Adherence to ESMO guidelines on cancer pain management and their applicability to specialist palliative care centers: An observational, prospective, and multicenter study.

INTRODUCTION: Pain management in late-stage cancer patients is a complex clinical problem. The historical guidelines were from the World Health Organization (WHO). Recently, ESMO produced guidelines consistent with 52 recommendations applicable to the entire period of disease since the pain appears. AIM: To evaluate the appropriateness and applicability of ESMO guidelines (EGL) in advanced cancer patients admitted to palliative care. METHOD: An observational, prospective, multicentric study conducted by specialist palliative care centers on cancer patients in the advanced stage. The 52 recommendations were divided into eight macro areas. The adherence levels were expressed as a percentage for each recommendation and have been broken down as high (>75%), medium (50%-75%), and low (<50%). In the case of not adhering to a recommendation, the comment was "not applicable" (NA) or not evaluable (NE). RESULTS: Four hundred seventy-six patients were enrolled in the study. Thirty-five recommendations were considered NA or NE, especially because their application took too long to achieve clinical results, given the condition of the patients. Some interesting opinions on the choice of drugs emerged. At the end of the study, pain dropped from 5.0 to 2.6, patients' satisfaction increased from 3.3 to 4.6, and quality of life improved from 4.4 to 5.5. CONCLUSIONS: Palliative physicians' adherence to EGL was medium. The main contribution of this study was to evaluate their applicability and clinical results in far-advanced patients assisted by palliative care. The selection of useful recommendations and expert opinions can make a contribution to clinical practice.

Transcriptional profiling of swine mammary gland during the transition from colostrogenesis to lactogenesis using RNA sequencing.

BACKGROUND: Colostrum and milk are essential sources of antibodies and nutrients for the neonate, playing a key role in their survival and growth. Slight abnormalities in the timing of colostrogenesis/lactogenesis potentially threaten piglet survival. To further delineate the genes and transcription regulators implicated in the control of the transition from colostrogenesis to lactogenesis, we applied RNA-seq analysis of swine mammary gland tissue from late-gestation to farrowing. Three 2nd parity sows were used for mammary tissue biopsies on days 14, 10, 6 and 2 before (-) parturition and on day 1 after (+) parturition. A total of 15 mRNA libraries were sequenced on a HiSeq2500 (Illumina Inc.). The Dynamic Impact Approach and the Ingenuity Pathway Analysis were used for pathway analysis and gene network analysis, respectively. RESULTS: A large number of differentially expressed genes were detected very close to parturition (-2d) and at farrowing (+ 1d). The results reflect the extraordinary metabolic changes in the swine mammary gland once it enters into the crucial phases of lactogenesis and underscore a strong transcriptional component in the control of colostrogenesis. There was marked upregulation of genes involved in synthesis of colostrum and main milk components (i.e. proteins, fat, lactose and antimicrobial factors) with a pivotal role of CSN1S2, LALBA, WAP, SAA2, and BTN1A1. The sustained activation of transcription regulators such as SREBP1 and XBP1 suggested they help coordinate these adaptations. CONCLUSIONS: Overall, the precise timing for the transition from colostrogenesis to lactogenesis in swine mammary gland remains uncharacterized. However, our transcriptomic data support the hypothesis that the transition occurs before parturition. This is likely attributable to upregulation of a wide array of genes including those involved in 'Protein and Carbohydrate Metabolism', 'Immune System', 'Lipid Metabolism', 'PPAR signaling pathway' and 'Prolactin signaling pathway' along with the activation of transcription regulators controlling lipid synthesis and endoplasmic reticulum biogenesis and stress response.

Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays.

Bovine milk is important for human nutrition, but its fat content is often criticized as a risk factor in cardiovascular disease. Selective breeding programs could be used to alter the fatty acid (FA) composition of bovine milk to improve the healthiness of dairy products for human consumption. Here, we performed a genome-wide association study (GWAS) on bovine milk to identify genomic regions or specific genes associated with FA profile and to investigate genetic differences between the Italian Simmental (IS) and Italian Holstein (IH) breeds. To achieve this, we first characterized milk samples from 416 IS cows and 436 IH cows for their fat profile by gas chromatography. Subjects were genotyped with single nucleotide polymorphism array and a single-marker regression model for GWAS was performed. Our findings confirm previously reported quantitative trait loci strongly associated with bovine milk fat composition. More specifically, our GWAS results revealed significant signals on chromosomes Bos taurus autosome 19 and 26 for milk FA. Further analysis using a gene-centric approach and pathway meta-analysis identified not only some well-known genes underlying quantitative trait loci for milk FA components, such as FASN, SCD, and DGAT1, but also other significant candidate genes, including some with functional roles in pathways related to "Lipid metabolism." Highlighted genes related to FA profile include ECI2, PCYT2, DCXR, G6PC3, PYCR1, and ALG12 in IS, and CYP17A1, ACO2, PI4K2A, GOT1, GPT, NT5C2, PDE6G, POLR3H, and COX15 in IH. Overall, the breed-specific association outcomes reflect differences in the genetic backgrounds of the IS and IH breeds and their selective breeding histories.

MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

Genome-wide analysis of Italian sheep diversity reveals a strong geographic pattern and cryptic relationships between breeds.

Italy counts several sheep breeds, arisen over centuries as a consequence of ancient and recent genetic and demographic events. To finely reconstruct genetic structure and relationships between Italian sheep, 496 subjects from 19 breeds were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds from the Sheep HapMap dataset was also included in the analyses. Genetic distances (as visualized either in a network or in a multidimensional scaling analysis of identical by state distances) closely reflected geographic proximity between breeds, with a clear north-south gradient, likely because of high levels of past gene flow and admixture all along the peninsula. Sardinian breeds diverged more from other breeds, a probable consequence of the combined effect of ancient sporadic introgression of feral mouflon and long-lasting genetic isolation from continental sheep populations. The study allowed the detection of previously undocumented episodes of recent introgression (Delle Langhe into the endangered Altamurana breed) as well as signatures of known, or claimed, historical introgression (Merino into Sopravissana and Gentile di Puglia; Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese). Arguments that would question, from a genomic point of view, the current breed classification of Bergamasca and Biellese into two separate breeds are presented. Finally, a role for traditional transhumance practices in shaping the genetic makeup of Alpine sheep breeds is proposed. The study represents the first exhaustive analysis of Italian sheep diversity in an European context, and it bridges the gap in the previous HapMap panel between Western Mediterranean and Swiss breeds.

Technical note: Advantages and limitations of authenticating Palmera goat dairy products by pyrosequencing the melanocortin 1 receptor (MC1R) gene.

Inferring the breed of origin of dairy products can be achieved through molecular analysis of genetic markers with a population-specific pattern of segregation. The goal of the current work was to generate such markers in goats by resequencing several pigmentation genes [melanocortin 1 receptor (MC1R), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), tyrosinase (TYR), and tyrosinase-related protein 2 (TYRP2)]. This experiment revealed 10 single nucleotide polymorphisms (SNP), including 5 missense mutations and 1 nonsense mutation. These markers were genotyped in 560 goats from 18 breeds originally from Italy, the Iberian Peninsula, the Canary Islands, and North Africa. Although the majority of SNP segregated at moderate frequencies in all populations (including 2 additional markers that were used as a source of information), we identified a c.764G>A SNP in MC1R that displayed highly divergent allelic frequencies in the Palmera breed compared with the Majorera and Tinerfeña breeds from the Canary Islands. Thus, we optimized a pyrosequencing-based technique that allowed us to estimate, very accurately, the allele frequencies of this marker in complex DNA mixtures from different individuals. Once validated, we applied this method to generating breed-specific DNA profiles that made it possible to detect fraudulent cheeses in which Palmero cheese was manufactured with milk from Majorera goats. One limitation of this approach, however, is that it cannot be used to detect illegal manufacturing where Palmero dairy products are produced by mixing milk from Palmera and Majorera goats, because the c.764G>A SNP segregates in both breeds.

Clarifying the radiative decay of the Hoyle state with charged-particle spectroscopy.

A detailed knowledge of the decay properties of the so called Hoyle state in the 12 C nucleus ( E x = 7.654 MeV, 0 + ) is required to calculate the rate at which carbon is forged in typical red-giant stars. This paper reports on a new almost background-free measurement of the radiative decay branching ratio of the Hoyle state using advanced charged particle coincidence techniques. The exploitation, for the first time in a similar experiment, of a bidimensional map of the coincidence efficiency allows to reach an unitary value and, consequently, to strongly reduce sources of systematic uncertainties. The present results suggest a value of the radiative branching ratio of Γ rad / Γ tot = 4.4 ( 6 ) · 10 - 4 . This finding helps to resolve the tension between recent data published in the literature.

A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen.

The discovery of pharmacogenomic markers in colorectal cancer (CRC) could be setting-specific. FOLFOX4 is employed in the adjuvant and metastatic setting in CRC. This prospective study is aimed to validate in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting (that is, GSTP1-rs947894, and -rs1138272; GSTM1-null genotype; AGXT-rs4426527, -rs34116584 and del-74 bp), and to discover additional markers. CRC patients (n=144) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes. Grade ≥ 2 neurotoxicity was associated (false discovery rate-adjusted q-value <0.1) with single-nucleotide polymorphisms in ABCC1 (rs2074087: odds ratio=0.43(0.22-0.86)), and ABCC2 (rs3740066: 2.99(1.16-7.70); rs1885301: 3.06(1.35-6.92); rs4148396: 4.69(1.60-13.74); rs717620: 14.39(1.63-127.02)). hMSH6-rs3136228 was associated with grade 3-4 neutropenia (3.23(1.38-7.57), q-value=0.0937). XRCC3-rs1799794 was associated with grade 3-4 non-hematological toxicity (8.90(2.48-31.97), q-value=0.0150). The markers previously identified in metastatic CRC were not validated. We have identified new markers of toxicity in genes of transport and DNA repair. If validated in other studies, they could help to identify patients at risk of toxicity.

Parathyroid-gland ultrasonography in clinical and therapeutic evaluation of renal secondary hyperparathyroidism.

PURPOSE: This study evaluated the relationship between ultrasonographic (US) parameters of parathyroid glands (PTGs) in haemodialysis patients (HDP) and degree of secondary hyperparathyroidism (SHPT), therapeutic responsiveness and type of PTG hyperplasia (diffuse or nodular). MATERIALS AND METHODS: In 85 HDP, we evaluated the following US parameters of all and of the largest PTGs: number, maximum longitudinal diameter (MLD), structural (hypoechoic, heterogeneous, nodular) and vascular (nonhypovascular, intermediate, hypervascular) echo-pattern scores. Sixty-nine HDP underwent medical therapy (vitamin D, 39; vitamin D/cinacalcet, 30) and 16 underwent parathyroidectomy. The 69 HDP were classified as responders [median intact parathyroid hormone (iPTH) ≤300 pg/ml during follow-up) or nonresponders (iPTH >300 pg/ml). RESULTS: Number, MLD and structural and vascular echo patterns of PTGs were significantly correlated with iPTH and calcium concentrations. In the 41 (59%) responders, number (0-1), MLD (<10 mm) and structural and vascular scores (1-2) of the largest PTG were significantly lower than in nonresponders. Receiver operating curve (ROC) curve analysis showed high sensitivity and specificity (90% and 73%, respectively) of the MLD (<10mm) of the largest PTG in the predicting therapeutic outcome. US and histological MLD are significantly correlated and predict the type of hyperplasia. CONCLUSIONS: US parameters of PTGs are correlated to the degree of SHPT and type of hyperplasia and predict responsiveness to medical therapy.

Ten-year experience with pharmacogenetic testing for DPYD in a national cancer center in Italy: Lessons learned on the path to implementation.

Background: Awareness about the importance of implementing DPYD pharmacogenetics in clinical practice to prevent severe side effects related to the use of fluoropyrimidines has been raised over the years. Since 2012 at the National Cancer Institute, CRO-Aviano (Italy), a diagnostic DPYD genotyping service was set up. Purpose: This study aims to describe the evolution of DPYD diagnostic activity at our center over the last 10 years as a case example of a successful introduction of pharmacogenetic testing in clinical practice. Methods: Data related to the diagnostic activity of in-and out-patients referred to our service between January 2012 and December 2022 were retrieved from the hospital database. Results: DPYD diagnostic activity at our center has greatly evolved over the years, shifting gradually from a post-toxicity to a pre-treatment approach. Development of pharmacogenetic guidelines by national and international consortia, genotyping, and IT technology evolution have impacted DPYD testing uptake in the clinics. Our participation in a large prospective implementation study (Ubiquitous Pharmacogenomics) increased health practitioners' and patients' awareness of pharmacogenetic matters and provided additional standardized infrastructures for genotyping and reporting. Nationwide test reimbursement together with recommendations by regulatory agencies in Europe and Italy in 2020 definitely changed the clinical practice guidelines of fluoropyrimidines prescription. A dramatic increase in the number of pre-treatment DPYD genotyping and in the coverage of new fluoropyrimidine prescriptions was noticed by the last year of observation (2022). Conclusion: The long path to a successful DPYD testing implementation in the clinical practice of a National Cancer Center in Italy demonstrated that the development of pharmacogenetic guidelines and genotyping infrastructure standardization as well as capillary training and education activity for all the potential stakeholders are fundamental. However, only national health politics of test reimbursement and clear recommendations by drug regulatory agencies will definitely move the field forward.

A modified hypoxia-based TCP model to investigate the clinical outcome of stereotactic hypofractionated regimes for early stage non-small-cell lung cancer (NSCLC).

PURPOSE: Stereotactic body radiotherapy (SBRT) has been applied to lung tumors at different stages and sizes with good local tumor control (LC) rates. The linear quadratic model (LQM), in its basic formulation, does not seem to be appropriate to describe the response to radiotherapy for clinical trials, based on a few fractions. Thus, the main aim of this work was to develop a model, which takes into account the hypoxic cells and their reoxygenation. METHODS: A parameter named B has been introduced in a modified tumor control probability (TCP) from LQM and linear-quadratic-linear model (LQLM), and represents the fraction of hypoxic cells that survive and become oxygenated after each irradiation. Based on published trials evaluating LC at 3 yr (LC3), values of B were obtained by maximum likelihood minimization between predicted TCP and clinical LC3. Two oxygen enhancement ratio (OER) parameter sets (1 and 2) from literature have been adopted to calculate the B-factors. Initial hypoxic cell fractions (η(h)) from 0.05 to 0.50 were assumed. Log-likelihood (L) and Akaike information criterion (AIC) were determined in an independent clinical validation dataset. RESULTS: The B-values of modified TCPs spanned the whole interval from 0 to 1, depending on the fractionation scheme (number of fractions and dose/fraction), showing a maximum (close to 1) at doses/fraction of 8-12 Gy. The B-values calculated using the OER parameter set 1 exhibited a smoother falloff than set 2. An analytical expression was derived to describe the B-value's dependence on the fractionation scheme. The R(2)-adjusted values varied from 0.63 to 0.67 for LQ models and OER set 1 and from 0.75 to 0.78 for LQ model and OER set 2. Lower values of R(2)-adjusted were found for LQLM and both OER sets. L and AIC, calculated using a fraction of η(h) = 0.15 and the B-value from the authors analytical expression were higher than for other η(h)-values, irrespective of model or OER set. CONCLUSIONS: The authors model allows to predict the clinical outcome associated with SBRT treatment, taking into account both direct killing and indirect vasculature or stromal damage.

Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin's lymphoma patients treated with immunochemotherapy.

Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment.

Trigeminal neuralgia as unusual isolated symptom of fungal paranasal sinusitis in patients with haematological malignancies.

A sinonasal infection is a frequent complication in patients with haematological malignancies, and may represent a challenge in terms of differential diagnosis between a bacterial or fungal infective process and tumour localization. A timely and correct diagnosis in these patients is critical and, therefore, may require consultation of specialists outside of haematology; an incorrect diagnosis which underestimates the seriousness of the infection can be fatal. Symptomatic trigeminal neuralgia resulting from direct compression or perineural invasion from malignancy is not uncommon in the literature. However, trigeminal neuralgia as an isolated symptom at the onset of a bacterial or invasive fungal sinusitis is rare and risks going unnoticed. The authors herein describe three cases of patients affected by acute myeloid leukaemia or lymphoma in which an invasive fungal sinusitis appeared at the onset as an isolated trigeminal neuralgia, with pain located along the distribution area of the second branch of the trigeminal nerve. Only after referring these patients to a neurologist for a host of neurological exams it was possible to confirm a diagnosis of secondary maxillary sinus fungal involvement.

Acoustic radiation force impulse (ARFI) imaging with Virtual Touch Tissue Quantification in liver disease associated with cystic fibrosis in children.

PURPOSE: Cystic-fibrosis-associated liver disease (CFLD) may lead to portal hypertension (PHT) and cirrhosis. Clinical signs and biochemistry of liver involvement are not discriminating. The aim of the study was to evaluate the performance of acoustic radiation force impulse (ARFI) with virtual tissue quantification in comparison with clinical signs, biochemistry and standard hepatic ultrasound (US) patterns. MATERIALS AND METHODS: Virtual Touch Tissue Quantification, an implementation of US ARFI with shear-wave velocity (SWV) measurements was used in 75 children with cystic fibrosis (CF) and suspected CFLD to quantify hepatic stiffness. In each patient, ten measurements of SWV were performed on the right hepatic lobe. Patients were also evaluated by standard diagnostic tools (standard US, liver- and lung function tests, oesophagogastroscopy). RESULTS: Among CF patients, median SWV was significantly higher in patients with clinical, biochemical and US signs of hepatic involvement than in patients without US evidence of liver disease 1.08 m/s [(95% confidence interval (CI), 1.02-1.14]. Median SWV values in patients with portal hypertension, splenomegaly and oesophageal varices were 1.30 (95% CI, 1.17-1.43), 1.54 (95% CI, 1.32-1.75) and 1.63 (95% CI, 1.26-1.99), respectively. Differences were significant (p<0.001). CONCLUSIONS: ARFI is an innovative screening technique able to help identify CFLD in children.

Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

Proteus mirabilis isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase bla(CMY) genes from a Citrobacter freundii origin (bla(CMY-2)-like genes). Isolates from Poland harbored several bla(CMY) genes (bla(CMY-4), bla(CMY-12), bla(CMY-14), bla(CMY-15), and bla(CMY-38) and the new gene bla(CMY-45)), while isolates from Italy and Greece harbored bla(CMY-16) only. Earlier isolates with bla(CMY-4) or bla(CMY-12), recovered in France from Greek and Algerian patients, were also studied. All isolates showed striking similarities. Their bla(CMY) genes resided within ISEcp1 transposition modules, named Tn6093, characterized by a 110-bp distance between ISEcp1 and bla(CMY), and identical fragments of both C. freundii DNA and a ColE1-type plasmid backbone. Moreover, these modules were inserted into the same chromosomal site, within the pepQ gene. Since ColE1 plasmids carrying ISEcp1 with similar C. freundii DNA fragments (Tn6114) had been identified earlier, it is likely that a similar molecule had mediated at some stage this DNA transfer between C. freundii and P. mirabilis. In addition, isolates with bla(CMY-12), bla(CMY-15), and bla(CMY-38) genes harbored a second bla(CMY) copy within a shorter ISEcp1 module (Tn6113), always inserted downstream of the ppiD gene. Sequence analysis of all mobile bla(CMY-2)-like genes indicated that those integrated in the P. mirabilis chromosome form a distinct cluster that may have evolved by the stepwise accumulation of mutations. All of these observations, coupled to strain typing data, suggest that the bla(CMY) genes studied here may have originated from a single ISEcp1-mediated mobilization-transfer-integration process, followed by the spread and evolution of a P. mirabilis clone over time and a large geographic area.

Muscle transcriptome profiling in divergent phenotype swine breeds during growth using microarray and RT-PCR tools.

Using an array consisting of 10 665 70-mer oligonucleotide probes, the longissimus dorsi muscle tissue expression during growth in nine pigs belonging to Casertana (CT), an autochthonous breed characterized by slow growth and a massive accumulation of backfat, was compared with that of two cosmopolitan breeds, Large White (LW) and a crossbreed (CB; Duroc × Landrace × Large White). The results were validated by real-time PCR. All animals were of the same age and were raised under the same environmental conditions. Muscle tissues were collected at 3, 6, 9 and 11 months of age, and a total of 173 genes showed significant differential expression between CT and the cosmopolitan genetic types at 3 months of age. Time series cluster analysis indicated that the CT breed had a different pattern of gene expression compared with that of the LW and the CB. Four of the eight clusters highlighted the gene differences between CT and the other two breeds, which were further supported by statistical analyses: clusters 4 and 5 contained a total of 71 genes that were underexpressed at 3 months of age, and cluster 3 and cluster 7 included 28 and 42 genes respectively that were overexpressed at 3 months of age. As expected, differentially expressed genes belonged to the category of genes coding for contractile fibres and transcription factors involved in muscle development and differentiation. These findings highlight muscle expression genes during pig growth and are useful to understand the genetic meaning of the different developmental rates.

Polymorphism of the goat agouti signaling protein gene and its relationship with coat color in Italian and Spanish breeds.

Agouti signaling protein (ASIP) is one of the key players in the modulation of hair pigmentation in mammals. Binding to the melanocortin 1 receptor, ASIP induces the synthesis of phaeomelanin, associated with reddish brown, red, tan, and yellow coats. We have sequenced 2.8 kb of the goat ASIP gene in 48 individuals and identified two missense (Cys126Gly and Val128Gly) and two intronic polymorphisms. In silico analysis revealed that the Cys126Gly substitution may cause a structural change by disrupting a highly conserved disulfide bond. We studied its segregation in 12 Spanish and Italian goat breeds (N = 360) with different pigmentation patterns and found striking differences in the frequency of the putative loss-of-function Gly(126) allele (Italian 0.43, Spanish Peninsular 0.08), but we did not observe a clear association with coat color. This suggests that the frequency of this putative loss-of-function allele has evolved under the influence of demographic rather than selection factors in goats from these two geographical areas.

Vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger.

BACKGROUND: The artery of Wollschlaeger and Wollschlaeger is a tentorial branch of the superior cerebellar artery: due to its small diameter, it is not usually seen in normal angiograms except when enlarged in the setting of a dural AVF or tentorial meningioma. Its presence has been rarely described in the Literature. CASE REPORT: herein we describe the first ever reported case of a vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger in 70 year old female patient. CONCLUSION: vermian subtentorial AVMs supplied by the artery of Wollschlaeger and Wollschlaeger are extremely rare vascular malformations. The presence of the artery of Wollschlaeger and Wollschlaeger must be carefully evaluated during preoperative surgical planning due to its key role in the supply of vascular malformation and to decrease the risk of intra operative bleeding during surgery.

The problem with implementing fish farms in agricultural regions: A trial in a pampean pond highlights potential risks to both human and fish health.

The safety of creating fish farms in agricultural settings was evaluated by growing Piaractus mesopotamicus in a pond, while crops where cultivated in a nearby field under a pesticide application regime typical of the Pampa region. Atrazine, glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), were detected in the water of the pond at concentrations ranging between 92 and 118 µg/L for atrazine, 12 and 221 µg/L for glyphosate and 21 and 117 µg/L for AMPA. Atrazine and malathion were detected in fish muscles at concentrations ranging between 70 and 105 µg/kg for atrazine and 8.6 and 23.7 µg/kg for malathion. Compared to fish raised in a pisciculture, fish from the agricultural pond presented reduced values of pack cell volume, hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, together with significantly greater cholinesterase activity in both plasma and liver and reduced glutathione-S-transferase activity in the liver. A comet assay also demonstrated that P. mesopotamicus from the agricultural pond presented a significantly greater level of DNA damage in both erythrocytes and gill cells. Overall, the present study demonstrates that pisciculture ponds established in an agricultural setting may receive pesticides applied to nearby cultures and that these pesticides may be taken up by the fish and affect their physiology and health. The accumulation of pesticides residues in fish flesh may also present a risk to human consumers and should be closely controlled.