Long-Term effects of physical activity on weight loss, metabolic parameters and blood pressure in subjects undergoing bariatric surgery: A 5-year follow-up study.

BACKGROUND: bariatric surgery stands as an effective intervention for weight loss and improved metabolic control in obesity, although over time there is a proportion of weight regain and type-2-diabetes (T2D) relapse. AIMS: to explore the role of physical activity (PA) after surgery and its impact on metabolic parameters during a 5-year follow-up. METHODS: 148 individuals who underwent bariatric surgery completed scheduled examinations over 5-years. Physical assessments and laboratory tests were conducted pre-surgery and annually thereafter. PA levels were evaluated using the International Physical Activity Questionnaire. RESULTS: participants were split into the PA group, who engaged in regular physical activity, and No-PA group, who remained sedentary throughout. In T2D individuals before surgery, PA group showed significant reductions in blood pressure and a lower T2D recurrence (6.7 â€‹% vs 36 â€‹%) compared to No-PA group. In normoglycemic individuals, the PA group led to sustained BMI reduction and improved blood pressure control (p â€‹< â€‹0.001) compared to No-PA group, for the entire duration of follow-up. CONCLUSIONS: regular PA demonstrated cardio-metabolic benefits post-bariatric surgery. Integrating PA into post-bariatric care could enhance long-term outcomes.

Proposal of a new clinical protocol for evaluating fatigability in adult SMA patients.

Objective: Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease affecting the lower motor neuron, carrying a significant burden on patients' general motor skills and quality of life, characterized by a great variability in phenotypic expression. As new therapeutic options make their appearance on the scene, sensitive clinical tools and outcome measures are needed, especially in adult patients undergoing treatment, in which the expected clinical response is a mild improvement or stabilization of disease progression. Methods: Here, we describe a new functional motor scale specifically designed for evaluating the endurance dimension for the upper and lower limbs in adult SMA patients. Results: The scale was first tested in eight control healthy subjects and then validated in ten adult SMA patients, proving intra- and inter-observer reliability. We also set up an evaluation protocol by using wearable devices including surface EMG and accelerometer. Conclusions: The endurance evaluation should integrate the standard clinical monitoring in the management and follow-up of SMA adult patients.

Making heads or tails of body inversion effects: Do heads matter?

Observers are better at discriminating upright bodies than inverted bodies, and this body inversion effect (BIE) is reliable with whole figures (bodies with heads), but not with bodies presented without heads or the heads occluded suggesting that heads may be key to BIEs. Some studies present whole figures and bodies without heads between groups, and BIEs are not found for bodies without heads [1]. Other studies present whole figures and bodies without heads in the same blocks and BIEs are found with bodies without heads [2]. Does seeing the heads of whole figures induce BIEs in bodies without heads? Here, participants discriminated bodies with either whole figures and bodies without heads presented within blocks, or in separate blocks with bodies without heads presented first. We tested body identity and posture discrimination and measured participants' gaze. BIEs were found with whole figures and bodies without heads in both identity and posture discrimination, and in both study designs. However, efficiency scores were better for the whole figures than the bodies without heads, but only when whole figures appeared in separate blocks. The magnitude of the BIE was overall stronger for whole figures compared to bodies without heads, but only in identity discrimination. BIE magnitudes were similar in the identity and posture tasks. Participants were better at identity discrimination, yet, there was greater looking at heads and less at bodies. During posture discrimination, greater looking at bodies and less at heads was associated with better performance. Faces might influence BIEs but are not essential. Configural representations of bodies without heads are sufficient for BIEs in posture and identity discrimination.

Anthropogenic Drivers Leading to Population Decline and Genetic Preservation of the Eurasian Griffon Vulture (Gyps fulvus).

Human activities are having increasingly devastating effects on the health of marine and terrestrial ecosystems. Studying the adaptive responses of animal species to changes in their habitat can be useful in mitigating this impact. Vultures represent one of the most virtuous examples of adaptation to human-induced environmental changes. Once dependent on wild ungulate populations, these birds have adapted to the epochal change resulting from the birth of agriculture and livestock domestication, maintaining their essential role as ecological scavengers. In this review, we retrace the main splitting events characterising the vultures' evolution, with particular emphasis on the Eurasian griffon Gyps fulvus. We summarise the main ecological and behavioural traits of this species, highlighting its vulnerability to elements introduced into the habitat by humans. We collected the genetic information available to date, underlining their importance for improving the management of this species, as an essential tool to support restocking practices and to protect the genetic integrity of G. fulvus. Finally, we examine the difficulties in implementing a coordination system that allows genetic information to be effectively transferred into management programs. Until a linking network is established between scientific research and management practices, the risk of losing important wildlife resources remains high.

Genetic characterization and implications for conservation of the last autochthonous Mouflon population in Europe.

Population genetic studies provide accurate information on population structure, connectivity, and hybridization. These are key elements to identify units for conservation and define wildlife management strategies aimed to maintain and restore biodiversity. The Mediterranean island of Sardinia hosts one of the last autochthonous mouflon populations, descending from the wild Neolithic ancestor. The first mouflon arrived in Sardinia ~ 7000 years ago and thrived across the island until the twentieth century, when anthropogenic factors led to population fragmentation. We analysed the three main allopatric Sardinian mouflon sub-populations, namely: the native sub-populations of Montes Forest and Mount Tonneri, and the reintroduced sub-population of Mount Lerno. We investigated the spatial genetic structure of the Sardinian mouflon based on the parallel analysis of 14 highly polymorphic microsatellite loci and mitochondrial D-loop sequences. The Montes Forest sub-population was found to harbour the ancestral haplotype in the phylogeny of European mouflon. We detected high levels of relatedness in all the sub-populations and a mitochondrial signature of hybridization between the Mount Lerno sub-population and domestic sheep. Our findings provide useful insights to protect such an invaluable genetic heritage from the risk of genetic depletion by promoting controlled inter-population exchange and drawing informed repopulation plans sourcing from genetically pure mouflon stocks.

Open partial horizontal laryngectomy and adjuvant (chemo)radiotherapy for laryngeal squamous cell carcinoma: results from a multicenter Italian experience.

PURPOSE: To evaluate the functional and oncologic outcomes of adjuvant (chemo)radiation [(C)RT] after open partial horizontal laryngectomies (OPHLs). METHODS: Multicenter retrospective evaluation of 130 patients (116 males, 14 females) submitted between 1995 and 2017 to OPHL Types II and III for laryngeal cancer and receiving adjuvant (C)RT for one or more of the following risk factors at histopathologic examination of the surgical specimen: pT4a and/or > pN2a categories, close/positive resection margins, or presence of both perineural (PNI) and lympho-vascular invasion (LVI). The primary study endpoints were evaluation of the presence of tracheostomy and/or gastrostomy at last follow-up, and calculation of laryngo-esophageal dysfunction-free survival (LEDFS). RESULTS: Mean age of the study cohort was 60.8 ± 8.9 years (median, 62; interquartile range [IQR], 13). Mean follow-up was 50.7 ± 39.4 months (range 24-188; median, 38; IQR, 51). Adjuvant therapy consisted of CRT in 53 (41%) patients, and RT alone in 77 (59%). Five-year LEDFS was 85%. Overall survival was 71.5%, while 13% of patients remained tracheostomy- and 3% gastrostomy-dependent at the last follow-up. The only significant variable in predicting survival (p = 0.020) was tracheostomy dependence: it was maintained in 7.5% of subjects after OPHL Type II and in 34% of those submitted to OHPL Type III (p < 0.001). CONCLUSIONS: In selected patients affected by advanced laryngeal cancer, OPHLs Type II and III have a relatively good laryngeal safety profile and provide favorable oncologic outcomes even in case of need for adjuvant (C)RT.

18-FDG PET for large vessel vasculitis diagnosis and follow-up.

OBJECTIVES: Large vessel vasculitis (LVV) are chronic inflammatory diseases that affect arteries. While a mere clinical-serological approach does not seem sensitive either in the initial evaluation nor in long-term monitoring, 18-FDG positron emission tomography (18-FDG PET) is currently considered a useful assessment tool in LVV. We aimed at exploring the utility of 18-FDG, compared with traditional assessments, in the short- and long-term follow-up of patients with LVV. In addition, we compared patterns of vascular involvement in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA). METHODS: We retrospectively analysed 47 patients affected by LVV, evaluating clinics, blood chemistry and 18-FDG PET results, at two time points, short-term (average 8 months after diagnosis) and long-term (average 29 months). RESULTS: 18-FDG PET uptake, expressed as mean value of SUV max, decreased significantly during follow-up in all the patients. A low concordance between 18-FDG PET and acute phase reactants levels was observed, but also a good sensitivity in detecting the response to treatment. CONCLUSIONS: The results confirm the role of 18-FDG PET as a powerful tool in the evaluation of LVV, both at the time of diagnosis and during monitoring. Furthermore, the data confirm that GCA and TAK are part of the same disease spectrum.

Fingerprinting of anti-alpha enolase antibodies in systemic sclerosis.

OBJECTIVES: Anti-alpha enolase antibodies have been detected in systemic sclerosis (SSc), but little is known on their fine specificity and their predictive value on single disease manifestations. The aim of this work is to perform an epitope mapping of alpha enolase by means of truncated recombinant proteins and to analyse the clinico-serological correlations of anti-alpha enolase antibodies in SSc patients. METHODS: Thirty-eight SSc patients were recruited and fully clinically and serologically characterised. Plasmids encoding full length and truncated polypeptides of alpha enolase were generated; the polypeptides were purified under native conditions and used in dot blot to test sera from SSc patients and controls. The densitometric values obtained on all the polypeptides with anti-IgG subclass specific antibodies were analysed by cluster analysis and partial least square regression. RESULTS: Anti-alpha enolase antibodies (mostly IgG1 and IgG2) are detected in 47% of SSc patients. IgG1 target the amino terminal region of alpha enolase, while IgG2 are more restricted to the central portion of the molecule. Anti-alpha enolase antibodies are not associated with disease-specific antibodies or with interstitial lung disease and do not identify patients affected by the limited vs. diffuse form. CONCLUSIONS: Anti-alpha enolase antibodies are very frequent in SSc but are not associated with clinical or serological features of the disease. Further studies on larger cohorts of patients are necessary to define their possible contribution in defining specific subsets of the disease.

Mitochondrial D-loop Sequence Variability in Three Native Insular Griffon Vulture (Gyps fulvus) Populations from the Mediterranean Basin.

The islands of Sardinia, Crete, and Cyprus are hosting the last native insular griffon populations in the Mediterranean basin. Their states have been evaluated from "vulnerable" to "critically endangered". The sequence analysis of molecular markers, particularly the mtDNA D-loop region, provides useful information in studying the evolution of closely related taxa and the conservation of endangered species. Therefore, a study of D-loop region sequence was carried out to estimate the genetic diversity and phylogenetic relationship within and among these three populations. Among 84 griffon specimens (44 Sardinian, 33 Cretan, and 7 Cypriot), we detected four haplotypes including a novel haplotype (HPT-D) that was exclusively found in the Cretan population with a frequency of 6.1%. When considered as a unique population, haplotype diversity (Hd) and nucleotide diversity (π) were high at 0.474 and 0.00176, respectively. A similar level of Hd and π was found in Sardinian and Cretan populations, both showing three haplotypes. The different haplotype frequencies and exclusivity detected were in accordance with the limited matrilineal gene flow (FST = 0.07097), probably related to the species reluctance to fly over sea masses. The genetic variability we observe today would therefore be the result of an evolutionary process strongly influenced by isolation leading to the appearance of island variants which deserve to be protected. Furthermore, since nesting sites and food availability are essential elements for colony settlement, we may infer that the island's colonization began when the first domestic animals were transferred by humans during the Neolithic. In conclusion, our research presents a first contribution to the genetic characterization of the griffon vulture populations in the Mediterranean islands of Sardinia, Crete and Cyprus and lays the foundation for conservation and restocking programs.

Identification of an ancestral haplotype in the mitochondrial phylogeny of the ovine haplogroup B.

BACKGROUND: European mouflon (Ovis orientalis musimon) has been reintroduced in mainland Europe since the 18th-century sourcing from the Sardinian and Corsican autochthonous mouflon populations. The European mouflon is currently considered the feral descendent of the Asian mouflon (O. orientalis), and the result of first wave of sheep domestication occurred 11,000 years ago in the Fertile Crescent, and brought to Corsica and Sardinia ca. 6,000 years ago, where they still live as autochthonous populations. However, this phylogeny is based on mitogenome sequences of European mouflon individuals exclusively. METHODS: We sequenced the first complete mtDNA of the long-time isolated Sardinian mouflon and compared it with several ovine homologous sequences, including mouflon from mainland Europe and samples representative of the five known mitochondrial domestic sheep haplogroups. We applied Bayesian inference, Maximum Likelihood and Integer Neighbour-Joining network methods and provided a robust, fully-resolved phylogeny with strong statistical support for all nodes. RESULTS: We identified an early split (110,000 years ago) of the Sardinian mouflon haplotype from both sheep and mainland European mouflon belonging to haplogroup B, the latter two sharing a more recent common ancestor (80,000 years ago). Further, the Sardinian mouflon sequence we generated had the largest genetic distance from domestic sheep haplogroups (0.0136 ± 0.004) among mouflon species. Our results suggest the Sardinian mouflon haplotype as the most ancestral in the HPG-B lineage, hence partially redrawing the known phylogeny of the genus Ovis.

Validity and reliability of naturalistic driving scene categorization Judgments from crowdsourcing.

A common challenge with processing naturalistic driving data is that humans may need to categorize great volumes of recorded visual information. By means of the online platform CrowdFlower, we investigated the potential of crowdsourcing to categorize driving scene features (i.e., presence of other road users, straight road segments, etc.) at greater scale than a single person or a small team of researchers would be capable of. In total, 200 workers from 46 different countries participated in 1.5days. Validity and reliability were examined, both with and without embedding researcher generated control questions via the CrowdFlower mechanism known as Gold Test Questions (GTQs). By employing GTQs, we found significantly more valid (accurate) and reliable (consistent) identification of driving scene items from external workers. Specifically, at a small scale CrowdFlower Job of 48 three-second video segments, an accuracy (i.e., relative to the ratings of a confederate researcher) of 91% on items was found with GTQs compared to 78% without. A difference in bias was found, where without GTQs, external workers returned more false positives than with GTQs. At a larger scale CrowdFlower Job making exclusive use of GTQs, 12,862 three-second video segments were released for annotation. Infeasible (and self-defeating) to check the accuracy of each at this scale, a random subset of 1012 categorizations was validated and returned similar levels of accuracy (95%). In the small scale Job, where full video segments were repeated in triplicate, the percentage of unanimous agreement on the items was found significantly more consistent when using GTQs (90%) than without them (65%). Additionally, in the larger scale Job (where a single second of a video segment was overlapped by ratings of three sequentially neighboring segments), a mean unanimity of 94% was obtained with validated-as-correct ratings and 91% with non-validated ratings. Because the video segments overlapped in full for the small scale Job, and in part for the larger scale Job, it should be noted that such reliability reported here may not be directly comparable. Nonetheless, such results are both indicative of high levels of obtained rating reliability. Overall, our results provide compelling evidence for CrowdFlower, via use of GTQs, being able to yield more accurate and consistent crowdsourced categorizations of naturalistic driving scene contents than when used without such a control mechanism. Such annotations in such short periods of time present a potentially powerful resource in driving research and driving automation development.

A Novel -72 (T→A) ß-Promoter Mutation Causing Slightly Elevated HbA2 in a Vietnamese Heterozygote.

We report a novel ß+-thalassemia mutation found in a Vietnamese family. The molecular defect T→A lies at -72 of the ß-globin gene promoter, within the conserved CCAAT box. The index case was a 5-year-old child having red blood cells indices close to normal and slightly increased level of HbA2 (3.96%). The expression of the mutated ß allele was inferred by luciferase reporter assay in K562 cells. The ß -72 determinant is the eighth ß-thalassemic mutation identified in Vietnam and it was not previously reported in any population. The absence of homozygous or compound heterozygous states did not allow us to precisely predict either its clinical impact or its relevance in management programs. Our results further underline the importance of identifying and characterizing new or rare ß+-thalassemic alleles in carrier screening and prenatal diagnosis.

Biochemical and Molecular Analysis of the Hb Lepore Boston Washington in a Syrian Homozygous Child.

Hemoglobin (Hb) Lepore is composed of two normal α chains and two 뫧 fusion globins that arise from unequal crossover events between the δ- and ß-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a ß-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA) assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δß-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.

The New -474(C→T) Substitution Discovered in the HBG2 Promoter of a Sardinian δß-Thalassemia Carrier.

During a screening for hemoglobinopathies, we found a carrier of the Sardinian δß-thalassemia condition. The proband's hematology and hemoglobin (Hb) profile agreed with those of the other carriers previously identified during our diagnostic program except for the fetal Hb (HbF) composition, which consisted of both α2Aγ2 and α2Gγ2 instead of nearly 100% α2Aγ2. In order to explain the unusual γ-chain ratio, sequencing of the Gγ promoter was carried out and revealed two nucleotide substitutions in cis: C→T at position -474 and A→G at position -309 from the Cap site. The latter had previously been observed in subjects with raised HbF levels, although it has not yet been evaluated at functional level. We used the luciferase assay to determine whether the two mutations modify the transcriptional activity of the Gγ promoter. Results indicated that the observed in vivo Gγ-globin production cannot be translated into increased in vitro promoter function, suggesting that the assessed mutations cannot be considered as functional single nucleotide polymorphisms per se; instead, a more complex regulatory mechanism might be involved.

Biorelevant reactions of the potential anti-tumor agent vanadocene dichloride.

The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2VCl2] or VDC) with some relevant bioligands of the cytosol such as proteins (Hb), amino acids (glycine and histidine), NADH derivatives (NADH, NADPH, NAD(+) and NADP(+)), reductants (GSH and ascorbic acid), phosphates (HPO4(2-), P2O7(4-), cAMP, AMP, ADP and ATP) and carboxylate derivatives (lactate) and its uptake by red blood cells were studied. The results indicated that [Cp2VCl2] transforms at physiological pH into [Cp2V(OH)2] and that only HPO4(2-), P2O7(4-), lactate, ATP and ADP form mixed species with the [Cp2V](2+) moiety replacing the two hydroxide ions. EPR and electronic absorption spectroscopy, agarose gel electrophoresis and spin trapping measurements allow excluding any direct interaction and/or intercalation with DNA and the formation of reactive oxygen species (ROS) in Fenton-like reactions. Uptake experiments by erythrocytes suggested that VDC crosses the membrane and enters inside the cells, whereas 'bare' V(IV) transforms into V(IV)O species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC.

Hb F-Avellino [(G)γ41(C7)Phe → Leu; HBG2: c.124 T > C]: A New Hemoglobin Variant Observed In A Healthy Newborn.

Here we describe Hb F-Avellino [(G)γ41(C7)Phe → Leu; HBG2: c.124 T > C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband's hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of the (G)γ gene showed a T to C transition at codon 41 (TTC > CTC) corresponding to the Phe → Leu substitution. Normal functional properties have been hypothesized.

The First Mitogenome of the Cyprus Mouflon (Ovis gmelini ophion): New Insights into the Phylogeny of the Genus Ovis.

Sheep are thought to have been one of the first livestock to be domesticated in the Near East, thus playing an important role in human history. The current whole mitochondrial genome phylogeny for the genus Ovis is based on: the five main domestic haplogroups occurring among sheep (O. aries), along with molecular data from two wild European mouflons, three urials, and one argali. With the aim to shed some further light on the phylogenetic relationship within this genus, the first complete mitochondrial genome sequence of a Cypriot mouflon (O. gmelini ophion) is here reported. Phylogenetic analyses were performed using a dataset of whole Ovis mitogenomes as well as D-loop sequences. The concatenated sequence of 28 mitochondrial genes of one Cypriot mouflon, and the D-loop sequence of three Cypriot mouflons were compared to sequences obtained from samples representatives of the five domestic sheep haplogroups along with samples of the extant wild and feral sheep. The sample included also individuals from the Mediterranean islands of Sardinia and Corsica hosting remnants of the first wave of domestication that likely went then back to feral life. The divergence time between branches in the phylogenetic tree has been calculated using seven different calibration points by means of Bayesian and Maximum Likelihood inferences. Results suggest that urial (O. vignei) and argali (O. ammon) diverged from domestic sheep about 0.89 and 1.11 million years ago (MYA), respectively; and dates the earliest radiation of domestic sheep common ancestor at around 0.3 MYA. Additionally, our data suggest that the rise of the modern sheep haplogroups happened in the span of time between six and 32 thousand years ago (KYA). A close phylogenetic relationship between the Cypriot and the Anatolian mouflon carrying the X haplotype was detected. The genetic distance between this group and the other ovine haplogroups supports the hypothesis that it may be a new haplogroup never described before. Furthermore, the updated phylogenetic tree presented in this study determines a finer classification of ovine species and may help to classify more accurately new mitogenomes within the established haplogroups so far identified.

A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or α91(FG3)Leu→Ile (α2) (HBA2: c.274C > A).

We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1ß2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus.

A new unstable variant of the fetal hemoglobin HBG2 gene: Hb F-Turritana [(G) γ64(E8)Gly→Asp, HBG2:c.194G>A] found in cis to the Hb F-Sardinia gene [(A) γ(E19)Ile→Thr, HBG1:c.227T>C].

A new variant of the fetal hemoglobin (Hb) was observed in a newborn baby subjected to phototherapy due to jaundice, by means of electrophoretic and chromatographic techniques. The variant Hb resulted unstable by the isopropanol stability test. After HBG2 gene sequencing, the G to A transversion at codon 64, position eight of the E helix, was found, which corresponds to the Asp for Gly amino acid substitution. The new variant was called Hb F-Turritana [(G) γ64(E8)Gly→Asp, HBG2:c.194G>A]. Incoming aspartic acid residue, bulky and negatively charged, may be responsible for alteration of the heme pocket steric configuration and for instability. The new abnormal HBG2 gene was found to be associated in cis with the mutated HBG1 gene, which characterizes the Hb F-Sardinia [(A) γ (E19)Ile→Thr, HBG1:c.227T>C] variant.

Photovoltaic properties of PSi impregnated with eumelanin.

A bulk heterojunction of porous silicon and eumelanin, where the columnar pores of porous silicon are filled with eumelanin, is proposed as a new organic-inorganic hybrid material for photovoltaic applications. The addition of eumelanin, whose absorption in the near infrared region is significantly higher than porous silicon, should greatly enhance the light absorption capabilities of the empty porous silicon matrix, which are very low in the low energy side of the visible spectral range (from about 600 nm downwards). The experimental results show that indeed the photocarrier collection efficiency at longer wavelengths in eumelanin-impregnated samples is clearly higher with respect to empty porous silicon matrices.