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The dog was probably the first domesticated animal. Despite extensive archaeological and genetic investigations, the origin and the evolution of the extant dogs are still being debated. Dog breeds that have over time been selected for hunting share common ancestral traits. This study represents the first comprehensive attempt to survey at the genomic and mitochondrial level eight hound-like dogs breeds indigenous to the Mediterranean Basin to determine if they share common ancient origins. Results from the microsatellite analysis indicate that all the dog populations have a low inbreeding value.The Kelb tal-Fenek has a high divergence from the current Egyptian street population, however there is not enough evidence from this study to exclude completely the potential of an ancient common relationship. Overall, the mitochondrial results indicate high frequencies of haplogroups A and B and a low representation of haplogroup C, while only one Egyptian dog could be assigned to haplogroup D. Results reveal identities and shared clades, suggesting the conservation of ancient European mitotypes in the Mediterranean hound-like breeds, especially in the Egyptian population. Although none of the dog populations/breeds participating in this study indicate to be direct descendants of the Egyptian dogs, they still have a very close morphologically resemblance to those iconic Egyptian dogs often depicted in ancient art forms and share some genetic links with the current Egyptian population. Further research is required with other markers such us complete mitogenomes and SNP panels to confirm the complex history of the Mediterranean dogs involved in this study.

The identification of the dwarf phenotype in chicken is based on body weight, height, and shank length, leaving the differentiation between dwarf and small breeds ambiguous. The aims of the present study were to characterize the sequence variations associated with the dwarf phenotype in three Italian chicken breeds and to investigate the genes associated with their phenotype. Five hundred and forty-one chickens from 23 local breeds (from 20 to 24 animals per breed) were sampled. All animals were genotyped with the 600 K chicken SNP array. Three breeds were described as “dwarf”, namely, Mericanel della Brianza (MERI), Mugellese (MUG), and Pepoi (PPP). We compared MERI, MUG, and PPP with the four heaviest breeds in the dataset by performing genome-wide association studies. Results showed significant SNPs associated with dwarfism in the MERI and MUG breeds, which shared a candidate genomic region on chromosome 1. Due to this similarity, MERI and MUG were analyzed together as a meta-population, observing significant SNPs in the LEMD3 and HMGA2 genes, which were previously reported as being responsible for dwarfism in different species. In conclusion, MERI and MUG breeds seem to share a genetic basis of dwarfism, which differentiates them from the small PPP breed.

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Background: Randomized controlled trials (RCTs) proved that short-term (21–90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. Methods: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. Results: We evaluated 1070 patients, who had 72 (interquartile range, 62–79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score 24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. Conclusions: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05476081.

Increases in chicken production are mainly due to specialised breeds. However, local breeds are of increasing importance, known for ability to adapt to the environment and unique products. Conventional poultry products contain lower levels of n-3 fatty acids (FAs) compared to those obtained from local breeds, therefore the aim of this study was to evaluate the modulation of expression of genes involved in long-chain polyunsaturated FA (PUFA) biosynthesis pathways according to genetic background, diet conditions, and sex. Animals from two local breeds and a commercial line were fed different diets: control and experimental diet (10% linseed supplementation). For each breed and diet group, both sexes were reared. The RNA was extracted from 36 liver samples and sequenced by RNAseq method. Bioinformatic analysis was carried out to find differentially expressed genes from comparisons between experimental groups. Results showed low impact of diet on differentially expressed genes related to FA biosynthesis, but linseed diet increased percentage of n-3 FAs of liver. Sex and genetic background determined the differential expression of genes related to long-chain PUFA biosynthesis. Specifically, females of local breeds shared 23 up-regulated genes when compared to their respective commercial line groups. Some of the shared genes had a role in de novo triglyceride biosynthesis (MTTPL and GPAM), and in de novo FA biosynthesis (ACACA and SCD) was detected. In conclusion, local breeds are able to better adapt to a diet rich in PUFA, by triggering certain transcriptomic shifts in the liver that allow birds to process the high PUFA content provided by diet.

Background: Randomized-controlled trials (RCTs) reported a finding on the safety and efficacy of percutaneous patent foramen ovale (PFO) closure to prevent stroke recurrence. It showed that the Amplatzer (AMP) device appears to be superior to medical therapy (MT) in preventing strokes and episodes of atrial fibrillation (AF), than other devices. We performed a network meta-analysis (NMA) to evaluate the closure of PFO in preventing subsequent neurological events while investigating the results obtained by specific devices. Methods: We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) and identified 6 RCTs until March 2019. We performed an NMA and used pooled ORs. Analyses were done in NetMetaXL1.6-WinBUGS1.4. Results: Six RCTs with 3,560 patients (mean age 45.2–46.2 years) were included in the present NMA. Depending on the device, 4 groups of patients were compared with MT: 1,889 patients undergoing PFO closure were significantly less likely to experience a stroke than 1,671 patients treated with MT (ORs 0.41; 95% Cr.I. 0.27–0.60 with fixed-effects model and ORs 0.22; 95% Cr.I. 0.05–0.70 with random-effects model). The patients with AMP showed a similar risk than those treated with Helex/Cardioform (HLX/CF) or with a group of 11 multiple devices. This suggests the equality between the 2 most currently used devices. When assessing TIA and, for the safety analysis, major bleeding, both models confirm no significant difference between any devices and MT. PFO closure increased the risk of new-onset AF: MT induces AF significantly less than all the devices. In favor of the AMP, there is a reduced number of cases of AF versus MT; however, no device superiority has been established in comparing HLX/CF and other devices in a random effect model. Conclusions: Our NMA provides evidence in favor of PFO closure with all the devices currently in use. We can conclude that these devices are better than MT, but not that 1 device is better than the rest in reducing stroke recurrences and AF episodes in the follow-up.

The purpose of this study was to investigate the effects of high levels of Tenebrio molitor dietary inclusion (15%) on molecular mechanisms that influence poultry health in a broiler chicken diet. The global gene expression of four tissues (breast, liver, jejunum, and caecum) was evaluated using the RNA-Seq approach. The analysis of differentially expressed genes suggested that the use of Tenebrio molitor leads to the overexpression of genes related to protein elongation required for tissue growth and development in the gut and liver. It would also appear to contain nutrients that reduce the expression of genes related to the immune system and inflammation of the mucosa. The dietary inclusion of Tenebrio molitor in poultry could also lead to a possible inactivation of the growth factor and a reduction of tissue free-radicals. No genes alterations have been detected in liver RNA expression that would discourage the use of larvae in feeding broilers.

It is not known whether the current territorial organization for acute revascularization treatments in ischemic stroke patients guarantees similar time to treatment and functional outcomes among different levels of institutional stroke care. We aimed to assess the impact of time to treatment on functional outcomes in ischemic stroke patients who received intravenous thrombolysis (IVT) alone, bridging (IVT plus thrombectomy), or primary thrombectomy in level 1 and level 2 Stroke Units (SUs) in Triveneto, a geographical macroarea in Northeast of Italy. We conducted an analysis of data prospectively collected from 512 consecutive ischemic stroke patients who received IVT and/or mechanical thrombectomy in 25 SUs from September 17th to December 9th 2018. The favorable outcome measures were mRS score 0–1 and 0–2 at 3months. The unfavorable outcome measures were mRS score 3–5 and death at 3months. We estimated separately the possible association of each variable for time to treatment (onset-to-door, door-to-needle, onset-to-needle, door-to-groin puncture, needle-to-groin puncture, and onset-to-groin puncture) with 3-month outcome measures by calculating the odds ratios (ORs) with two-sided 95% confidence intervals (CI) after adjustment for pre-defined variables and variables with a probability value ≤ 0.10 in the univariate analysis for each outcome measure. Distribution of acute revascularization treatments was different between level 1 and level 2 SUs (p < 0.001). Among 182 patients admitted to level 1 SUs (n = 16), treatments were IVT alone in 164 (90.1%), bridging in 12 (6.6%), and primary thrombectomy in 6 (3.3%) patients. Among 330 patients admitted to level 2 SUs (n = 9), treatments were IVT alone in 219 (66.4%), bridging in 74 (22.4%), and primary thrombectomy in 37 (11.2%) patients. Rates of excellent outcome (51.4% vs 45.9%), favorable outcome (60.1% vs 58.7%), unfavorable outcome (33.3% vs 33.8%), and death (9.8% vs 11.3%) at 3months were similar between level 1 and 2 SUs. No significant association was found between time to IVT alone (onset-to-door, door-to-needle, and onset-to-needle) and functional outcomes. After adjustment, door-to-needle time ≤ 60min (OR 4.005, 95% CI 1.232–13.016), shorter door-to-groin time (OR 0.991, 95% CI 0.983–0.999), shorter needle-to-groin time (OR 0.986, 95% CI 0.975–0.997), and shorter onset-to-groin time (OR 0.994, 95% CI 0.988–1.000) were associated with mRS 0–1. Shorter door-to-groin time (OR 0.991, 95% CI 0.984–0.998), door-to-groin time ≤ 90min (OR 12.146, 95% CI 2.193–67.280), shorter needle-to-groin time (OR 0.983, 95% CI 0.972–0.995), and shorter onset-to-groin time (OR 0.993, 95% CI 0.987–0.999) were associated with mRS 0–2. Longer door-to-groin time (OR 1.007, 95% CI 1.001–1.014) and longer needle-to-groin time (OR 1.019, 95% CI 1.005–1.034) were associated with mRS 3–5, while door-to-groin time ≤ 90min (OR 0.229, 95% CI 0.065–0.808) was inversely associated with mRS 3–5. Longer onset-to-needle time (OR 1.025, 95% CI 1.002–1.048) was associated with death. Times to treatment influenced the 3-month outcomes in patients treated with thrombectomy (bridging or primary). A revision of the current territorial organization for acute stroke treatments in Triveneto is needed to reduce transfer time and to increase the proportion of patients transferred from a level 1 SU to a level 2 SU to perform thrombectomy.

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.

In Iran, approximately 70 % of goats are bred for meat and wool. Markhoz goat is one of the most important goat breeds reared in Kurdistan and Kermanshah regions for Angora - mohair production. Previous research has introduced several QTLs affecting mohair traits in Angora goats; this study aimed to confirm QTLs controlling mohair traits on chromosomes 1, 2, 5, 13, 19, and 24. For this purpose, eight bucks with an average of 32 offspring were taken into consideration. The studied traits included fleece weight, average fiber diameter, staple length, and fine, medullated, kemp fiber percentage. Thirty microsatellite markers on chromosomes 1, 2, 5, 13, 19, and 24 were used for genotyping. Microsatellite markers were selected according to previous studies and goat genetic map, based on their distance on the chromosome. The least-squares regression method was used to locate QTLs. Five QTLs significant affecting mohair traits: two of them related to mohair weight traits; one QTL was significant for fiber features and quality, in particular for fiber diameter, staple length and kemp fiber. Two of them are reported for the first time in chromosomes 1 and 2 for kemp fiber and fleece weight traits respectively.

Objective Systematic reviews suggest that patent foramen ovale closure (PFOc) is performed percutaneously with low complication rates. We did a network meta-analysis (NMA) comparing devices for PFO closures, evaluating safety and efficacy of transcatheter PFOc in preventing neurological events in patients with stroke when compared with medical therapy (MT), and assessing risk of atrial fibrillation (AF). Methods We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) identifying six randomized controlled trials from 2012 until December 2019. We performed a Bayesian NMA; number-needed-to-treat and number-needed-to-harm were derived by applying the estimated odds ratios (ORs). The likelihood of being helped or harmed (LHH) was evaluated to estimate the risk-effectiveness balance. Results The 3560 patients allocated to PFOc were less subject to a stroke than patients with MT. The overall ORs of PFOc versus MT were 0.41 with fixed-effects, and 0.22 with random-effects model. NMA proves that PFOc induces AF episodes significantly higher than MT, even when analysis is limited to only new episodes of “serious AF.” LHH (0.68 fixed-effects, 0.79 random-effects) showed that strokes saved are less than cases of AFs added. By considering only serious AF, strokes saved are higher than serious AFs induced by the PFOc (LHH was 3.46 and 4.00 respectively). Conclusions NMA supported PFOc in patients with cryptogenic stroke, confirming that devices are better than MT, but increase the risk of AF by over 2/4 times (serious or unserious AF). Considering serious AFs (real risky clinical condition), patients have more advantages in being treated, since LHH is ≥ 3–4.

BACKGROUND Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied. METHODS We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding. RESULTS A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001). CONCLUSIONS Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

Climate change has the potential to adversely affect the health of livestock, with consequences to animal welfare, greenhouse gas emissions, productivity, human health and livelihoods. Phenotypic plasticity is the ability of a genotype to produce different phenotypes, depending on environmental, biotic or abiotic conditions; it is a factor influencing and modifying the genes of animal and plant organisms, to adaptation to climate change. Among the various climate variables, heat stress has been reported to be the most detrimental factor to the economy of the livestock industry. There are a number of candidate genes that are associated with adaptation of ruminants, monogastric and poultry to heat stress. For instance, the genes encoding leptin, thyroid hormone receptor, insulin growth factor-1, growth hormone receptor, are associated with the impacts of heat stress on the physiological pathways of domestic animals such as dairy cows, beef cattle, buffaloes, poultry, pigs and horses. This review aims to highlight genes and traits that are involved with thermo-tolerance of domestic animals to sustain production and to cope with climate change. Selection and experimental evolution approaches have shown that plasticity is a trait that can evolve when under direct selection and has a correlated response to some specific traits. Therefore, new breeding goals should be defined for the potential of livestock species to acquire plasticity for adaptation to the current climate changing conditions.Highlights Heat stress compromises feed intake, growth, milk and meat quality and quantity, resulting in a significant financial burden to global livestock. Genetic selection and nutritional intervention are key strategies to consider in Animal Genetic Resources in hot environments. Information from gene expression or genome-wide association studies can be used to further improve the accuracy of selection.

Submitted 2020-07-02 | Accepted 2020-09-03 | Available 2020-12-01 https://doi.org/10.15414/afz.2020.23.mi-fpap.137-143 According to census accomplished in 2001, only 9% of Italian poultry breeds are still widespread. This project aims to describe morphological variability and genetic background among 13 Italian autochthonous chicken breeds, 10 from Northern Italy and 3 from Central Italy. An updated biometrical measurement protocol was established starting from phenotypic characterization guidelines released by FAO. Six traits were registered on each animal: live body weight (LBW), body length (BL), shank length (SL), shank width (SW), breast width (BW), and wingspan (WS). Moreover, all breeds were genotyped using the Affymetrix 600 K Chicken SNP Array, in order to evaluate genetic variability and population structure. Means of BL and BW showed low variability among breeds, with the lowest value in Pepoi (BL = 32.29 ± 1.57 cm and BW = 28.92 ± 1.93 cm), and maximum in Robusta Lionata for BL (46.79 ± 1.66 cm) and in Robusta Maculata for BW (42.33 ± 3.60 cm). On the contrary, average LBW varied notably among breeds, with the highest value for Robusta Maculata (♂ 4,221.7 ± 450.6 g; ♀ 2,831.7 ± 253.2 g) and the lowest values for Modenese males (1,695.0 ± 128.1 g) and Pepoi females (1,293.3 ± 219.2 g). The lowest observed heterozygosity (Ho) and expected heterozygosity (He) were obtained for Padovana Argentata (Ho: 0.151 ± 0.198; He: 0.146 ± 0.185) and the highest for Millefiori di Lonigo (Ho: 0.293 ± 0.199; He: 0.291 ± 0.178). Furthermore, multidimensional scaling plot showed clear genetic identity for each breed, with clusters formed according to geographical and historical origin of the breeds, which were confirmed in neighbor networks. 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Simple Summary New genomic tools have been used as an instrument in order to assess the molecular pathway involved in heat stress resistance. Local chicken breeds have a better attitude to face heat stress. This review aims to summarize studies linked to chickens, heat stress, and heat shock protein. Abstract Chicken products are the most consumed animal-sourced foods at a global level across greatly diverse cultures, traditions, and religions. The consumption of chicken meat has increased rapidly in the past few decades and chicken meat is the main animal protein source in developing countries. Heat stress is one of the environmental factors which decreases the productive performance of poultry and meat quality. Heat stress produces the over-expression of heat shock factors and heat shock proteins in chicken tissues. Heat shock proteins regulate several molecular pathways in cells in response to stress conditions, changing the homeostasis of cells and tissues. These changes can affect the physiology of the tissue and hence the production ability of chickens. Indeed, commercial chicken strains can reach a high production level, but their body metabolism, being comparatively accelerated, has poor thermoregulation. In contrast, native backyard chickens are more adapted to the environments in which they live, with a robustness that allows them to survive and reproduce constantly. In the past few years, new molecular tools have been developed, such as RNA-Seq, Single Nucleotide Polymorphisms (SNPs), and bioinformatics approaches such as Genome-Wide Association Study (GWAS). Based on these genetic tools, many studies have detected the main pathways involved in cellular response mechanisms. In this context, it is necessary to clarify all the genetic and molecular mechanisms involved in heat stress response. Hence, this paper aims to review the ability of the new generation of genetic tools to clarify the molecular pathways associated with heat stress in chickens, offering new perspectives for the use of these findings in the animal breeding field.

Introduction Although pathogenesis of small vessel disease is poorly understood, increasing evidence suggests that endothelial dysfunction may have a relevant role in development and progression of small vessel disease. In this cross-sectional study, we investigated the associations between imaging signs of small vessel disease and blood biomarkers of endothelial dysfunction at two different time points in a population of ischaemic stroke patients. Patients and methods In stroke patients treated with intravenous thrombolysis, we analysed blood levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and vascular endothelial growth factor. Three reviewers independently assessed small vessel disease features using computed tomography. At baseline and 90 days after the index stroke, we tested the associations between single and combined small vessel disease features and levels of blood biomarkers using linear regression analysis adjusting for age, sex, hypertension, diabetes, smoke. Results A total of 263 patients were available for the analysis. Mean age (±SD) was 69 (±13) years, 154 (59%) patients were male. We did not find any relation between small vessel disease and endothelial dysfunction at baseline. At 90 days, leukoaraiosis was independently associated with intercellular adhesion molecule-1 (β = 0.21; p = 0.016) and vascular cell adhesion molecule-1 (β = 0.22; p = 0.009), and lacunes were associated with vascular endothelial growth factor levels (β = 0.21; p = 0.009) whereas global small vessel disease burden was associated with vascular endothelial growth factor (β = 0.26; p = 0.006). Discussion Leukoaraiosis and lacunes were associated with endothelial dysfunction, which could play a key role in pathogenesis of small vessel disease. Conclusions Small vessel disease features and total burden were associated with endothelial dysfunction 90 days after the stroke, whereas there was no relation during the acute phase. Our results suggest that endothelial dysfunction, particularly vascular endothelial growth factor, is involved in pathological process of small vessel disease.

Whale watching is a dynamic industry and, in particular in a country like Iceland, where tourism is currently playing a leading role in the national economy and where nature – understood in a broad sense – represents the main attraction for visitors, whale watching, rapidly grown during the last years, shows an evident potential under an ecotouristic point of view. In recent times, an increasing need for the understanding of interactions between humans (tourists) and wildlife (whales) emerged, highlighting the interest towards environmental conservation, protection and preservation matters and towards the search for activities, and modalities, that could essentially contribute to the sustainability of tourism experiences, such as wildlife tourism ones. It is difficult to argue with the fact that whale watching uses the whale “asset” in a non-destructive way, unlike whaling, activity still commercially conducted in Iceland, but at the same time it can’t be considered ecotouristic and sustainable a priori. In fact, several studies point out how tourism has a disturbing effect on wildlife and negatively affects their ecology and short- to long-term behaviours. This article, after a general introduction on the main ecotourism principles, examines the whale watching industry of the “Whale Capital of Iceland”, Húsavík, and it mainly focuses on the results and data of two researches conducted in the field – respectively among whale watchers and among the local whale watching companies. The purpose of this work is to investigate if and how Húsavík whale watching is following an environmentally sustainable and ecotouristic path, and to bring into light its strengths and weaknesses as a whale watching destination., Almatourism - Journal of Tourism, Culture and Territorial Development, Vol 7, No 14 (2016)

Objective To describe the role of biochemical anomalies of tyrosine (TYR), tryptophan (TRP), and arginine (ARG) metabolism in patients suffering from episodic and chronic cluster headache (CCH). Background The pathogenesis of cluster headache (CH) and the process that transforms the episodic into the chronic form are unknown. However, the accompanying symptoms suggest a dysfunction of the sympathetic system and hypothalamus along with anomalies of metabolism of catecholamines, elusive amines, and nitric oxide (NO) metabolism. Methods We describe the results obtained from the last papers published on this issue. The level of metabolites were analyzed by different high-performance liquid chromatography methods. Results In both episodic and CH patients, the levels of dopamine and elusive amines are very elevated. The only biochemical difference found in studies between episodic and chronic cluster was that norepinephrine levels were significantly lower in episodic cluster in comparison to control and chronic subjects. In addition, the levels of ARG, homoarginine, and citrulline, precursors of synthesis of NO, were significantly lower in chronic cluster. Conclusions All these results suggest that TYR, TRP, and ARG metabolism is abnormal and may constitute a biochemical fingerprint of CH patients. The increased levels of norepinephrine in chronic cluster constitute a possible cause of chronicity of this primary headache. The high levels of tryptamine and its activity on the central serotoninergic system may explain why the length of CH is brief in comparison to migraine and tension-type headache. The low levels of ARG, homoarginine, and citrulline may be the consequence of high circulating levels of α1 -agonists, such as epinephrine and norepinephrine, and their biochemical interaction with endothelial trace amine-associated receptor 1 that induces activation of NO synthase, resulting in NO synthesis in the circulation, NO release, intense vasodilation, and as a result, the cluster attack.

Small vessel disease (SVD) is frequent in aging and stroke patients. Inflammation and remodeling of extracellular matrix have been suggested as concurrent mechanisms of SVD. We investigated the relationship between imaging features of SVD and circulating metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with ischaemic stroke. In patients treated with intravenous thrombolysis, we took blood samples before intravenous thrombolysis and 90 days after the acute stroke and analysed levels of MMPs and TIMPs. We assessed leukoaraiosis, number of lacunes and brain atrophy on pre-treatment CT scan and graded global SVD burden combining such features. We investigated associations between single features, global SVD and MMPs and TIMPs at baseline and at follow-up, retaining univariate statistically significant associations in multivariate linear regression analysis and adjusting for clinical confounders. A total of 255 patients [mean (±SD) = 68.6 (± 12.7) years, 154 (59%) males] were included, 107 (42%) had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. A total of 107 (42%) patients had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. After adjustment, only TIMP-4 proved associations with SVD features. Brain atrophy was associated with baseline TIMP-4 (β = 0.20;p = 0.019) and leukoaraiosis with 90 days TIMP-4 (β = 0.19; p = 0.013). Global SVD score was not associated with baseline TIMP-4 levels (β = 0.10; p = 0.072), whereas was associated with 90 days TIMP-4 levels (β = 0.21; p = 0.003). Total SVD burden was associated with higher TIMP-4 levels 90 days after stroke, whereas was not during the acute phase. Our results support a biological relationship between SVD grade and TIMP-4.

Background Since its approval, the use of alteplase had been limited to patients aged ≤80 years. Aims TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. Methods TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0–2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. Results Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69–2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. Conclusions The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Intravenous thrombolysis (IVT) is the treatment of choice for most patients with acute ischemic stroke. According to the recently updated guidelines, IVT should be administered in absence of absolute exclusion criteria. We aimed to assess the proportion of ischemic strokes potentially eligible and actually treated with IVT, and to explore the reasons for not administering IVT. We prospectively collected and analyzed data from 1184 consecutive ischemic stroke patients admitted to the 22 Stroke Units (SUs) of the Veneto region from September 18th to December 10th 2017. Patients were treated with IVT according to the current Italian guidelines. For untreated patients, the reasons for not administering IVT were reported by each center in a predefined model including absolute and/or relative exclusion criteria and other possible reasons. Out of 841 (71%) patients who presented within 4.5 h of stroke onset, 704 (59%) had no other absolute exclusion criteria and were therefore potentially eligible for IVT according to the current guidelines. However, only 323 (27%) patients were eventually treated with IVT. Among 861 (73%) untreated patients, 480 had at least one absolute exclusion criterion, 283 only relative exclusion criteria, 56 only other reasons, and 42 a combination of relative exclusion criteria and other reasons. Our study showed that only 46% (323/704) of the potentially eligible patients were actually treated with IVT in the SUs of the Veneto region. All healthcare professionals involved in the acute stroke pathway should make an effort to bridge this gap between eligibility and reality.

Background Dimethyl fumarate (DMF) is approved as first line therapy for relapsing-remitting multiple sclerosis (RRMS). In some (3%) patients, DMF induces a marked lymphopenia. Herpes simplex encephalitis (HSE) may occur in lymphopenic subjects under treatment with immune-suppressive drugs. Case presentation We report a case of a 39-year-old female patient with RRMS that developed HSE temporally associated with a marked and sudden drop in lymphocyte count, from 1200/µl to 600/µl, in the peripheral blood. HSE DNA was demonstrated in the cerebrospinal fluid. HSE had the features that characterize HSE occurring in immunosuppressed subjects, i.e. less prominent CSF pleocytosis, bilateral and mainly cortical involvement and less extensive tissue necrosis. Antiviral therapy determined a progressive, although incomplete, improvement. Three months later the patient presented only a mild short-term memory deficit and sporadic episodes of inappropriate emotionality. Lymphocyte count returned to normal values (1120/µl) after DMF discontinuation. Conclusion Our case of HSE in a lymphopenic DMF-treated RRMS patient, points out the necessity of further studies on DMF-related lymphopenia, especially whether it implies an impaired immunity against viruses.

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell’Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19–7.53); SAP:5.46 (1.64–18.74); Δmetalloproteinase 9:1.60 (1.12–2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

Background and Purpose— Significance and management of blood pressure (BP) changes in acute stroke care are unclear. Here, we aimed to investigate the impact of 24-hour BP variability (BPV) on outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. Methods— From the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis registry, 28 976 patients with documented pre-treatment systolic BP at 2 and 24 hours were analyzed. The primary measure of BP variability was successive variability. Data were preprocessed using coarsened exact matching. We assessed early neurological improvement, symptomatic intracerebral hemorrhage (SICH), and long-term functional outcome (modified Rankin Scale [mRS] at 90 days) by binary and ordinal regression analyses. Results— Attempts to explain successive variation for analysis of BPV with patients characteristics at admission found systolic BP (5.5% variance) to be most influential, yet 92% of BPV variance remained unexplained. Independently from systolic BP, successive variation for analysis of BPV was associated with poor functional outcome mRS score of 0 to 2 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90–0.98), disadvantage across the shift of mRS (OR, 1.04; 95% CI, 1.01–1.08), mortality (OR, 1.10; 95% CI, 1.01–1.08), SICH SITS (OR, 1.14; 95% CI, 1.06–1.23), and SICH ECASS (OR, 1.24; 95% CI, 1.10–1.40; ECASS [European Cooperative Acute Stroke Study 2]). Analyzing successive variation for analysis of BPV as a function of pre-treatment, systolic BP significantly improved the prediction of functional outcome (mRS score of 0–1, mRS score of 0–2, neurological improvement, mRS-shift: all P interaction Conclusions— This study suggests the need for a more individual BP management accounting for pre-treatment BP and the acute BP course (ie, BPV) to achieve best possible outcome for the patient.

Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals. Methods Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants. Results The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals. Conclusions These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.

The primary aim of this study (TA-CH, Tryptophan Amine in Chronic Headache) was to investigate a possible role of tryptophan (TRP) metabolism in chronic migraine (CM) and chronic tension-type headache (CTTH). It is not known if TRP metabolism plays any role in CM and/or CTTH. Plasma levels of serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), metabolite of 5-HT, and tryptamine (TRY) were tested in 73 patients with CM, 15 patients with CTTH and 37 control subjects. Of these, plasmatic TRY was significantly lower in CM (p < 0.001) and in CTTH (p < 0.002) patients with respect to control subjects, while 5-HIAA levels in plasma were within the same range in all groups. 5-HT was undetectable in the plasma of almost all subjects. Our results support the hypothesis that TRP metabolism is altered in CM and CTTH patients, leading to a reduction in plasma TRY. As TRY modulates the function of pain matrix serotonergic system, this may affect modulation of incoming nociceptive inputs from the trigeminal endings and posterior horns of the spinal cord. We suggest that these biochemical abnormalities play a role in the chronicity of CM and CTTH.

Objective: The pathogenesis of chronic migraine (CM) remains largely unknown. We hypothesized that anomalies of tyrosine metabolism, found in migraine without aura (MwwA) patients, play an important role in the transformation of MwwA into CM, since the increase in the number of MwwA attacks is the most predisposing factor for the occurrence of CM. Methods: To test our hypothesis we measured the plasma levels of dopamine (DA), noradrenaline (NE) and trace amines, including tyramine (TYR) and octopamine (OCT), in a group of 73 patients with CM, 13 patients with chronic tension-type headache (CTTH) and 37 controls followed in the Headache Centers of the Neurology Departments of Asti, Milan and Vicenza hospitals in Italy. Results: The plasma levels of DA and NE were several-fold higher in CM patients compared with control subjects ( p > 0.001). The plasma levels of TYR were also extremely elevated ( p > 0.001); furthermore, these levels progressively increased with the duration of the CM. Conclusions: Our data support the hypothesis that altered tyrosine metabolism plays an important role in the pathogenesis of CM. The high plasma levels of TYR, a potent agonist of the trace amine associated receptors type 1 (TAAR1), may ultimately down-regulate this receptor because of loss of inhibitory presynaptic regulation, therein resulting in uncontrolled neurotransmitter release. This may produce functional metabolic consequences in the synaptic clefts of the pain matrix implicated in CM.

Premesse La riduzione del rischio di recidive di ischemia cerebrale con la terapia antitrombotica e del 20% circa. Il fallimento clinico e stato imputato a resistenza ai farmaci antiaggreganti. I dati in letteratura sono molto variabili a causa dell’eterogeneita delle casistiche cliniche studiate e dei metodi di laboratorio utilizzati.

Influenza vaccination has been implicated in Guillain Barre Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.

Background Experimentally, metalloproteinases (MMPs) play a detrimental role related to the severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA-treated stroke patients. Methods Blood was taken before and 24-h after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as confluent petechiae within the infarcted area or any parenchymal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes Results Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17–2.38], p = 0.005; 1.74 [1.21–2.49], p = 0.003, respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17–2.57], p = 0.006) with a trend toward significance for MMP9/TIMP2 ratio (p = 0.007). Discussion Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA-treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect.