Mass Spectrometry for Diabetic Nephropathy Monitoring: New Effective Tools for Physicians

The main aim of diabetic nephropathy monitoring is to identify molecular markers, that is, to find changes occurring at metabolome and proteome levels indicative of the disease's development. The mass spectrometry methods available today have been successfully applied to this field. This paper provides a short description of the basic aspects of the mass spectrometric methods used for diabetic nephropathy monitoring, reporting and discussing the results obtained using different approaches

A Survey on the characteristics of sausage made from Sicilian and Sardinian native pigs

Four different mixtures were prepared using meat from native pigs. Mixtures 1 and 2 were made in Sardinia using meat from pigs of Sarda breed, mixtures 3 and 4 in Sicily, using meat from the Nera Siciliana breed. The manufacturing were different not only for the typology of the meat but also for the meat cuts used and the ingredients. Batches 1 and 3 were made in non conditioned natural environments, while batches 2 and 4 in conditioned environments. Chemical-physical and microbiological analyses were carried out on the fresh mixture, after 7 days of ripening (end of drying in conditioned environment and at the end of seasoning (28 days). The thermoigrometric environmental parameters and the variation in the weight of the production were measured during ripening. Regarding the Lactic Acid Bacteria and the Micrococcaceae, microorganisms of normal maturation, a rapid development, except for batch 1, was observed for all batches at 7 days of ripening. In batches 2 and 4 an increase of Enterobacteriaceae in the drying phase and a their decrease in the seasoning phase were noticed. In batch 3 their inactivation resulted slow. Such occurrences were probably due to the hygienic conditions and non inhibiting technological parameters. The initial humidity was less than 60% with the exception of batch 3; the quantity of NaCl ranged between 2 and 2.8%. The amount of fat varied between 14 and 24% at the beginning of the ripening, then reached values ranging between of 20 and 38% at the end of the seasoning phase. All the batches showed a decrease of aw included between 0.97 (mixture) and 0.87 (final product); the highest value of aw recorded in test 1 was attributable to the lower T recorded both during the drying and seasoning phase. The pH reached the lowest values at the end of the 7 days and then increased, with the exception of batch 3, which decreased during the whole seasoning phase

Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte α268Asn→Lysβ262Ala→Pro)

We report the first case of cosegregation of two haemoglobins (Hbs): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested

Safety and efficacy of direct-acting antivirals in transfusion-dependent thalassemic patients with chronic hepatitis C

Background: Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassemic patients. New treatments based on direct-acting antivirals (DAAs) are highly effective and well-tolerated by patients; nonetheless, they have not been studied in thalassemic populations. In this study, we evaluated the safety and efficacy of these treatments in a cohort of Sardinian thalassemic patients with chronic HCV infection. Methods: We consecutively recruited thalassemic patients with HCV infection, who were eligible for DAA therapy at 3 liver units. Different drug combinations, depending on HCV genotype and hepatic disease severity, were used according to the current guidelines. Sustained virological response was assessed at 12 weeks posttreatment. Data regarding the side effects and transfusion requirements were also collected. Results: We recruited 49 patients, including 29 males (59.2%), with the mean age of 43 years (genotype 1, 55.1%). Twenty-one (42.9%) patients had a history of interferon-based treatment. Cirrhosis was detected in 28 (57.1%) patients; only 1 patient had ascites and hypoalbuminemia (Child-Pugh B7). On the other hand, 35 (71.4%) patients received a sofosbuvir-based regimen. Ribavirin treatment was reported in 26 (53.1%) cases. All the patients were followed-up for at least 12 weeks after therapy, and sustained virological response was observed in 98% of the patients. No treatment discontinuation was required due to adverse events. The most common side effects included fatigue (24.5%), headache (10.2%), and anaemia (77%), requiring further blood transfusion in patients receiving ribavirin. Conclusions: This prospective study showed that DAAs are safe and effective agents in thalassemic patients with advanced liver fibrosis, regardless of previous antiviral treatment responses

Recenti indagini alla necropoli fenicia di Pani Loriga

This work considers the results of the excavation of Tomb 2016B in the Phoenician necropolis at Pani Loriga (Santadi, Sardinia). A multidisciplinary methodology was adopted, involving different professional figures, from geologists to archaeologists, anthropologists, palaeobotanists and chemists. Object of the analysis is a double grave in an elongated rectangular pit cut into a rhyolite bed. The inhumation rite – very rare at Pani Loriga, where cremation predominates –, the monumental type of tomb, with a cover of worked slabs resting on ledges and two symmetrical cavities at the bottom of the pit near the short sides, and the funerary vases allow us to link Tomb 2016B to Tomb 33, excavated in the last century by Ferruccio Barreca, and to a group of Monte Sirai burials, including Tomb 88, the suggested burial place of a person from Carthage. In fact, the new discoveries highlight the movement – in the first half of the 6th c. BC – of wealthy individuals, probably merchants, from the Gulf of Tunis area to central and south-western Sardinia.Peer reviewe

The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH). Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy). ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D' = 0.92 vs D' = 0.50 respectively; P = 1.3x10(-8)). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 - 17.4) U/mL vs 21.3 (16.5 - 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 - 44.8) U/mL vs 8.8 (6.1 - 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies. ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms