 3.67, CI 95% 2.16–6.23, p

To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively.Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes.BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months.Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.