The detection of regions that affect quantitative traits (QTL), to implement selection assisted by molecular information, remains of particular interest in dairy sheep for which genetic gain is ...constrained by the high costs of large-scale phenotype and pedigree recording. QTL detection based on the combination of linkage disequilibrium and linkage analysis (LDLA) is the most suitable approach in family-structured populations. The main issue in performing LDLA mapping is the handling of the identity-by-descent (IBD) probability matrix. Here, we propose the use of principal component analysis (PCA) to perform LDLA mapping for milk traits in Sarda dairy sheep.
A resource population of 3731 ewes belonging to 161 sire families and genotyped with the OvineSNP50 Beadchip was used to map genomic regions that affect five milk traits. The paternally and maternally inherited gametes of genotyped individuals were reconstructed and IBD probabilities between them were defined both at each SNP position and at the genome level. A QTL detection model fitting fixed effects of principal components that summarize IBD probabilities was tested at each SNP position. Genome-wide (GW) significance thresholds were determined by within-trait permutations.
PCA resulted in substantial dimensionality reduction, in fact 137 and 32 (on average) principal components were able to capture 99% of the IBD variation at the locus and genome levels, respectively. Overall, 2563 positions exceeded the 0.05 GW significance threshold for at least one trait, which clustered into 75 QTL regions most of which affected more than one trait. The strongest signal was obtained for protein content on Ovis aries (OAR) chromosome 6 and overlapped with the region that harbours the casein gene cluster. Additional interesting positions were identified on OAR4 for fat content and on OAR11 for the three yield traits.
PCA is a good strategy to summarize IBD probabilities. A large number of regions associated to milk traits were identified. The outputs provided by the proposed method are useful for the selection of candidate genes, which need to be further investigated to identify causative mutations or markers in strong LD with them for application in selection programs assisted by molecular information.
Aims
Although increasingly recognized as a distinct pathological entity, left bundle branch block‐induced cardiomyopathy (LBBB‐ICMP) is not included among the possible aetiologies of acquired dilated ...cardiomyopathies (DCM). While diagnostic criteria have been proposed, its recognition remains principally retrospective, in the presence of clinical and instrumental red flags. We aimed to assess the prevalence and clinical and instrumental features of LBBB‐ICMP in a large cohort of patients with DCM.
Methods and results
We analysed a cohort of 242 DCM patients from a two‐centre registry. Inclusion criteria were age > 18, non‐ischaemic or non‐valvular DCM, and LBBB on electrocardiogram. LBBB‐ICMP was defined according to previously proposed diagnostic criteria: (i) neither family history nor clinically identifiable potential causes for DCM; (ii) negative genetic testing; (iii) echocardiographic features including non‐severe chamber dilation, normal absolute and relative wall thickness, marked dyssynchrony, and normal right ventricular function; and (iv) absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). From the entire cohort, we identified 30 subjects (similar in terms of New York Heart Association class I or II in 80% vs. 75%, P = 0.56; QRS width of 150 ± 22 vs. 151 ± 24 ms, P = 0.82; and cardiac remodelling of baseline end‐diastolic diameter 66 ± 8 vs. 65 ± 10 mm, P = 0.53) with a comprehensive dataset including CMR and genetic testing, required to verify the presence of the diagnostic criteria proposed for LBBB‐ICMP. The main characteristics of this subgroup were 73% males, age 45 ± 13 years, left ventricular ejection fraction (LVEF) 30 ± 10%, LGE in 38% of patients, and QRS complex of 150 ± 22 ms. Patients were under guideline‐directed medical therapy, and 57% of them were treated with cardiac resynchronization therapy (CRT). Two patients (6.67%, 50% males, age 53 ± 13 years) fulfilled the diagnostic criteria proposed for LBBB‐ICMP. After a follow‐up of 44 (12–76) months, LVEF was normal and QRS width significantly reduced (from 154 ± 25 to 116 ± 52 ms) in patients with LBBB‐ICMP. Both patients were under optimal medical treatment, and one was implanted with CRT‐D. Neither of the two patients experienced death, malignant ventricular arrhythmia, or heart failure hospitalization at follow‐up.
Conclusions
Left bundle branch block‐induced cardiomyopathy emerges as a distinct pathological entity, promptly identifiable in a minority but not negligible proportion of patients with newly diagnosed DCM and LBBB, using a series of diagnostic criteria including CMR and genetic testing. Further studies are needed to better elucidate the clinical course of LBBB‐ICMP.
This study aimed to evaluate the effects of different feedings on main traits and polar and semi-polar metabolite profiles of ovine milk. The milk metabolome of two groups of Sarda sheep kept under ...different grazing systems were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and multivariate statistical analysis (MVA). The results of discriminant analysis indicated that the two groups showed a different metabolite profile, i.e., milk samples of sheep kept under Grazing System 1 (GS1) were richer in nucleosides, inositols, hippuric acid, and organic acids, while milk of sheep under Grazing System 2 (GS2) showed higher levels of phosphate. Statistical analysis of milk main traits indicates that fat content was significantly higher in GS1 samples while milk from GS2 sheep had more urea, trans-vaccenic acid, and rumenic acid. MVA studies of the associations between milk main traits and metabolite profile indicated that the latter reflects primarily the long chain fatty acid content, the somatic cell count (SCC), and lactose levels. All together, these results demonstrated that an integrated holistic approach could be applied to deepen knowledge about the effects of feeding on sheep’s milk composition.
Background:
The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, ...serological tests became routinely available.
Objective:
To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test.
Methods:
We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model.
Results:
Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002).
Conclusion:
Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
Background and purpose
Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID‐19) have been thoroughly investigated, but a further analysis on main signs ...and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID‐19 in MS patients and identify all factors associated with their manifestation.
Method
Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.
Results
From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID‐19. Ageusia and anosmia was less frequent in older people (odds ratio OR 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease‐modifying therapies were associated with greater frequencies of certain COVID‐19 symptoms (association between anti‐CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu‐like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta.
Conclusion
Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID‐19 symptoms.
It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the ...outcomes expected in the age- and sex-matched Italian population.
Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale EDSS score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ
test, and the risk excess was quantified by risk ratios (RRs).
The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (
< 0.001), RR = 2.19 for ICU admission (
< 0.001), and RR = 2.43 for death (
< 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03,
= 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events,
= 0.04).
Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.
Background and purpose
Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well ...as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS.
Methods
Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity.
Results
In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009).
Conclusions
Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated.
Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.
The objective of the study was to measure N volatilisation (NVOL) from bedded-pack dairy cow barns. Feed intake, milk production, bedding material used and meteorological variables were monitored in ...3 dairy farms near the town of Arborea (39°46'26" N, 08°34'53" E, 7 m a.s.l.) during one month for each season from summer 2007 to spring 2008. NVOL was measured in the interval between excretion and removal of bedded-packs from barn floors. NVOL was measured using the N (nitrogen) to P (phosphorus) ratio marker method, considering P as an internal non-volatile marker in milk and manure. Nitrogen and P excretion was estimated by nutrient balance as intake minus N and P excreted in milk. NVOL coefficient and bad-pack temperature were almost constant among seasons. The annual mean NVOL in bedded-pack barns was equal to 38.8% of excreted N. Accounting also for the NVOL that occurred in the concrete floor of the feeding and walking areas ofthe barns, NVOL was 40.7% of N excreted.
The sarcophagus containing the remains of Federico II, located in the Cathedral of Palermo (Sicily, Italy), was opened on 1998 to perform a multidisciplinary survey 1. Next to the remains of Federico ...II and in close contact with them were laying two other skeletons belonging, according to historical records, to Pietro II di Aragona and to an anonymous person (“The Third Individual”), probably a woman. The bones appeared severely deteriorated. Chemical analysis performed on bone samples excluded that the bodies underwent some kind of embalming process. The analysis of mtDNA from bone samples taken from the three skeletons was successful in only one of the two labs involved. The HVR1-mtDNA sequence (region: from nt 16,035 to nt 16,395), obtained from the bone samples of Federico II and “The Third Individual” appear identical but bear double peaks at the same nucleotide positions, suggesting mixing (i.e. contamination) of different mtDNA types. The HVR1 sequence obtained from the bone sample of Pietro II di Aragona does not present double peaks and differ from the Cambridge Reference Sequence (CRS) at six nucleotide positions. Cloning experiment of the Federico II amplicon demonstrated that the mixed mtDNA types are only two: one identical to CRS, the other identical to the sequence of Pietro II di Aragona. A reconstruction of these data are proposed in the Discussion. Due to the problematic context in which this study was carried out (mixed and deteriorated biological material, failure to replicate results in two different labs), our results and reconstruction can only be offered on a tentative basis. It is hoped that the data presented in this study will reveal useful, for future comparison, if further molecular genetics research will be carried out on the royal dynasties that ruled Sicily in the early centuries of the past millennium.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social interaction and communication, with restricted interests, activity and behaviors. ASD is highly familial, ...indicating that genetic background strongly contributes to the development of this condition. However, only a fraction of the total number of genes thought to be associated with the condition have been discovered. Moreover, other factors may play an important role in ASD onset. In fact, it has been shown that parental conditions and in utero and perinatal factors may contribute to ASD etiology. More recently, epigenetic changes, including DNA methylation and micro RNA alterations, have been associated with ASD and proposed as potential biomarkers. This review aims to provide a summary of the literature regarding ASD candidate genes, mainly focusing on synapse formation and functionality and relevant epigenetic and environmental aspects acting in concert to determine ASD onset.
PDF
