Genome-wide association studies for iris pigmentation and heterochromia patterns in Large White pigs.

Eye colour genetics have been extensively studied in humans since the rediscovery of Mendel's laws. This trait was first interpreted using simplistic genetic models but soon it was realised that it is more complex. In this study, we analysed eye colour variability in a Large White pig population (n = 897) and report the results of GWASs based on several comparisons including pigs having four main eye colour categories (three with both pigmented eyes of different brown grades: pale, 17.9%; medium, 14.8%; and dark, 54.3%; another one with both eyes completely depigmented, 3.8%) and heterochromia patterns (heterochromia iridis - depigmented iris sectors in pigmented irises, 3.2%; heterochromia iridum - one whole eye iris of depigmented phenotype and the other eye with the iris completely pigmented, 5.9%). Pigs were genotyped with the Illumina PorcineSNP60 BeadChip and GEMMA was used for the association analyses. The results indicated that SLC45A2 (on chromosome 16, SSC16), EDNRB (SSC11) and KITLG (SSC5) affect the different grades of brown pigmentation of the eyes, the bilateral eye depigmentation defect and the heterochromia iridis defect recorded in this white pig population respectively. These genes are involved in several mechanisms affecting pigmentation. Significant associations for the eye depigmented patterns were also identified for SNPs on two SSC4 regions (including two candidate genes: NOTCH2 and PREX2) and on SSC6, SSC8 and SSC14 (including COL17A1 as candidate gene). This study provided useful information to understand eye pigmentation mechanisms, further valuing the pig as animal model to study complex phenotypes in humans.

Gene co-expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency.

BACKGROUND: Selection for feed efficiency is crucial for overall profitability and sustainability in dairy cattle production. Key regulator genes and genetic markers derived from co-expression networks underlying feed efficiency could be included in the genomic selection of the best cows. The present study identified co-expression networks associated with high and low feed efficiency and their regulator genes in Danish Holstein and Jersey cows. RNA-sequencing data from Holstein and Jersey cows with high and low residual feed intake (RFI) and treated with two diets (low and high concentrate) were used. Approximately 26 million and 25 million pair reads were mapped to bovine reference genome for Jersey and Holstein breed, respectively. Subsequently, the gene count expressions data were analysed using a Weighted Gene Co-expression Network Analysis (WGCNA) approach. Functional enrichment analysis from Ingenuity® Pathway Analysis (IPA®), ClueGO application and STRING of these modules was performed to identify relevant biological pathways and regulatory genes. RESULTS: WGCNA identified two groups of co-expressed genes (modules) significantly associated with RFI and one module significantly associated with diet. In Holstein cows, the salmon module with module trait relationship (MTR) = 0.7 and the top upstream regulators ATP7B were involved in cholesterol biosynthesis, steroid biosynthesis, lipid biosynthesis and fatty acid metabolism. The magenta module has been significantly associated (MTR = 0.51) with the treatment diet involved in the triglyceride homeostasis. In Jersey cows, the lightsteelblue1 (MTR = - 0.57) module controlled by IFNG and IL10RA was involved in the positive regulation of interferon-gamma production, lymphocyte differentiation, natural killer cell-mediated cytotoxicity and primary immunodeficiency. CONCLUSION: The present study provides new information on the biological functions in liver that are potentially involved in controlling feed efficiency. The hub genes and upstream regulators (ATP7b, IFNG and IL10RA) involved in these functions are potential candidate genes for the development of new biomarkers. However, the hub genes, upstream regulators and pathways involved in the co-expressed networks were different in both breeds. Hence, additional studies are required to investigate and confirm these findings prior to their use as candidate genes.

Transcriptomics-genomics data integration and expression quantitative trait loci analyses in oocyte donors and embryo recipients for improving invitro production of dairy cattle embryos.

In this paper we first provide a brief review of main results from our previously published studies on genome-wide gene expression (transcriptomics) in donor and recipient cattle used in invitro production (IVP) of embryos and embryo transfer (ET). Then, we present novel results from applying integrative systems genomics and biological analyses where transcriptomics data are combined with genomic data in both donor and recipient cattle to map expression quantitative trait loci (eQTLs). The eQTLs are genetic markers that can regulate or control the expression of genes in the entire genome, via complex molecular mechanisms, and thus can act as a powerful tool for genomic and gene-assisted selection. We identified significant eQTLs potentially controlling the expression of 13 candidate genes for donor cow quality (IVP parameters; e.g. cyclin B1 (CCNB1), outer dense fiber of sperm tails 2 like (ODF2L)) and 19 candidate genes for recipient cows quality (endometrial receptivity; e.g. ER membrane protein complex subunit 9 (EMC9), mannosidase beta (MANBA), peptidase inhibitor 16 (PI16)). Annotation and colocation of detected eQTLs show that some of the eQTLs are in the same genomic regions previously reported as QTLs for reproduction-related traits. However, eQTLs and the candidate genes identified should be further validated in larger populations before implementation as genetic markers or used in genomic selection for improving IVP and ET performance.

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle.

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.

Genome-wide association study for the level of serum electrolytes in Italian Large White pigs.

Calcium, magnesium and phosphorus are essential electrolytes involved in a large number of biological processes. Imbalance of these minerals in blood may indicate clinically relevant conditions and are important in inferring acute or chronic pathologies in humans and animals. In this work, we carried out a genome-wide association study (GWAS) for the level of these three electrolytes in the serum of 843 performance-tested Italian Large White pigs. All pigs were genotyped with the Illumina PorcineSNP60 BeadChip, and GWAS was carried out using genome-wide efficient mixed-model association. For the level of Ca(2+) , eight single nucleotide polymorphisms (SNPs) were significant, considering a false discovery rate (FDR) < 0.05, and another eight were above the moderate association threshold (Pnominal value  < 5.00E-05). These SNPs are distributed in four porcine chromosomes (SSC): SSC8, SSC11, SSC12 and SSC13. In particular, a few putative different signals of association detected on SSC13 and one on SSC12 were in genes or close to genes involved in calcium metabolism (P2RY1, RAP2B, SLC9A9, C3orf58, TSC22D2, PLCH1 and CACNB1). Only one SNP (on SSC7) and six SNPs (on SSC2 and SSC7) showed moderate association with the level of magnesium and phosphorus respectively. The association signals for these two latter minerals might identify genes not known thus far for playing a role in their biological functions and regulations. In conclusion, our GWAS contributed to increased knowledge on the role that calcium, magnesium and phosphorus may play in the genetically determined physiological mechanisms affecting the natural variability of mineral levels in mammalian blood.

Budget impact analysis of universal rotavirus vaccination in the Local Health Unit 11 Empoli, Tuscany, Italy.

BACKGROUND: Rotavirus (RV) infection is the first cause of acute viral gastroenteritis in children under five years of age all over the world; it mainly affects children between six and 24 months of age and can cause serious acute diarrhoea and dehydration. The aim of this study is to perform the budget impact analysis of universal rotavirus vaccination in the Local Health Unit (LHU) 11 Empoli, Tuscany, Italy. METHODS: An ad hoc mathematical simulation model was developed to evaluate the budget impact analysis of 5-years universal rotavirus vaccination. Particularly, incidence of rotavirus gastroenteritis (RVGE), hospitalizations, nosocomial diarrhoea, medical consultations, prescriptions and accesses to emergency department were taken into account in the analysis. The direct medical costs due to RV diarrhoea and the costs of vaccination campaign were considered as the main outcome measures in the study. RESULTS: The adoption of universal rotavirus vaccination campaign for five years in the LHU 11 Empoli would result in relevant savings due to the health cares avoided. These savings would overlapped the costs of vaccination yet from the second year after the introduction of vaccination. The saving for the Health Service would be 1.5 million Euro after five years of campaign. CONCLUSIONS: Universal vaccination against rotavirus results clinically and economically favourable for both the Health Service and the Society perspectives.

Robotic transabdominal retromuscular rectus diastasis (r-TARRD) repair: a new approach.

PURPOSE: The aim of this study is to present our innovative robotic approach for the treatment of rectus diastasis with concurrent primary or incisional ventral hernias. METHODS: We performed 45 r-TARRD repairs for symptomatic rectus diastasis with concomitant associated ventral/incisional umbilical and/or epigastric hernias between January 2019 and January 2020. Data on patient demographics, type of hernia, operative time, complications, recurrence rate, and hospital stay were retrospectively analyzed. Follow-up was scheduled at 1, 6 months, and 1 year after surgery. RESULTS: 45 patients (13 M, 32 F) underwent r-TARRD repair. Mean age was 54.8 years (range 31-68) and mean BMI was 26.74 kg/m2 (range 21.1-31). Mean ASA was 2.2 (range 1-3). In all patients we used a polypropylene mesh 25 × 15 cm, properly shaped. Mean operative time was 192 min (range 115-260). Mean hospital stay 4.2 days (range 2-7). No conversion to laparoscopy or open surgery and no major complications occurred. At 1-month follow-up one mesh infection (2.22%) was observed and it was treated conservatively. Four recurrences (8.88%) were reported at 1-year follow-up. CONCLUSIONS: Robot-assisted TARRD repair is conceived as a novel alternative minimally invasive procedure for RD with concurrent midline defects ensuring a primary fascial defect closure and mesh implantation in a sublay position with a wide overlap. It is important to better evaluate the suture that should be used to perform the repair, and multicenter studies with standardization of patient's demographics, RD characteristics, and long-term follow-up outcomes are mandatory to assess the effectiveness and durability of r-TARDD repair.

Adherence to a guided walking program with amelioration of cognitive functions in subjects with schizophrenia even during COVID-19 pandemic.

BACKGROUND: Aim of the study was to enrol a group of individuals with schizophrenia in a long-term moderate-intensity physical activity program and to evaluate its effects on their cognitive functions and cardiovascular risk factors. An additional aim of the study was the comparison of the adherence to the physical activity program before and during the COVID-19 pandemic. METHODS: Forty sedentary patients diagnosed with schizophrenia (mean age 46.4 ± 9.6) followed by the Public Mental Health Department of Ferrara were included in the study. 28 of them followed a 1-year walking program consisting of two guided walking sessions/week, while 12 maintained their sedentary lifestyle and followed the usual Cognitive Rehabilitation program. To the participants following the walking program VO2 peak and walking speed were assessed at baseline and at the end of the program. All participants were evaluated on blood pressure and anthropometric variable. Cognitive functions were assessed with the Screen for Cognitive Impairment in Psychiatry (SCIP) and with the Frontal Assessment Battery (FAB) questionnaires. RESULTS: The 20 participants completing the walking program displayed significant improvements in cognitive functions (dppc2 0.35 for SCIP and 0.26 for FAB), with a positive correlation between SCIP score and the number of sessions attended (R = 0.86, p < 0.001), evident in the patients attending to at least 75 of the 100 walking sessions. Walking speed and VO2peak increased significantly and a decrease of body weight, BMI, systolic and diastolic blood pressure was also observed. The adherence to the walking program registered during Covid-19 period did not differ from that observed before the pandemic. The 12 CG (Control Group) patients maintaining the sedentary lifestyle did not display improvements of cognitive functions. CONCLUSIONS: The main finding of this study is the improvement of cognitive functions which is significantly related to the number of walking sessions attended by participants with schizophrenia. The walking program, guided by exercise specialists, proved to be an enjoyable activity for people with mental disorder feasible even during the COVID-19 pandemic. Trial registration Retrospectively registered on ISRCTN as non-randomized trial (n. ISRCTN14763786).

Robotic-assisted single site (RASS) TAPP: an advantageous choice? : Outcomes of single site robotic groin hernia repair.

PURPOSE: Laparoscopic transabdominal preperitoneal (TAPP) is a valid option for bilateral primary groin hernia and recurrent cases. Robotic approach for inguinal hernia is still debated. The aim of this study is to investigate the potential role of robotic-assisted single site-TAPP (RASS-TAPP) reporting our experience. METHODS: We performed 44 RASS TAPP in 32 patients from February 2016 to July 2018. Data on patient demographics, type of hernia, operative time, complications, recurrence rate and hospital stay were retrospectively analyzed. Follow-up was scheduled at 1 week, 4 months and 1 year after surgery. RESULTS: Forty-two hernias were treated in 32 patients (27 M). Mean age was 48.6 years (range 20-67), mean BMI was 26.49 kg/m2 (range 16-34.9). Mean operative time was 54.8 min (range 28-150). In two cases (6%) a conversion to laparoscopy was necessary. At 1 week, two scrotal hematomas and four seromas were observed and treated conservatively. At 4 months follow-up, one patient (3.1%) complained temporary pain. No patient had inguinal recurrence or incisional umbilical hernia and chronic pain at 1-year follow-up. CONCLUSION: RASS TAPP is feasible and safe with a high patient satisfaction. However, the surgeon experiences a technical discomfort due to the conflict of the instrumentation which influences negatively the choice of this approach, despite the better vision and augmented dexterity provided by the robot.

Improved percent-predicted peak VO2 is associated with lower risk of hospitalization in patients with coronary heart disease. Analysis from the FRIEND registry.

BACKGROUND: Normal standards for peak oxygen consumption (VO2peak) are controversial because they tend to be population and protocol specific. This study was undertaken to examine the association between percentage of age-predicted VO2peak and all-cause hospital readmission in cardiac outpatients who were referred to an exercise-based secondary prevention program. METHODS: Hospital readmission was assessed in 1283 male patients with coronary heart disease (CHD) three years after enrolment, and related to the age-predicted VO2peak derived from the Fitness Registry and the Importance of Exercise: A National Data Base equation (FRIEND%PRED). VO2peak was estimated using a moderate perceptually regulated 1-km treadmill-walking test. Readmission was also assessed during the fourth-to-sixth years as function of improvement in FRIEND%PRED in 845 patients who were re-evaluated 3 years after baseline. RESULTS: During the 3-years after baseline, readmission rate was lower across increasing tertiles of FRIEND%PRED. Compared to the lowest tertile, the adjusted hazard ratios (HRs) for the second and third tertile were 0.98 (95% CI 0.76-1.27, p = 0.90) and 0.71 (0.53-0.95, p = 0.002). The rate of readmission from the fourth-to-sixth years after baseline was lower across tertiles of improved FRIEND%PRED, with adjusted HRs 0.78 (0.60-1.03, p = 0.08) and 0.58 (0.42-0.75, p < 0.0001) for the intermediate and high tertiles vs the lowest tertile. After adjustment for confounders, every 1 unit % increase in FRIEND%PRED was associated with a 3% reduction in risk of readmission (HR 0.97, 0.95-0.98, p < 0.0001). CONCLUSIONS: Age-predicted VO2peak estimated by a moderate treadmill-walk predicts hospital readmission in outpatients with CHD undergoing secondary prevention.

Our Timing to Remove Peritoneal Catheter Dialysis After Kidney Transplant.

BACKGROUND: Patients on peritoneal dialysis treatment represent 15% of the global dialysis population. The major complication of peritoneal dialysis is catheter and peritoneal infection. Peritoneal dialysis patients who receive kidney transplants are at increased risk of infection because of immunosuppressive therapy. AIM: The purpose of this study is to show our ideal timing to remove peritoneal catheter after kidney transplant, which gives adequate security on renal function recovery and reduction of septic risk. METHOD OF STUDY: We analyzed the outcomes of 65 patients on peritoneal dialysis who underwent kidney transplant between 2000 and 2016. RESULTS: In 61 cases there was an immediate graft functional recovery. In 4 cases there was a delayed graft function (DGF), and we performed a hemodialysis with temporary placement of a venous catheter. In all patients we removed peritoneal dialysis catheter 30 to 45 days after transplant. There has been 1 case of catheter infection, which was treated with antibiotic therapy. DISCUSSION: Our average time to remove the peritoneal dialysis catheter was shorter than times in previous studies, between the 30th and 45th postoperative day. In the 4 cases in which there has been a DGF, we performed hemodialysis treatment to avoid, in the immediate postoperative period, direct insults to the peritoneum by local dialysis procedures. CONCLUSION: Our experience show that the 30th to 45th postoperative day is a good time frame, better yet a good watershed between the safe removal of peritoneal catheter when patients have a stabilized renal function and the possibility of leaving it in situ, to resume peritoneal dialysis in case of persistent DGF.

Genomic study and Medical Subject Headings enrichment analysis of early pregnancy rate and antral follicle numbers in Nelore heifers.

Zebu animals () are known to take longer to reach puberty compared with taurine animals (), limiting the supply of animals for harvest or breeding and impacting profitability. Genomic information can be a helpful tool to better understand complex traits and improve genetic gains. In this study, we performed a genomewide association study (GWAS) to identify genetic variants associated with reproductive traits in Nelore beef cattle. Heifer pregnancy (HP) was recorded for 1,267 genotyped animals distributed in 12 contemporary groups (CG) with an average pregnancy rate of 0.35 (±0.01). Disregarding one of these CG, the number of antral follicles (NF) was also collected for 937 of these animals, with an average of 11.53 (±4.43). The animals were organized in CG: 12 and 11 for HP and NF, respectively. Genes in linkage disequilibrium (LD) with the associated variants can be considered in a functional enrichment analysis to identify biological mechanisms involved in fertility. Medical Subject Headings (MeSH) were detected using the MESHR package, allowing the extraction of broad meanings from the gene lists provided by the GWAS. The estimated heritability for HP was 0.28 ± 0.07 and for NF was 0.49 ± 0.09, with the genomic correlation being -0.21 ± 0.29. The average LD between adjacent markers was 0.23 ± 0.01, and GWAS identified genomic windows that accounted for >1% of total genetic variance on chromosomes 5, 14, and 18 for HP and on chromosomes 2, 8, 11, 14, 15, 16, and 22 for NF. The MeSH enrichment analyses revealed significant ( < 0.05) terms associated with HP-"Munc18 Proteins," "Fucose," and "Hemoglobins"-and with NF-"Cathepsin B," "Receptors, Neuropeptide," and "Palmitic Acid." This is the first study in Nelore cattle introducing the concept of MeSH analysis. The genomic analyses contributed to a better understanding of the genetic control of the reproductive traits HP and NF and provide new selection strategies to improve beef production.

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds.

In pigs, many production traits are known to vary among breeds or lines. These traits can be considered end phenotypes or external traits as they are the final results of complex biological interactions and processes whose fine biological mechanisms are still largely unknown. This study was designed to compare plasma and serum metabolomic profiles between animals of two heavy pig breeds (12 Italian Large White and 12 Italian Duroc), testing indirectly the hypothesis that different genetic backgrounds might be the determining factors of differences observed on the level of metabolites in the analyzed biofluids between breeds. We used a targeted metabolomic approach based on mass spectrometric detection of about 180 metabolites and applied a statistical validation pipeline to identify differences in the metabolomic profiles of the two heavy pig breeds. Blood samples were collected after jugulation at the slaughterhouse and prepared for metabolomics analysis that was carried out using the Biocrates AbsoluteIDQ p180 Kit, covering five different biochemical classes: glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines. A statistical pipeline that included the selection of the most relevant metabolites differentiating the two breeds by sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was coupled with a stability test and significance test determined with leave one out and permutation procedures. sPLS-DA plots clearly separated the pigs of the two investigated breeds. A few metabolites (a total of five metabolites considering the two biofluids) involved in key metabolic pathways largely contributed to these differences between breeds. In particular, a higher level of the sphingomyelins SM (OH) C14:1 (both in plasma and serum), SM (OH) C16:1 (in serum) and SM C16:0 (in serum) were observed in Italian Duroc than in Italian Large White pigs and the inverse was for the biogenic amine kynurenine (in plasma). The level of another biogenic amine (acetylornithine) was higher in Italian Large White than in Italian Duroc pigs in both analysed biofluids. These results provided biomarkers that could be important to understand the biological differences between these two heavy pig breeds. In particular, according to the functional role played by sphingomyelins in obesity-induced inflammatory responses, it could be possible to speculate that a higher level of sphingomyelins in Italian Duroc might be related to the higher interrmuscular fat deposition of this breed compared with the Italian Large White. Additional studies will be needed to evaluate the relevance of these biomarkers for practical applications in pig breeding and nutrition.

[Colorectal carcinoma in the young. Prognostic factors]. / Il carcinoma colo-rettale nel giovane. Fattori prognostici.

Colorectal carcinoma is the third most frequently diagnosed malignant neoplasm. Usually patients affected by this neoplasia belong to VI decade of life. However approximately 2-8% of tumors arise in patients with age under 40 years. Aim of the study was to analyse the results of surgical treatment of colorectal cancer in patients aged under forty. From January 1987 to December 2002, 46 patients under forty years with colorectal cancer underwent surgical procedure. No perioperative mortality was registered, and complications were evidenced in nine patients (20%). Actuarial five years survival was 33%, and overall mean survival was 53 months. Univariate and multivariate analyses identified as prognostic factors the tumor grade, Dukes' stage, nodal status, and length of symptoms.

Deconstructing the pig sex metabolome: Targeted metabolomics in heavy pigs revealed sexual dimorphisms in plasma biomarkers and metabolic pathways.

Metabolomics has opened new possibilities to investigate metabolic differences among animals. In this study, we applied a targeted metabolomic approach to deconstruct the pig sex metabolome as defined by castrated males and entire gilts. Plasma from 545 performance-tested Italian Large White pigs (172 castrated males and 373 females) sampled at about 160 kg live weight were analyzed for 186 metabolites using the Biocrates AbsoluteIDQ p180 Kit. After filtering, 132 metabolites (20 AA, 11 biogenic amines, 1 hexose, 13 acylcarnitines, 11 sphingomyelins, 67 phosphatidylcholines, and 9 lysophosphatidylcholines) were retained for further analyses. The multivariate approach of the sparse partial least squares discriminant analysis was applied, together with a specifically designed statistical pipeline, that included a permutation test and a 10 cross-fold validation procedure that produced stability and effect size statistics for each metabolite. Using this approach, we identified 85 biomarkers (with metabolites from all analyzed chemical families) that contributed to the differences between the 2 groups of pigs ( < 0.05 at the stability statistic test). All acylcarnitines and almost all biogenic amines were higher in castrated males than in gilts. Metabolites involved in tryptophan catabolism had the largest differences (i.e., delta = 20% for serotonin) between castrated males (higher) and gilts (lower). The level of several AA (Ala, Arg, Gly, His, Lys, Ser, Thr, and Trp) was higher in gilts (delta was from approximately 1.0 to approximately 4.8%) whereas products of AA catabolism (taurine, 2-aminoadipic acid, and methionine sulfoxide) were higher in castrated males (delta was approximately 5.0-6.0%), suggesting a metabolic shift in castrated males toward energy storage and lipid production. Similar general patterns were observed for most sphingomyelins, phosphatidylcholines, and lysophosphatidylcholines. Metabolomic pathway analysis and pathway enrichment identified several differences between the 2 sexes. This metabolomic overview opened new clues on the biochemical mechanisms underlying sexual dimorphism that, on one hand, might explain differences in terms of economic traits between castrated male pigs and entire gilts and, on the other hand, could strengthen the pig as a model to define metabolic mechanisms related to fat deposition.

Renal homotransplantation with venous outflow or infusion of antigen into the portal vein of dogs or pigs. Transplantation at portal site.

Kidneys were transplanted in mongrel dogs so that renal venous drainage was into the portal system of the hosts. Thirty-one recipients were not treated, 11 were given one dose of 3 mg of azathioprine per kg, and 11 were given 2 mg of azathioprine per day. Survival was not statistically increased compared with that in three comparable series in which renal venous drainage was into the vena cava, nor were the histopathological findings favorably altered in the "portal" kidneys. The injection of semisoluble antigen into the portal vein at the same time as renal transplantation at the caval site, had an effect no different from that if the antigen were given systemically during caval site transplantation. The conclusion that drainage of grafts into the portal vein was not beneficial was reached in 20 pigs evenly divided between the portal and vena caval sites, and in 12 pairs of dog to pig or pig to dog xenografts. Thus, none of these experiments has identified an advantage of antigen delivery into the portal as opposed to the systemic venous system.

The role of serum and gastric juice levels of carcinoembryonic antigen, CA19.9 and CA72.4 in patients with gastric cancer.

PURPOSE: The aim of the present study was to investigate carcinoembryonic antigen (CEA), CA19.9, and CA72.4 in the serum and gastric juice of patients with gastric cancer. METHODS: Serum and gastric juice tumor markers CEA, CA19.9, and CA72.4 were measured in 59 patients who had gastric adenocarcinomas and were undergoing curative gastrectomy. The same markers were measured in 47 patients with benign gastric disorders and in 40 healthy subjects. The correlation between the serum and gastric juice levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed both by univariate and multivariate analysis. RESULTS: The positivity rates of serum CEA, CA19.9, and CA72.4 were 57.6%, 38.9%, and 18.6% respectively. The positivity rates of gastric juice CEA, CA19.9, and CA72.4 were 62.7%, 30.5%, and 23.7% respectively. The combination of serum and gastric juice markers gave a positivity of 81.3%. There was no correlation between serum and gastric juice level of each tumor marker. Positivity of gastric juice markers did not correlate with prognosis. A significant difference in prognosis was observed between patients positive and negative for serum CEA and CA19.9. Multivariate analysis also revealed that serum CEA and CA19.9 levels were independent prognostic factors. CONCLUSIONS: Levels of both serum and gastric juice tumor markers continue to have only limited diagnostic usefulness in gastric cancer patients. CEA and CA19.9 in the preoperative sera are good prognostic factors, whereas the presence of tumor markers in the gastric juice does not play any prognostic role.

The need for antibiotic prophylaxis in elective laparoscopic cholecystectomy: a prospective randomized study.

HYPOTHESIS: The need for antibiotic treatment when performing elective laparoscopic cholecystectomy may not be as important as it is thought. This study assesses the real efficacy of antibiotic prophylaxis in elective laparoscopic cholecystectomy with respect to the postoperative infection rate. DESIGN: A prospective randomized study on the routine use of antibiotic prophylaxis in laparoscopic cholecystectomy. SETTING: University teaching hospital, La Sapienza, Italy. PATIENTS: Eighty-four patients randomly placed into 2 groups (A [n = 44] and B [n = 40]) immediately before undergoing laparoscopic cholecystectomy. METHODS: Before anesthesia was administered, group A received intravenously 2 g of cefotaxime sodium diluted in 100 mL of isotonic sodium chloride solution; group B, 10 mL of isotonic sodium chloride solution in 100 mL of saline. A gallbladder bile sample for culture was withdrawn intraoperatively from all patients. In both groups, age, sex, weight, duration of surgery, presence of diabetes, American Society of Anesthesiologists patient classification score, preoperative autologous blood donation, antibiotic administration, intraoperative gallbladder rupture, findings from bile culture positive for bacteria, episodes of colic within 30 days before surgery, length of postoperative hospital stay, and number of septic complications were recorded. All data were correlated by univariate and multivariate analyses with the onset of septic phenomena. RESULTS: In group A, 3 cases of wound infection, 1 case of subhepatic abscess from bile leakage, and 1 case of urinary tract infection were observed; group B, 4 cases of wound infection, 1 case of bronchopneumonia, and 2 cases of urinary tract infection. Comparison of data showed no statistically significant difference between the groups. Findings from bile examination in patients with sepsis complications were positive in 5 patients in group A and in 6 in group B (P = .91). Multivariate analysis showed diabetes mellitus and colic episodes within 30 days before surgery as independent factors significantly associated to the onset of infectious complications. CONCLUSIONS: In elective laparoscopic cholecystectomy, antibiotic treatment did not seem to affect the incidence and severity of infections or the degree of bile contamination.

Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences.

HYPOTHESIS: Total mesorectal excision lowers the rate of pelvic recurrence and positively affects the survival after surgical treatment of rectal cancer. DESIGN: Case series. SETTING: Tertiary care university hospital. PATIENTS: Fifty-three consecutive patients were admitted with curative intent to surgery at the First Department of Surgery of the University of Rome "La Sapienza," Rome, Italy, with diagnoses of rectal carcinoma. The mean follow-up was 68.9 months; follow-up was complete for all patients who entered the trial. INTERVENTIONS: Low anterior resection and total mesorectal excision were performed in all cases, regardless of the location of the rectal cancer. A straight mechanical colorectal anastomosis was performed on a rectal stump, never exceeding 5 cm. No kind of adjuvant therapy was given. Mesorectum and open rectum were studied by serial transverse section at 5-mm intervals. A search for depth of penetration and distal intramural extension of the tumor was made. Lymph nodes were detected by clearing method, and nodal metastases (NM) and nonnodal metastases (NNM) were recorded as situated proximally, distally, or at the level of the tumor. RESULTS: There was no postoperative mortality. Clinical and radiologic leaks occurred in 2 and 4 patients, respectively. Mean disease-free survival was 65.9 months. Pelvic recurrence occurred in 5 patients (9%). Overall 5-year survival rate was 75%. Involvement of mesorectum by NM and NNM was detected in 27 and 24 cases, respectively. Both NM and NNM were found to be distal in 33% and 40% of cases, respectively. CONCLUSIONS: Microscopic spread to the distal mesorectum may exceed the intramural spread of rectal cancer. Failure to perform total mesorectal excision leaves a potentially residual disease in the distal mesorectum, thus predisposing the patient to pelvic recurrence.