Presence of prednisolone in complementary feedstuffs for bovine husbandry

BACKGROUND: According to European Union legislation, prednisolone, a steroid that belongs to the glucocorticosteroid group, is banned as a growth promoter in cattle husbandry and therefore should not be present in bovine feedstuffs. As our preliminary investigations detected prednisolone in this matrix, we performed a study on different commercially available complementary feedstuffs, stored at the farm and/or in the laboratory, in order to verify whether its presence was due to neo-formation during storage. RESULTS: Prednisolonewas detected in almost all (95%) feedstuffs collected at the farm.When the feedstuffswere stored at the laboratory, the frequency (31%) and the concentration of prednisolone-positiveswere lower. This difference, which is likely due to different environmental conditions, implies the possibility of its neo-formation. CONCLUSION: Our data indicate that the neo-formation of prednisolone can occur in feedstuff, and that the frequency and concentration could be related to the storage conditions. The individuation of an objective parameter that is useful for the identification of the compliance of feed is therefore essential

SORL1 mutation in a Greek family with Parkinson's disease and dementia

Whole exome sequencing and linkage analysis were performed in a three generational pedigree of Greek origin with a broad phenotypic spectrum spanning from Parkinson’s disease and Parkinson’s disease dementia to dementia of mixed type (Alzheimer disease and vascular dementia). We identified a novel heterozygous c.G1135T (p.G379W) variant in SORL1 which segregated with the disease in the family. Mutation screening in sporadic Greek PD cases identified one additional individual with the mutation, sharing the same 12.8Mb haplotype. Our findings provide support for SORL1 mutations resulting in a broad range of additional phenotypes and warrants further studies in neurodegenerative diseases beyond AD

Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (<it>MAPT</it>), progranulin (<it>PGRN</it>) and charged multi-vesicular body protein 2B (<it>CHMP2B</it>) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of <it>MAPT </it>has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate <it>MAPT </it>mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland.</p> <p>Methods</p> <p><it>MAPT </it>exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and <it>MAPT </it>haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls.</p> <p>Results</p> <p>No pathogenic mutations were found. The H2 allele frequency was 11.0% (<it>P </it>= 0.028) in the FTLD patients, 9.8% (<it>P </it>= 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (<it>P </it>= 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD.</p> <p>Conclusion</p> <p>We conclude that although pathogenic <it>MAPT </it>mutations are rare in Northern Finland, the <it>MAPT </it>H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.</p

Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis

<p>Abstract</p> <p>Background</p> <p>The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis.</p> <p>Methods</p> <p>Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 ± 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index ≥ 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect.</p> <p>Results</p> <p>In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index ≥ 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index ≥ 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27).</p> <p>Conclusions</p> <p>The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.</p

Association of CETP TaqI and APOE polymorphisms with type II diabetes mellitus in North Indians: a case control study

BACKGROUND: Genetic variants of proteins involved in lipid metabolism may play an important role in determining the susceptibility for complications associated with type II diabetes mellitus (T2DM). Goal of the present study was to determine the association of cholesteryl ester transfer protein TaqI B, D442G, and APOE Hha I polymorphisms with T2DM and its complications. METHODS: Study subjects were 136 patients and 264 healthy controls. All polymorphisms were detected using PCR-RFLP and statistical analysis done with χ(2 )test and ANOVA. RESULTS: Although CETP TaqI B polymorphism was not associated with the T2DM, yet B1B2 genotype was significantly (p = 0.028) associated with high risk of hypertension in diabetic patients (OR = 3.068, 95% CI 1.183–7.958). In North Indians D442G variation in CETP gene was found to be absent. Frequency of APOE HhaI polymorphism was also not different between patients and controls. In diabetic patients having neuropathy and retinopathy significantly different levels of total-cholesterol [(p = 0.001) and (p = 0.029) respectively] and LDL-cholesterol [(p = 0.001) and (p = 0.001) respectively] were observed when compared to patients with T2DM only. However, lipid levels did not show any correlation with the CETP TaqI B and APOE Hha I genetic polymorphisms. CONCLUSION: CETP TaqI B and APOE HhaI polymorphism may not be associated with type II diabetes mellitus in North Indian population, however CETP TaqI B polymorphism may be associated with hypertension along with T2DM

PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.

OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225-240

DataSheet1_Correlation between small earthquakes and CO2 anomalies in spring waters: a statistical experiment on the probability of seismic occurrence.PDF

We correlated carbon dioxide (CO2) time series detected at the Gallicano site in Tuscany, Italy, with low-magnitude earthquakes occurred in the surrounding area between 2017 and 2021. The CO2 irregular component distribution was analyzed by a Pearson type VII fit, and its cumulate probability by the Gauss’s hypergeometric function, to statistically evidence anomalous fluctuations. We calculated the Matthews correlation between gas concentrations and low-magnitude earthquakes by defining a binary occurrence of CO2 anomalies and seismic events. A positive correlation was highlighted by a time lag between the digital series, which resulted in CO2 anomaly detections ahead of the earthquake time of two days. The correlated earthquakes were mainshocks of local magnitude 1.2 to 3.6, with epicenters within 40 km from the Gallicano site. Correlations among rainfalls, CO2 concentrations and earthquakes were also considered, showing that only few rainfall events were followed by a CO2 anomaly, mostly a day late.</p

A case of fatal intoxication from Metformin

ABSTRACT: A case of fatal intoxication from metformin is presented. The decedent was an obese 58-year-old-woman with type II diabetes, in whom severe lactic acidosis secondary to metformin accumulation was precipitated by acute renal failure. She had been on metformin 500 mg twice a day. Postmortem blood was deproteinated with acetonitrile, washed with dichloromethane, and the resulting supernatant injected into high-performance liquid chromatography system. Separation was performed on a analytical 125 · 4 mm i.d. RP-8 column. The wavelength was set at 235 nm. The mobile phase was acetonitrile (40%), sodium lauryl sulfate, and sodium dihydrogen phosphate adjusted to pH 5.1 (60%) at a flow rate of 1.0 mL⁄ min. The concentration of metformin in postmortem blood was 77.3 lg ⁄ mL. The qualitative result was also confirmed by LC⁄APCI ⁄MS⁄MS analysis

Association of NFKB1, NKX2-5, GATA4 and RANKL gene polymorphisms with sporadic congenital heart disease in Greek patients

Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the NFKB1 gene polymorphism (–94ins/ delATTG), rs28362491, NKX2-5 gene polymorphism rs2277923, GATA4 gene polymorphism rs11785481 and RANKL gene polymorphism rs4531631. A total of 43 CHD patients and 100 healthy adults were included in the study. The polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) method was used to genotype the aforementioned polymorphisms of NFKB1, NKX2-5, GATA4 and RANKL. The association analysis identified that there was a protective association between CHD and the A allele of rs2277923 polymorphism (p = 0.004). The D allele of the rs28362491 polymorphism is also a likely risk factor for causing CHD (p = 0.006). The differences of the rs4531631 and rs11785481 variant contribution had no statistical significance between the groups (p >0.05). In conclusion, our results revealed that the rs28362491 and rs2277923 gene polymorphisms, but not the rs4531631 and rs11785481 polymorphisms, may contribute to CHD risk in a cohort of Greek CHD patients