Noise in multiple sclerosis: unwanted and necessary

As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression “noise”) can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy

Determination of milk production losses and variations of fat and protein percentages according to different levels of somatic cell count in Valle del Belice dairy sheep

The somatic cell count (SCC) of milk is widely used to monitor udder health and the milk quality and because of its positive genetic correlation with mastitis this trait was included in breeding schemes of dairy sheep. The aim of this study was to estimate the loss in milk yield (MY) and related composition resulting from different levels of somatic cell count in Valle del Belice dairy sheep. Data were collected between 2006 and 2016 in 15 flocks following an A4 recording scheme. Somatic cell count (SCC), fat and protein percentage (F% and P%) were determined using mid-infrared spectroscopy. To evaluate loss in test day MY, F% and P%, five different classes of SCC were arbitrarily defined: SCC1 ⤠500 à 103, 500 à 103 2000 à 103. To estimate the loss of milk production and quality a linear model, with test day milk production traits as dependent variable, was used. Furthermore, the effect of order of parity and season of lambing were investigated to study the effects on milk production traits. Least squares means were computed for milk production traits and the differences between means were determined by Fischer's least significant difference. The estimated losses in MY according to the level of used SCC were approximately 16% whereas there was an increase of 0.06% and 0.29% for fat and protein percentage, respectively. Apart from environmental factors and management, this study confirms that high levels of somatic cell count in sheep milk are associated with milk yield losses and changes in milk composition. Results suggest that it is necessary to implement a program aimed to reduce the milk somatic cell count in ewes' milk, with the aim of improving the quality of ewes' milk and dairy products

Detection of genomic regions underlying milk production traits in Valle del Belice dairy sheep using regional heritability mapping

The aim of this study was to identify genomic regions underlying milk production traits in the Valle del Belice dairy sheep using regional heritability mapping (RHM). Repeated measurements for milk yield (MY), fat percentage and yield (F% and FY) and protein percentage and yield (P% and PY), collected over a period of 6 years (2006-2012) on 481 Valle del Belice ewes, were used for the analysis. Animals were genotyped with the Illumina 50k SNP chip. Variance components, heritabilities and repeatabilities within and across lactations were estimated, fitting parity, litter size, season of lambing and fortnights in milk, as fixed; and additive genetic, permanent environment within and across lactations, flock by test-day interaction and residual as random effects. For the RHM analysis, the model included the same fixed and random effects as before, plus an additional regional genomic additive effect (specific for the region being tested) as random. While the whole genomic additive effect was estimated using the genomic relationship matrix (GRM) constructed from all SNPs, the regional genomic additive effect was estimated from a GRM matrix constructed from the SNPs within each region. Heritability estimates ranged between 0.06 and 0.15, with repeatabilities being between 0.14 and 0.24 across lactations and between 0.23 and 0.39 within lactation for all milk production traits. A substantial effect of flock-test-day on milk production traits was also estimated. Significant genomic regions at either genome-wide (p < .05) or suggestive (i.e., one false positive per genome scan) level were identified on chromosome (OAR) 2, 3 and 20 for F% and on OAR3 for P%, with the regions on OAR3 in common between the two traits. Our results confirmed the role of LALBA and AQP genes, on OAR3, as candidate genes for milk production traits in sheep

Genome-wide association study between CNVs and milk production traits in Valle del Belice sheep

Copy number variation (CNV) is a major source of genomic structural variation. The aim of this study was to detect genomic CNV regions (CNVR) in Valle del Belice dairy sheep population and to identify those affecting milk production traits. The GO analysis identified possible candidate genes and pathways related to the selected traits. We identified CNVs in 416 individuals genotyped using the Illumina OvineSNP50 BeadChip array. The CNV association using a correlation-trend test model was examined with the Golden Helix SVS 8.7.0 tool. Significant CNVs were detected when their adjusted p-value was <0.01 after false discovery rate (FDR) correction. We identified 7,208 CNVs, which gave 365 CNVRs after aggregating overlapping CNVs. Thirty-one CNVRs were significantly associated with one or more traits included in the analysis. All CNVRs, except those on OAR19, overlapped with quantitative trait loci (QTL), even if they were not directly related to the traits of interest. A total of 222 genes were annotated within the significantly associated CNVRs, most of which played important roles in biological processes related to milk production and health-related traits. Identification of the genes in the CNVRs associated with the studied traits will provide the basis for further investigation of their role in the metabolic pathways related to milk production and health traits

Ilioinguinal nerve neurectomy is better than preservation in lichtenstein hernia repair. A systematic literature review and meta-analysis

Objective This study aimed to evaluate the incidence of chronic groin pain (primary outcome) and alterations of sensitivity (secondary outcome) after Lichtenstein inguinal hernia repair, comparing neurectomy with ilioinguinal nerve preservation surgery. Summary background data The exact cause of chronic groin postoperative pain after mesh inguinal hernia repair is usually unclear. Section of the ilioinguinal nerve (neurectomy) may reduce postoperative chronic pain. Methods We followed PRISMA guidelines to identify randomized studies reporting comparative outcomes of neurectomy versus ilioinguinal nerve preservation surgery during Lichtenstein hernia repairs. Studies were identified by searching in PubMed, Scopus, and Web of Science from April 2020. The protocol for this systematic review and meta-analysis was submitted and accepted from PROSPERO: CRD420201610. Results In this systematic review and meta-analysis, 16 RCTs were included and 1550 patients were evaluated: 756 patients underwent neurectomy (neurectomy group) vs 794 patients underwent ilioinguinal nerve preservation surgery (nerve preser- vation group). All included studies analyzed Lichtenstein hernia repair. The majority of the new studies and data comes from a relatively narrow geographic region; other bias of this meta-analysis is the suitability of pooling data for many of these studies. A statistically significant percentage of patients with prosthetic inguinal hernia repair had reduced groin pain a 6 months after surgery at 8.94% (38/425) in the neurectomy group versus 25.11% (113/450) in the nerve preservatio group [relative risk (RR) 0.39, 95% confidence interval (CI) 0.28–0.54; Z = 5.60 (P 0.00001)]. Neurectomy did no significantly increase the groin paresthesia 6 months after surgery at 8.5% (30/353) in the neurectomy group versu 4.5% (17/373) in the nerve preservation group [RR 1.62, 95% CI 0.94–2.80; Z = 1.74 (P = 0.08)]. At 12 months afte surgery, there is no advantage of neurectomy over chronic groin pain; no significant differences were found in th 12-month postoperative groin pain rate at 9% (9/100) in the neurectomy group versus 17.85% (20/112) in the inguina nerve preservation group [RR 0.50, 95% CI 0.24–1.05; Z = 1.83 (P = 0.07)]. One study (115 patients) reported dat about paresthesia at 12 months after surgery (7.27%, 4/55 in neurectomy group vs. 5%, 3/60 in nerve preservatio group) and results were not significantly different between the two groups [RR 1.45, 95% CI 0.34, 6.21;Z = 0.5 (P = 0.61)]. The subgroup analysis of the studies that identified the IIN showed a significant reduction of the 6th mont evaluation of pain in both groups and confirmed the same trend in favor of neurectomy reported in the previous overal analysis: statistically significant reduction of pain 6 months after surgery at 3.79% (6/158) in the neurectomy grou versus 14.6% (26/178) in the nerve preservation group [RR 0.28, 95% CI 0.13–0.63; Z = 3.10 (P = 0.002)]. Conclusion Ilioinguinal nerve identification in Lichtenstein inguinal hernia repair is the fundamental step to reduce or avoid postoperative pain. Prophylactic ilioinguinal nerve neurectomy seems to offer some advantages concerning pain in the first 6th month postoperative period, although it might be possible that the small number of cases contributed to the insignificancy regarding paresthesia and hypoesthesia. Nowadays, prudent surgeons should discuss with patients and their families the uncertain benefits and the potential risk of neurectomy before performing the hernioplasty

Effect of Mycoplasma agalactiae mastitis on milk production and composition in Valle dell Belice dairy sheep

Contagious agalactia (CA), a disease caused by Mycoplasma agalactiae and other pathogenic mycoplasmas, is a well-known multietiological syndrome affecting dairy breeds of sheep and goats in the Mediterranean basin. The aim of this work was to study the effect on milk production and composition of mastitis caused by M. agalactiae in Valle del Belice dairy sheep. All ewes were manually milked twice daily and the milk from both daily milking was analysed for milk composition and somatic cell counts. Moreover the morning milk samples were collected aseptically from each animal for bacteriological analyses. A mixed linear model was utilised to consider milk production and composition between animals infected by CA and healthy animals. After bacteriological investigation using both cultural and molecular methods, 37 ewes were found to be infected by M. agalactiae while 50 uninfected ewes were randomly selected from the same herds to compare milk production and composition between infected and healthy animals. Statistical analyses showed that the infection with M. agalactiae had a significant effect on yield and some milk components. In particular, infected ewes showed lower milk production with lower lactose content and higher somatic cell counts. The implementation of disease control programmes based on rapid laboratory diagnosis and modern control methods is desirable for Mediterranean endemic areas.Highlights Contagious agalactia is caused by M. agalactiae and affects small ruminant dairy farms in the Mediterranean basin. Contagious agalactia is endemic in many countries and has a severe health and economic impact. Effect on milk production and composition of mastitis caused by M. agalactiae

Clinical Appropriateness of Coronary Angiography

Background: The study evaluates the appropriateness of coronary angiography and the agreement between the used method and the presence of coronary artery disease by the indications proposed from American College of Cardiology/American Heart Association (1999). Method: The guidelines allow us to associate to Class I and IIa the judgment of appropriateness, to the Class IIb of uncertainty; to Class III of inappropriateness. Result: On 761 coronary angiography 76.74% were appropriate, 23.13% unsuitable, 0.13% uncertain. The group with the greater value of appropriateness is that one with unstable angina (97.9% appropriate); that one with the lower value is the group with non-specific symptomatology (26.7% appropriate). Conclusion: Considering the false positives, it is important the rate of the greater sensibility and the lower specificity of the not invasive tests carried before coronary angiography, as well as, the probable presence of microcircle disease. Among the false negatives, we must considered the number of patients with effective coronary artery disease which has “jumped” the intermediate stage of the not invasive diagnostic process, before the coronary angiography, but have obtained the same final benefit

Genome-Wide Patterns of Homozygosity Reveal the Conservation Status in Five Italian Goat Populations

The application of genomic technologies has facilitated the assessment of genomic inbreeding based on single nucleotide polymorphisms (SNPs). In this study,we computed several runs of homozygosity (ROH) parameters to investigate the patterns of homozygosity using Illumina Goat SNP50 in five Italian local populations: Argentata dell’Etna (N = 48), Derivata di Siria (N = 32), Girgentana (N = 59), Maltese (N = 16) andMessinese (N = 22). The ROH results showed well-defined differences among the populations. A total of 3687 ROH segments >2 Mb were detected in the whole sample. The Argentata dell’Etna and Messinese were the populations with the lowest mean number of ROH and inbreeding coefficient values, which reflect admixture and gene flow. In the Girgentana, we identified an ROH pattern related with recent inbreeding that can endanger the viability of the breed due to reduced population size. The genomes of Derivata di Siria and Maltese breeds showed the presence of long ROH (>16 Mb) that could seriously impact the overall biological fitness of these breeds. Moreover, the results confirmed that ROH parameters are in agreement with the known demography of these populations and highlighted the different selection histories and breeding schemes of these goat populations. In the analysis of ROH islands, we detected harbored genes involved with important traits, such as formilk yield, reproduction, and immune response, and are consistentwith the phenotypic traits of the studied goat populations. Finally, the results of this study can be used for implementing conservation programs for these local populations in order to avoid further loss of genetic diversity and to preserve the production and fitness traits. In view of this, the availability of genomic data is a fundamental resource

Funzione cardiopolmonare in bambini con pregressa infezione da Covid-19 lieve o asintomatica e ritorno all'attività sportiva

Aim - To evaluate the cardiopulmonary function in children returning to play sports after mild or asymptomatic SARS-CoV-2 infection. - Methods - This is a consecutive case series conducted at the Institute for Maternal and Child Health, Trieste, Italy. Paediatric patients who accessed the Institute for cardiologic and pneumological evaluation before the return to play competitive sports were recruited. According to the Italian Sports Medical Federation recommendations, echocardiogram, electrocardiogram, treadmill ECG test and pulmonary function tests were performed. - Results - 240 patients (aged 8-17 years old) were recruited. Among these, 233 children were considered for the final analysis. Out of 233, 147 (63.1%) had a mild symptomatic form of SARS-CoV-2 infection, while 86 (36.9%) were asymptomatic. The main referred symptoms were fever (n = 68, 46.3%), headache (n = 42, 28.6%), anosmia (n = 40, 27.2%), rhinitis (n = 34, 23.1%), ageusia (n = 32, 21.8%), cough (n = 22, 15%), asthenia (n = 21, 14.3%), arthralgia-myalgia (n = 20, 13.6%), sore throat (n = 14, 9.5%) and gastrointestinal symptoms (n = 9, 6.1%). No child presented evidence of cardiopulmonary function impairment after an average time of 76.1 days (SD 39.2) from SARS-CoV-2 swab positivity and a median of 68 days (IQ1 49, IQ3 98). - Conclusion - This study suggests that the diagnostic yield of cardiopulmonary tests before returning to play sports may be very low in the absence of specific symptoms

A high-density genome-wide approach reveals novel genetic markers linked to small ruminant lentivirus susceptibility in sheep

Visna/Maedi virus (VMV) is lentiviral disease of sheep responsible for severe production losses. Multiple genomic regions associated with infection were reported indicating genetic complexity. In this study, a combined genome-wide approach using a high-density SNP array has been performed, comparing VMV-infected (n = 78) and non-infected (n = 66) individuals of the Valle del Belice breed. The serological tests showed a seroprevalence of 26%. The comparison among results from different approaches (GWAS, Fisher’s exact test and the FST analysis) revealed two association signals: on OAR03 close to the GRIN2B gene and on OAR05 close to the TMEM232 gene. To the best of our knowledge, there has been no previous association between these genes and lentiviral infection in any species. The GRIN2B gene plays a role in pain response, synaptic transmission, and receptor clustering, while TMEM232 is involved in the development of immune-related disorders. The results highlighted new aspects of the genetic complexity related to the resistance/susceptibility to VMV in sheep, confirming that studies on different breeds can lead to different results. The ideal approach for validation of the markers identified in our study is to use samples from a population independent from the discovery population with the same phenotype used in the discovery stage