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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.
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Arteritis de Células Gigantes , Arteritis de Takayasu , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Arteritis de Células Gigantes/diagnóstico por imagen , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Radiofármacos , Estudios Retrospectivos , Arteritis de Takayasu/diagnóstico por imagenRESUMEN
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.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Anciano , Carcinoma de Células Escamosas/patología , Quimioradioterapia , Quimioradioterapia Adyuvante , Femenino , Humanos , Italia/epidemiología , Neoplasias Laríngeas/cirugía , Laringectomía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Resultado del TratamientoRESUMEN
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.
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Fosfopiruvato Hidratasa , Esclerodermia Sistémica , Autoanticuerpos , Mapeo Epitopo , Humanos , Inmunoglobulina GRESUMEN
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: CâT at position -474 and AâG 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.
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Hemoglobina Fetal/genética , Regulación de la Expresión Génica/genética , Región de Control de Posición/genética , Mutación Puntual , Regiones Promotoras Genéticas/genética , Talasemia beta/genética , Talasemia delta/genética , Adulto , Femenino , Hemoglobina Fetal/biosíntesis , Humanos , Italia , Masculino , Talasemia beta/sangre , Talasemia delta/sangreRESUMEN
Here we describe Hb F-Avellino [(G)γ41(C7)Phe â 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 â Leu substitution. Normal functional properties have been hypothesized.
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Hemoglobina Fetal/genética , Mutación Puntual , gamma-Globinas/genética , Sustitución de Aminoácidos , Codón , Variación Genética , Humanos , Recién NacidoRESUMEN
We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)LeuâIle (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.
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Hemoglobina A2/genética , Hemoglobinas Anormales/genética , Mutación , Adulto , Alelos , Sustitución de Aminoácidos , Heterocigoto , Humanos , Masculino , Globinas alfa/genética , Talasemia alfa/diagnóstico , Talasemia alfa/genéticaRESUMEN
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)GlyâAsp, 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)IleâThr, HBG1:c.227T>C] variant.
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Hemoglobina Fetal/genética , Variación Genética , Hemoglobinas Anormales/genética , Alelos , Sustitución de Aminoácidos , Codón , Hemoglobina Fetal/metabolismo , Hemoglobinas Anormales/metabolismo , Heterocigoto , Humanos , Recién Nacido , Talasemia beta/diagnóstico , Talasemia beta/genética , gamma-Globinas/genética , gamma-Globinas/metabolismoRESUMEN
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< â0.001) 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.
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Cirugía Bariátrica , Presión Sanguínea , Ejercicio Físico , Pérdida de Peso , Humanos , Femenino , Masculino , Cirugía Bariátrica/métodos , Pérdida de Peso/fisiología , Estudios de Seguimiento , Persona de Mediana Edad , Adulto , Ejercicio Físico/fisiología , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/cirugía , Obesidad Mórbida/cirugía , Resultado del TratamientoRESUMEN
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.
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Atrofia Muscular Espinal , Calidad de Vida , Adulto , Humanos , Reproducibilidad de los Resultados , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Fatiga , Protocolos ClínicosRESUMEN
BACKGROUND: HbF-Monserrato-Sassari is a newly discovered abnormal fetal hemoglobin observed in an apparently normal newborn baby during a hemoglobinopathies survey at birth in North Sardinian population. METHODS: Electrophoretic analysis of the cord blood lysate evidenced for an abnormal tetramer due to a mutated fetal globin chain. Electrospray ionisation-mass spectrometry and gene sequencing were used to identify the mutation. Oxygen binding ability of the variant Hb was determined. RESULTS: Sequencing of the γ globin genes revealed the TGTâCGT transition at codon 93 in one of the two (G)γ genes, which leads to the Arg for Cys amino acid replacement at position 9 of the F α-helix. The amino acid substitution was confirmed by mass spectrometric analysis of the globin chains. Since modifications or substitutions at position ß93 are known to affect the arrangement of a salt bridge at the α1ß2 sliding contacts that are crucial for subunit cooperativity, the functional properties of the variant were studied to evaluate the effect of the replacement at the same position in the γ globin chain. With respect to normal HbF, the variant showed a significant increase in oxygen affinity and a slight decrease of both Bohr effect and cooperativity. GENERAL SIGNIFICANCE: Result indicates a key role of the Cys γ93 residue for subunit cooperativity in the TâR transition of the HbF tetramer. Substitutions at the F9 position of the (G)γ globin may result in stabilization of the high affinity R-state of the Hb tetramer. Because of the loss of Cys γ93 residue, this variant is considered to be potentially compromised in nitric oxide transport.
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Hemoglobina Fetal/fisiología , Arginina/química , Cromatografía Líquida de Alta Presión , Cisteína/química , Hemoglobina Fetal/química , Hemoglobina Fetal/genética , Humanos , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
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.
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Discriminación en Psicología/fisiología , Cuerpo Humano , Orientación/fisiología , Reconocimiento Visual de Modelos/fisiología , Postura , Percepción Visual/fisiología , Adolescente , Adulto , Femenino , Cabeza , Humanos , Masculino , Estimulación Luminosa , Tiempo de Reacción , Adulto JovenRESUMEN
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.
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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.
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Conservación de los Recursos Naturales , Oveja Doméstica/genética , Animales , Animales Salvajes , Conservación de los Recursos Naturales/métodos , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , Demografía , Europa (Continente)/epidemiología , Variación Genética , Haplotipos , Italia/epidemiología , Repeticiones de Microsatélite/genética , Filogenia , Vigilancia de la Población , Ovinos/clasificación , Ovinos/genética , Oveja Doméstica/clasificaciónRESUMEN
Two healthy newborns, heterozygous for two different gamma-globin chain mutations, were observed during an electrophoretic screening for hemoglobinopathies in Sassari, North Sardinia (Italy). The variants were characterized by reversed phase high performance liquid chromatography (HPLC) and sequencing of amplified gamma-globin genes. One of the two abnormalities was a novel (A)gammachain variant and the tetramer was named Hb F-Osilo [(A)gamma119(GH2)Gly-->Ser]. The other was a (G)gamma chain variant, Hb F-Paulinia [(G)gamma80(EF4)Asp-->Tyr], already described in a Brazilian baby of African ancestry. No functional studies could be performed.
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Hemoglobina Fetal/genética , Hemoglobinas Anormales/genética , gamma-Globinas/genética , Brasil , Análisis Mutacional de ADN , Hemoglobinopatías/diagnóstico , Humanos , Recién Nacido , Italia , MutaciónRESUMEN
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.
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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.
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Aves/genética , Conservación de los Recursos Naturales , Variación Genética/genética , Mitocondrias/genética , Animales , ADN Mitocondrial/genética , Especies en Peligro de Extinción , Genética de Población , Haplotipos/genética , Humanos , FilogeniaRESUMEN
In this report we describe the complete sequence of the mtDNA genome of Ammotragus lervia (Barbary sheep or aoudad) as obtained by PCR and sequencing with primer walking using flanking sequences. The molecule is 16,530 base pairs in length, resulting similar to those of goat and sheep. The genome organization matches to those of other mammalian mitochondrial genomes. The phylogenetic position of the Ammotragus relative to twelve other mammalian species was assessed based on protein-coding sequences. A goat-aoudad split of 9.9-8.9 MYBP has been estimated, whereas the divergence ancestor/caprines was dated at 12.1-10.8 MYBP.
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ADN Mitocondrial/genética , Genoma Mitocondrial/genética , Rumiantes/genética , Animales , Secuencia de Bases , Datos de Secuencia Molecular , Homología de Secuencia de AminoácidoRESUMEN
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.
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Conducción de Automóvil , Consenso , Colaboración de las Masas/métodos , Ambiente , Clasificación , Femenino , Humanos , Juicio , Reproducibilidad de los ResultadosRESUMEN
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.
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Hemoglobinas Anormales , Homocigoto , Talasemia beta , Niño , Hemoglobinas Anormales/química , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/metabolismo , Humanos , Siria , Talasemia beta/genética , Talasemia beta/metabolismoRESUMEN
We report a novel ß+-thalassemia mutation found in a Vietnamese family. The molecular defect TâA 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.