Total orthotopic small bowel transplantation in swine under FK 506

Previous experimental studies in rodents and in dogs have established the efficacy of FK 506 in controlling the immunologic events following small bowel or multivisceral transplantation.1–5 To complete the assessment of FK 506 in experimental small bowel transplantation, we present here our experience with the frequently used swine model

Mediterranean diet and outcomes of assisted reproduction: an Italian cohort study

Background: Detrimental lifestyle habits have been indicated as potential causes of reduced fertility. Recently studies have suggested an association between healthy diets and increased live birth rates after assisted reproduction techniques. However, the issue remains under debate, and evidence is still accumulating. Objective: The objective of the study was to study the relationship between a Mediterranean diet and outcomes of assisted reproduction techniques in subfertile couples in an Italian population. Study Design: This was a prospective cohort study, conducted in an Italian fertility clinic. Couples undergoing in vitro fertilization were interviewed on the day of oocyte retrieval to obtain information on personal and health history, lifestyle habits, and diet. Adherence to a Mediterranean diet was evaluated using a Mediterranean diet score. Relative risks and 95% confidence intervals for embryo transfer, clinical pregnancy, and live birth were calculated. Potential confounders were included in the equation model. Results: Among 474 women (mean age, 36.6 years, range, 27\u201345), 414 (87.3%) performed embryo transfer, 150 (31.6%) had clinical pregnancies, and 117 (24.7%) had live births. In a model including the potential confounders (age, leisure physical activity, body mass index, smoking, daily calorie intake, and previous failed in vitro fertilization cycles), findings showed that the Mediterranean diet score was not significantly associated with in vitro fertilization outcomes. Adjusted analyses were performed in strata of age, previous assisted reproduction technique cycles, and reasons for infertility, with consistent findings. The only exception was observed in women >35 years old with an intermediate Mediterranean diet score, who showed a lower risk of not achieving clinical pregnancy (adjusted relative risk, 0.84, 95% confidence interval, 0.71\u20131.00, P = .049). Conclusion: No clear association was observed between adherence to a Mediterranean diet and successful in vitro fertilization

The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols

The advent of random start protocols to shorten the time needed to store oocytes in women with malignancies has represented an important improvement in the field of fertility preservation. However, Randomized Controlled Trials are difficult to implement in this area and available evidence that supports this approach remains modest. To shed more light on this issue, we compared the follicular development between the ovary carrying the dominant follicle or the corpus luteum and the contralateral resting ovary in 90 women who underwent random start controlled ovarian stimulation (COS). In fact, ovarian response did not differ between the two ovaries. Subgroup analyses according to the phase of the cycle at the initiation of COS, the type of malignancy, the use of letrozole and the magnitude of the ovarian response did not allow to identify any condition showing a difference in the follicular response between the active and the resting ovaries. In conclusion, follicular growth does not seem to be perturbed by the presence of a dominant follicle or a corpus luteum

Dietary carbohydrate intake, dietary glycemic load and outcomes of in vitro fertilization : Findings from an observational italian cohort study

In recent decades, increasing attention has been paid to the influence of diet on reproductive health. Carbohydrates in diet affect glucose metabolism and multiple evidences showed the key role of insulin sensitivity in regulating female fertility. We designed a prospective cohort study to investigate the relation between dietary carbohydrate intake, glycemic load (GL) and the outcomes of assisted reproduction. A population of 494 female partners of couples referring to an Italian Fertility Center and eligible for in vitro fertilization (IVF) were enrolled in the study. On the day of the oocyte retrieval, information on their diet was obtained using a validated food frequency questionnaire (FFQ). We calculated the relative risk and 95% confidence interval of embryo transfer, clinical pregnancy and live birth according to the following dietary exposures: GL, glycemic index (GI) as well as the daily carbohydrate and fiber intake. A multiple regression model was used to account for the confounders. After adjusting for age, college degree, body mass index (BMI), leisure physical activity and previous assisted reproduction techniques (ART) cycles, no significant association was observed between the considered dietary exposures and the IVF outcomes. The roles of GL, carbohydrate intake and GI were assessed in strata of the cause of infertility and body mass index and no relation emerged in this further analysis. We found no clear association between the dietary carbohydrate quantity and quality and IVF outcomes in a cohort of infertile Italian women

VGF peptide profiles in Type 2 diabetic patients' plasma and in obese mice

To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment

Reply: On the Reporting of Odds Ratios and Risk Ratios, Nutrients 2018, 10, 10

In response to the letter of Pace and Multani, in general, we cannot disagree with their considerations about the use of odds ratios, risk ratios, and rate ratios. [...]

Alcohol intake and semen variables: cross-sectional analysis of a prospective cohort study of men referring to an Italian Fertility Clinic

BACKGROUND: The association between alcohol intake and male reproductive function is still controversial. In the frame of a prospective cohort study, designed to investigate the relation between life style and fertility, we performed a cross-sectional analysis of semen quality. METHODS: Men of subfertile couples, referring to an Italian Infertility Unit and eligible for assisted reproductive techniques (ARTs), were asked about their lifestyle: BMI, smoking, caffeine intake, occupational and leisure physical activity (PA) and alcohol intake in the last year before ART procedure. Semen volume, sperm concentration, total sperm count and sperm motility were determined. Age, risk factors for impaired male fertility, caffeine, smoking, leisure PA, days of abstinence and daily calories intake were accounted for in the analyses. RESULTS: Between September 2014 and December 2016, we enrolled 323 male patients, mean age 39.3 years. Thirty-one (9.6%) were abstainers, 97 (30.0%) drank <1-3, 98 (30.3%) 4-7 and 97 (30.0%) 658 alcohol units per week. As compared to men drinking <1-3 units per week, median semen volume was higher in the 4-7 units/week group (3.0 mL, interquartile range, IQR, 2.0-4.0 vs. 2.4 mL, IQR 1.7-3.5), as well as total sperm count (87.9 mil/mL, IQR 20.2-182.1 vs. 51.5 mil/mL, IQR 15.2-114.7). Association with sperm concentration was also significant, with a U-shaped trend in groups of alcohol intake. After adjusting for potential confounders, these relations were confirmed. Similar patterns were observed in subgroups of leisure PA and risk factors for impaired male fertility, although these estimates often lacked statistical significance, presumably because of low sample size. CONCLUSIONS: Moderate alcohol intake appears positively associated to semen quality in male partners of infertile couples undergoing ART

Maternal and paternal caffeine intake and art outcomes in couples referring to an Italian fertility clinic: A prospective cohort

Caffeine intake, a frequent lifestyle exposure, has a number of biological effects. We designed a cohort study to investigate the relation between lifestyle and assisted reproduction technique (ART) outcomes. From September 2014 to December 2016, 339 subfertile couples referring to an Italian fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, smoking, and usual alcohol and caffeine consumption in the year prior to ART were recorded. The mean age of participants was 36.6 \ub1 3.6 years in women and 39.4 \ub1 5.2 years in men. After oocytes retrieval, 293 (86.4%) underwent implantation, 110 (32.4%) achieved clinical pregnancy, and 82 (24.2%) live birth. Maternal age was the main determinant of ART outcome. In a model including women\u2019s age and college degree, smoking habits, calorie and alcohol intake for both partners, previous ART cycles, and partner\u2019s caffeine intake, we did not observe any association between caffeine intake and ART outcome. Using the first tertile of caffeine intake by women as a reference, the adjusted rate ratio (ARR) for live birth was 1.09 (95% confidence interval (CI) 0.79\u20131.50) in the second and 0.99 (95% CI 0.71\u20131.40) in the third tertiles. In conclusion, a moderate caffeine intake by women and men in the year prior to the ART procedure was not associated with negative ART outcomes

A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation

20siBruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.openopenGrassilli, Emanuela; Pisano, Fabio; Cialdella, Annamaria; Bonomo, Sara; Missaglia, Carola; Cerrito, Maria Grazia; Masiero, Laura; Ianzano, Leonarda; Giordano, Federica; Cicirelli, Vittoria; Narloch, Robert; D'Amato, Filomena; Noli, Barbara; Ferri, Gian Luca; Leone, Biagio; Stanta, Giorgio; Bonin, Serena; Helin, Kristian; Giovannoni, Roberto; Lavitrano, MarialuisaGrassilli, Emanuela; Pisano, Fabio; Cialdella, Annamaria; Bonomo, Sara; Missaglia, Carola; Cerrito, Maria Grazia; Masiero, Laura; Ianzano, Leonarda; Giordano, Federica; Cicirelli, Vittoria; Narloch, Robert; D'Amato, Filomena; Noli, Barbara; Ferri, Gian Luca; Leone, Biagio; Stanta, Giorgio; Bonin, Serena; Helin, Kristian; Giovannoni, Roberto; Lavitrano, Marialuis