60 research outputs found
Profiling Cognitive and Social Functioning in a Small Cohort with Malan Syndrome
No full textBackground/Objectives: Malan syndrome (MALNS) is an ultra-rare genetic disorder caused by aberrations in the NFIX gene, located at chromosome 19p13.2. Key features of MALNS include general overgrowth, a typical facial gestalt, muscle–skeletal abnormalities, speech difficulties and intellectual disability. Additionally, MALNS frequently presents with autism-like behaviour and social challenges. However, characterisation of the cognitive profile of MALNS, including social perception skills, is limited. Methods: Six children and adolescents with MALNS, whose clinical and emotional–behavioural features had been described in previous studies, were assessed by means of a single, co-normed neuropsychological battery covering multiple cognitive domains. Results: Consistent with their intellectual disability, performance was generally weak across all neuropsychological subtests. Nonetheless, memory for faces, visual attention and contextual (non-verbal) theory of mind emerged as relative strengths of the profile, both at group and individual levels. Conversely, tasks requiring verbal reasoning and language comprehension, such as comprehension of instructions and verbal theory of mind, represented weaknesses for all participants. Conclusions: These findings provide a further characterisation of cognitive and social functioning in MALNS, which can inform future research as well as clinical practice and rehabilitatio
The Target Therapy Hyperbole: “KRAS (p.G12C)”—The Simplification of a Complex Biological Problem
No full textKirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene variations are linked to the development of numerous cancers, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). The lack of typical drug-binding sites has long hampered the discovery of therapeutic drugs targeting KRAS. Since “CodeBreaK 100” demonstrated Sotorasib’s early safety and efficacy and led to its approval, especially in the treatment of non-small cell lung cancer (NSCLC), the subsequent identification of specific inhibitors for the p.G12C mutation has offered hope. However, the CodeBreaK 200 study found no significant difference in overall survival (OS) between patients treated with Docetaxel and Sotorasib (AMG 510), adding another degree of complexity to this ongoing challenge. The current study compares the three-dimensional structures of the two major KRAS isoforms, KRAS4A and KRAS4B. It also investigates the probable structural changes caused by the three major mutations (p.G12C, p.G12D, and p.G12V) within Sotorasib’s pocket domain. The computational analysis demonstrates that the wild-type and mutant isoforms have distinct aggregation propensities, resulting in the creation of alternate oligomeric configurations. This study highlights the increased complexity of the biological issue of using KRAS as a therapeutic target. The present study stresses the need for a better understanding of the structural dynamics of KRAS and its mutations to design more effective therapeutic approaches. It also emphasizes the potential of computational approaches to shed light on the complicated molecular pathways that drive KRAS-mediated oncogenesis. This study adds to the ongoing efforts to address the therapeutic hurdles presented by KRAS in cancer treatment
Ear Nose Throat Manifestations In Hypoidrotic Ectodermal Dysplasia
No full textThe ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form
Sonographic and molecular diagnosis of thanatophoric dysplasia type I at 18 weeks of gestation
No full textStatus assessment of the Critically Endangered Azores Bullfinch Pyrrhula murina
No full text'This work was part of the Azores Bullfinch monitoring programme included in the project LIFE NAT/P/000013 “Recovery of Azores Bullfinch’s habitat in the Special Protection Area of Pico da Vara / Ribeira do Guilherme”'The Azores Bullfinch is endemic to the island of São Miguel (Azores, Portugal). Its status was uplisted to Critically Endangered in 2005 on the basis of an extremely small and declining population that was considered to be restricted to a very small mountain range (43 km2), in a single location, within which the spread of invasive plants constituted a threat to habitat quality. Nevertheless, information was mostly inferred, or the product of, non-systematic studies. In order to carry out a complete assessment of the conservation status we analysed: (i) population trend, calculated from annual monitoring 1991–2008, (ii) population size, and (iii) range size, obtaining estimates in a single morning study in 2008 involving the simultaneous participation of 48 observers. Contrary to previous inferences, the population is no longer decreasing, although quality of laurel forest habitat continues to decline due to the persistent threat of invasive species. Population size (mean ± SE) was estimated at 1,064 ± 304 individuals using distance sampling methods, although the estimate was very sensitive to the survey method used. Range size estimates (extent of occurrence and area of occupancy) were 144 km2 and 83 km2 respectively. Given the present information, we propose the downlisting of Azores Bullfinch to Endangered on the IUCN Red List.Peer reviewe
Molecular Pathway-Based Classification of Ectodermal Dysplasias: First Five-Yearly Update
No full textTo keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we searched the databases PubMed and OMIM for the term “ectodermal dysplasia”, referring mainly to changes in the last 5 years. We also tried to obtain information about those diseases on which the last scientific report appeared more than 15 years ago by contacting the authors of the most recent publication. A group of experts, composed of researchers who attended the 8th International Conference on Ectodermal Dysplasias and additional members of the previous classification panel, reviewed the proposed amendments and agreed on a final table listing all 49 currently known ectodermal dysplasias for which the molecular genetic basis has been clarified, including 15 new entities. A newly reported ectodermal dysplasia, linked to the gene LRP6, is described here in more detail. These ectodermal dysplasias, in the strict sense, should be distinguished from syndromes with features of ectodermal dysplasia that are related to genes extraneous to the currently known pathways involved in ectodermal development. The latter group consists of 34 syndromes which had been placed on the previous list of ectodermal dysplasias, but most if not all of them could actually be classified elsewhere. This update should streamline the classification of ectodermal dysplasias, provide guidance to the correct diagnosis of rare disease entities, and facilitate the identification of individuals who could benefit from novel treatment options
Influenza A (H1N1)-induced ischemic stroke in a child: case report and review of the literature
No full textIschemic stroke is an important cause of death and long term morbidity in children. Viral respiratory infections are emerging
as important risk factors responsible for ischemic stroke in this age group. The direct action of virus against cerebral vessels,
autoimmune reactivity, and increased production of cytokines are advocated as the main factors for causing ischemic stroke.
This study can be useful for clarifying some molecular aspects of H1N1 virus infection in children.
We report on the case of a H1N1-induced ischemic stroke in a Caucasian 2 year-old female. The cerebrospinal fluid samples
showed the positivity of polymerase chain reaction for influenza A (H1N1) infection, confirmed also by pharyngeal swab
culture. Increased levels of cerebrospinal fluid interleukin 6 and interleukin 1β were also detected.
H1N1 virus infection has been identified as an important cause of neurological involvement in children. The findings of
increased levels of Interleukin 6 and interleukin 1β in the cerebrospinal fluid of this child with H1N1 induced-ischemic stroke
seems to validate the role of pro-inflammatory cytokines as crucial mediators of cerebral thrombus formation
Ectodermal dysplasias: An overview and update of clinical and molecular‐functional mechanisms
No full textAnalysis of the influence of biomechanical and anthropometrical factors on the performance of golf swing
No full textLAUREA MAGISTRALELo swing del golf è un gesto che implica la generazione di movimento e forze da parte di tutto il sistema corporeo del golfista.
Un’analisi del gesto di swing deve essere caratterizzata da un duplice approccio:
- analisi della biomeccanica del movimento del golfista
- analisi delle caratteristiche antropometriche del golfista
Considerando entrambi questi aspetti, si può ottenere una valutazione completa e valida della performance del giocatore di golf. Questo studio si propone come obiettivo l’analisi di tutti i parametri coinvolti nell’elaborazione del gesto di swing e della loro influenza sulla realizzazione del movimento, in modo da fornire al golfista uno strumento utile per migliorare performance e tecnica.
Il presente lavoro è stato effettuato in collaborazione tra il Laboratorio di Analisi della Postura e del Movimento “Luigi Divieti” del Politecnico di Milano e l’Instituto de Biomecánica de Valencia, dell’Universidad Politécnica de Valencia.
Come soggetti di studio, sono stati analizzati dieci giocatori semi-professionali appartenenti alla Escuela de Alto Rendimiento de la Federación Valenciana, di età compresa tra i 17 e i 23 anni, con un range di handicap tra -1.7 e 5.
In primis è stata realizzata un’analisi antropometrica dei golfisti: attraverso l’utilizzo di uno Scanner 3D sono state rilevate tutte le grandezze relative alle dimensioni e le altezze di tutti i principali segmenti corporei. Diametri ossei, perimetri muscolari e spessore della pliche corporea sono invece stati rilevati con strumentazione supplementare quale segmometro, metro e plicometro. Da queste misure sono stati poi ottenuti i somatotipi dei soggetti, seguendo il sistema di misura di ISAK basato sul metodo di Heath-Carter.
In secondo luogo, si è sviluppata un’analisi biomeccanica dei giocatori attraverso un sistema di fotogrammetria costituito da dieci telecamere con frequenza di acquisizione pari a 250 Hz associato a due piattaforme dinamometriche. Per ogni giocatore, sono state acquisite cinque misure del gesto di swing effettuato con un driver appositamente progettato in base alle caratteristiche antropometriche dei giocatori. Dalla suddetta analisi, tramite la realizzazione di un modello biomeccanico per l’implementazione dei dati, sono state rilevate numerose variabili cinematiche e cinetiche: gli angoli assunti dalle diverse articolazioni durante il movimento di swing, le velocità angolari dei segmenti corporei, i momenti articolari, le forze di reazione al terreno e i relativi momenti, i tempi di realizzazione del gesto e infine gli spostamenti del centro di pressione. Per una migliore analisi del gesto di swing, questo è stato diviso in sette fasi differenti, per ognuna delle quali sono state rilevate tutte le variabili biomeccaniche corrispondenti.
Una volta acquisiti ed elaborati tutti i parametri antropometrici e biomeccanici, i dati sono stati analizzati tramite uno studio statistico. La valutazione statistica si è effettuata da una parte con l’analisi descrittiva dei dati, e dall’altra con l’analisi delle correlazioni esistenti tra parametri antropometrici, biomeccanici, e di rendimento. Come fattori di rendimento sono stati scelti:
1. velocità della testa della mazza
2. angolo orizzontale di lancio della palla
3. handicap del golfista
I fattori che consentono di valutare la performance di un tiro in una partita di golf sono la distanza raggiunta dalla palla e la sua direzione. Pertanto, la velocità della testa della mazza così come l’angolo di lancio della palla, essendo fortemente correlati con queste due grandezze, sono stati considerati come parametri di rendimento. L’handicap invece, essendo un indicatore della bravura del golfista relazionato con la sua capacità di mettere in buca la palla nel minor numero di colpi, è stato assunto come parametro di misura dell’abilità del golfista. Per la correlazione statistica, sono state considerate significative le relazioni aventi un coefficiente di correlazione di Pearson ≥ 0.45 e un p-value < 0.001.
I risultati ottenuti hanno dimostrato che:
- I parametri di rendimento sono significativamente influenzati dal rango di movimento dei segmenti corporei del golfista nell’atto di esecuzione dello swing. In particolare, è stato notato come diversi tipi di allenamenti influenzino effettivamente i parametri biomeccanici, e quindi la loro correlazione con gli indicatori di performance.
- Le caratteristiche fisiche del soggetto influenzano effettivamente la sua capacità di generare forza nel lancio, condizione rilevabile attraverso la valutazione della velocità della testa della mazza. Soggetti con somatotipi diversi, e in particolare piu mesomorfi, hanno infatti dimostrato di ottenere una maggiore velocità di lancio, legata alla maggiore muscolatura del giocatore.
- Somatotipi diversi, infine, hanno dimostrato differenze nel movimento di esecuzione dello swing: i soggetti più ectomorfi risultano avere un rango di movimento della parte alta del corpo che sfrutta l’altezza, mentre i più endomorfi sembrano avere un maggior movimento di pelvis e tronco dovuto alla minore muscolatura. I parametri biomeccanici, inoltre, risultano essere significativamente influenzati da massa e altezza del golfista.
Il presente lavoro, quindi, dimostra l’importanza dell’analisi sia antropometrica che biomeccanica nello studio del gesto del swing nel golf, e costituisce uno studio preliminare alla determinazione di un gesto “ottimale” di swing che possa essere considerato da golfisti e allenatori come un utile strumento di valutazione della performance nel golf.Golf is a very demanding physical game and the golf “swing” is a complex movement that involves the whole body.
An analysis of the gesture of swing must be characterized by a double approach:
- analysis of the biomechanics of golfer’s movement
- analysis of the anthropometric characteristics of the golfer
Considering both these aspects, it can be obtained a complete and valid assessment of the golfer’s performance. This study aims to analyse all the parameters involved in the swing gesture and investigate their influence on the realization of the movement, in order to provide the golfer with an useful tool to improve performance and technique.
The present study was developed in cooperation between the Laboratory of Postural and Motion Analysis “Luigi Divieti” of Politecnico of Milan and the Biomechanical Institute of Valencia (IBV) of Universidad Politécnica of Valencia.
In this study, 10 semi-professional golf players of the school of high performance of the Federación Valenciana were analyzed, aged between 17 and 23 years, with a range of handicap among -1.7 and 5, all of them right-handed.
First of all, an anthropometric analysis of the golfers has been realized: through the use of a Scanner 3D all the principal dimensions and heights of body segments have been detected. Osseous diameters, muscular perimeters and thickness of skin folds have been measured with additional instruments: segmometer, plicometer and tape measure. The measurements made with this complementary instrumentation provided additional information for the characterization of the somatotype, which was obtained following the ISAK procedure.
In addition, it has been developed a biomechanical analysis of players through a photogrammetric system consisting of ten cameras with a sample frequency of 250 Hz associated with two dynamometric platforms. For each player, five measures of the movement of swing were carried out with a driver specifically planned according to the anthropometric characteristics of the golfer. From this analysis, through the realization of a biomechanical model for the implementation of the data, numerous variables kinematic and kinetic have been detected: angles described by the various joints during movement of swing, angular velocities of the body segments, articular torques, ground reaction forces and relative moments, times of the main swing phases and finally center of pressure displacements. In this study, the swing movement has been divided in seven essential parts, for each of them all corresponding biomechanical variables have been detected.
Once acquired and processed all anthropometric and biomechanical variables, the data were analyzed by a statistical study. The statistical assessment consisted on the one hand in a descriptive analysis of the data and on the other hand in the analysis of the correlations between anthropometric, biomechanical, and performance parameters. As performance factors have been chosen:
1. Club head speed
2. Horizontal angle of delivering the ball
3. Golfer’s handicap
Factors influencing the performance evaluation of a golf shot are the distance attained by the ball and its direction. Therefore, the club head speed as well as the launch angle have been considered as performing factors, being strongly correlated with these quantities. Handicap instead, is a well known numerical measure of a golfer's ability, related to hitting balls into a series of holes on a course using the fewest number of strokes. For the statistical correlation were considered significant relationships with a Pearson correlation coefficient ≥ 0.45 and a p-value <0.001.
The results have shown that:
- Performance parameters are significantly influenced by the movement of specific body segments detected during the golf swing. Then it could be deduced that training aimed at timing and specifical movements of those segments might have a noticeable influence on performance.
- Physiological capacities may improve the ability of golfers to execute stronger shots during swing, which translates in higher club head velocity. Subjects with different somatotypes produce different club head speed, in particular those with a higher amount of mesomorphy, characterized by bigger muscles, demonstrated better skill in accelerating the club head.
- Different executions of the swing motion are associated to different somatotypes: more ectomorph subjects have demonstrated to use their height for extending the range of motion of the higher part of the body, while those being characterized by a higher level of endomorphy seam to emphasize the movement of pelvis and trunk. Furthermore, biomechanical parameters are strongly influenced by the golfer's body mass and height.
This thesis shows therefore the importance of carrying out a biomechanical as well an anthropometrical analysis of the swing movement in golf, with the objective of defining its execution. It can be considered as a preliminary study for the definition of an “optimal” swing, furnishing a useful means for golfers and coachers to evaluate many aspects of training and performance in golf
The Right to Ask, the Need to Answer—When Patients Meet Research: How to Cope with Time
No full textReaching a diagnosis and its communication are two of the most meaningful events in the physician–patient relationship. When facing a disease, most of the patients’ expectations rely on the hope that their clinicians would be able to understand the cause of their illness and eventually end it. Rare diseases are a peculiar subset of conditions in which the search for a diagnosis might reveal a long and painful journey scattered by doubts and requiring, in most cases, a long waiting time. For many individuals affected by a rare disease, turning to research might represent their last chance to obtain an answer to their questions. Time is the worst enemy, threatening to disrupt the fragile balance among affected individuals, their referring physicians, and researchers. It is consuming at all levels, draining economic, emotional, and social resources, and triggering unpredictable reactions in each stakeholder group. Managing waiting time is one of the most burdensome tasks for all the parties playing a role in the search for a diagnosis: the patients and their referring physicians urge to obtain a diagnosis in order to know the condition they are dealing with and establish proper management, respectively. On the other hand, researchers need to be objective and scientifically act to give a rigorous answer to their demands. While moving towards the same goal, patients, clinicians, and researchers might have different expectations and perceive the same waiting time as differently hard or tolerable. The lack of information on mutual needs and the absence of effective communication among the parties are the most common mechanisms of the failure of the therapeutic alliance that risk compromising the common goal of a proper diagnosis. In the landscape of modern medicine that goes faster and claims high standards of cure, rare diseases represent an exception where physicians and researchers should learn to cope with time in order to care for patients
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