Vascular function and cardiovascular risk factors in women with severe flushing

Background: Seventy per cent of postmenopausal women suffer from hot flushes causing significant morbidity in 25%. Oestrogen replacement provides symptom relief, but its use has declined following safety issues and there is, as yet, no good alternative. Pathophysiology is poorly understood, but one proposed mechanism is altered peripheral vascular reactivity. It has recently been suggested that the presence of flushing may be a marker of underlying cardiovascular risk. <p/>Aim: To measure (i) peripheral vascular reactivity in subcutaneous vessels (ii) routine and novel cardiovascular risk factors in postmenopausal women who flush, and compare results to a matched group of women who do not flush. <p/>Methods: Thirty-two postmenopausal women with at least 20 flushes/week and 14 nonflushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging, and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine [Ach] (endothelial-dependent) and sodium nitroprusside [SNP] (endothelial independent). Blood samples for risk factors were taken following vascular assessment. <p/>Results: Both study groups were well matched demographically. The response of the subcutaneous vessels was greater in women who flushed than those who did not, following administration of both the endothelium-dependent and independent vasodilators, (ACh, P ≤ 0·001, SNP, P = 0·001, 2-way anova). By contrast, levels of High Density Lipoprotein (HDL)-cholesterol and ApoA1 were significantly lower in the flushing women compared with the control women (P = 0·02 and 0·002, respectively), and levels of inter-cellular adhesion molecule-1 (ICAM-1) were higher (P = 0·03), findings robust to adjustment for confounders, suggesting an adverse cardiovascular risk profile. <p/>Conclusion: These results confirm a better vascular response in women but paradoxically, such women appear to have worse (not better) cardiovascular disease risk factors in particular lower HDL-cholesterol but also higher non-HDL-c to HDL-c ratio and increased ICAM-1. Further studies are needed to assess vascular risk factors in women who flush

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to soy isoflavones and maintenance of bone mineral density (ID 1655) and reduction of vasomotor symptoms associated with menopause (ID 1654, 1704, 2140, 3093, 3154, 3590) (further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

<p>Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a scientific opinion on health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to soy isoflavones and maintenance of bone mineral density and reduction of vasomotor symptoms associated with menopause. The food constituent that is the subject of the claim, soy isoflavones, is sufficiently characterised. The claimed effects, maintenance of bone mineral density and reduction of vasomotor symptoms associated with menopause, which are eligible for further assessment, are beneficial physiological effects. The proposed target populations are peri- and/or post-menopausal women. On the basis of the data presented, the Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of soy isoflavones and maintenance of bone mineral density, and between the consumption of soy isoflavones and reduction of vasomotor symptoms associated with menopause.</p&gt

Independent impacts of aging on mitochondrial DNA quantity and quality in humans

Background The accumulation of mitochondrial DNA (mtDNA) mutations, and the reduction of mtDNA copy number, both disrupt mitochondrial energetics, and may contribute to aging and age-associated phenotypes. However, there are few genetic and epidemiological studies on the spectra of blood mtDNA heteroplasmies, and the distribution of mtDNA copy numbers in different age groups and their impact on age-related phenotypes. In this work, we used whole-genome sequencing data of isolated peripheral blood mononuclear cells (PBMCs) from the UK10K project to investigate in parallel mtDNA heteroplasmy and copy number in 1511 women, between 17 and 85 years old, recruited in the TwinsUK cohorts. Results We report a high prevalence of pathogenic mtDNA heteroplasmies in this population. We also find an increase in mtDNA heteroplasmies with age (β = 0.011, P = 5.77e-6), and showed that, on average, individuals aged 70-years or older had 58.5% more mtDNA heteroplasmies than those under 40-years old. Conversely, mtDNA copy number decreased by an average of 0.4 copies per year (β = −0.395, P = 0.0097). Multiple regression analyses also showed that age had independent effects on mtDNA copy number decrease and heteroplasmy accumulation. Finally, mtDNA copy number was positively associated with serum bicarbonate level (P = 4.46e-5), and inversely correlated with white blood cell count (P = 0.0006). Moreover, the aggregated heteroplasmy load was associated with blood apolipoprotein B level (P = 1.33e-5), linking the accumulation of mtDNA mutations to age-related physiological markers. Conclusions Our population-based study indicates that both mtDNA quality and quantity are influenced by age. An open question for the future is whether interventions that would contribute to maintain optimal mtDNA copy number and prevent the expansion of heteroplasmy could promote healthy aging

Patellofemoral pain syndrome (PFPS): a systematic review of anatomy and potential risk factors

Patellofemoral Pain Syndrome (PFPS), a common cause of anterior knee pain, is successfully treated in over 2/3 of patients through rehabilitation protocols designed to reduce pain and return function to the individual. Applying preventive medicine strategies, the majority of cases of PFPS may be avoided if a pre-diagnosis can be made by clinician or certified athletic trainer testing the current researched potential risk factors during a Preparticipation Screening Evaluation (PPSE). We provide a detailed and comprehensive review of the soft tissue, arterial system, and innervation to the patellofemoral joint in order to supply the clinician with the knowledge required to assess the anatomy and make recommendations to patients identified as potentially at risk. The purpose of this article is to review knee anatomy and the literature regarding potential risk factors associated with patellofemoral pain syndrome and prehabilitation strategies. A comprehensive review of knee anatomy will present the relationships of arterial collateralization, innervations, and soft tissue alignment to the possible multifactoral mechanism involved in PFPS, while attempting to advocate future use of different treatments aimed at non-soft tissue causes of PFPS

Origin and insertion of the medial patellofemoral ligament: a systematic review of anatomy.

PURPOSE: The medial patellofemoral ligament (MPFL) is the major medial soft-tissue stabiliser of the patella, originating from the medial femoral condyle and inserting onto the medial patella. The exact position reported in the literature varies. Understanding the true anatomical origin and insertion of the MPFL is critical to successful reconstruction. The purpose of this systematic review was to determine these locations. METHODS: A systematic search of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed and Cochrane Library) and unpublished literature databases was conducted from their inception to the 3 February 2016. All papers investigating the anatomy of the MPFL were eligible. Methodological quality was assessed using a modified CASP tool. A narrative analysis approach was adopted to synthesise the findings. RESULTS: After screening and review of 2045 papers, a total of 67 studies investigating the relevant anatomy were included. From this, the origin appears to be from an area rather than (as previously reported) a single point on the medial femoral condyle. The weighted average length was 56 mm with an 'hourglass' shape, fanning out at both ligament ends. CONCLUSION: The MPFL is an hourglass-shaped structure running from a triangular space between the adductor tubercle, medial femoral epicondyle and gastrocnemius tubercle and inserts onto the superomedial aspect of the patella. Awareness of anatomy is critical for assessment, anatomical repair and successful surgical patellar stabilisation. LEVEL OF EVIDENCE: Systematic review of anatomical dissections and imaging studies, Level IV

Αυτοματοποιημένος εντοπισμός και διάγνωση μασητικών τερηδόνων (ICDAS II) με αλγόριθμους από ψηφιακές εικόνες ενδοστοματικής κάμερας in vivo

Εισαγωγή Πολυάριθμες τεχνικές έχουν αναπτυχθεί για την αξιολόγηση της τερηδονικής κατάστασης των μασητικών επιφανειών ως συμπληρωματική βοήθεια στην άμεση οπτική παρατήρηση. Σκοπό έχουν να ελαχιστοποιήσουν τη διακύμανση στις αποφάσεις μεταξύ διαφορετικών κλινικών αλλά και από τον ίδιο κλινικό σε διαφορετικές χρονικές στιγμές. Σκοπός Σκοπός αυτής της μελέτης είναι να εφαρμοστεί και να αξιολογηθεί η αξιοπιστία ενός αυτοματοποιημένου συστήματος διάγνωσης μασητικών τερηδονικών βλαβών σε ψηφιακές φωτογραφίες που έχουν ληφθεί από δόντια in vivo με τη χρήση ενδοστοματικής κάμερας. Μεθοδολογία Ο εξεταστής εκπαιδεύτηκε σε θεωρητικό και πρακτικό επίπεδο με τα εργαλεία τυποποίησης του συστήματος ICDAS IIκαι τυποποιήθηκε με το «χρυσό εξεταστή» αξιολογώντας δόντια ενδοστοματικά και από φωτογραφίες στην οθόνη του υπολογιστή. Τα ευρήματά τους συγκρίθηκαν μέχρι να φτάσουν σε συμφωνία 98% (>85%). Το δείγμα αποτέλεσαν 106 μόνιμοι γομφίοι ασθενών που βρίσκονταν υπό θεραπεία στη Μεταπτυχιακή κλινική Παιδοδοντιατρικής και στην Προπτυχιακή κλινική Οδοντικής Χειρουργικής της Οδοντιατρικής Σχολής ΕΚΠΑ. Δόντια με αναπτυξιακές διαταραχές της αδαμαντίνης ή της οδοντίνης αποκλείστηκαν από τη μελέτη. Οι μασητικές επιφάνειες των γομφίων ήταν ελεύθερες τερηδόνας ή είχαν τερηδονικές βλάβες που ανήκαν στις κατηγορίες 1 έως 6 του συστήματος ICDAS II. Τα δόντια εξετάστηκαν και φωτογραφήθηκαν in vivo μέσα στο στόμα των ασθενών. Πριν από την εξέταση και φωτογράφηση, τα δόντια καθαρίζονταν από οργανικά υπολείμματα και χρωστικές με τρίχινο βουρτσάκι σε χειρολαβή χαμηλών ταχυτήτων και ξεπλένονταν με spray νερού-αέρα για 10 δευτερόλεπτα. Έπειτα στεγνώνονταν με αέρα για 5 δευτερόλεπτα. Η φωτογράφηση γινόταν με την ενδοστοματική κάμερα Carestream – CS 1200.Στη συνέχεια ο εξεταστής αξιολογούσε τις μασητικές επιφάνειες in vivo–άμεση οπτική παρατήρηση- και αφού ταξινομούσε κάθε περιοχή ενδιαφέροντος κατά ICDAS II, σημείωνε το περίγραμμα και τον κωδικό της κάθε βλάβης σε μία εκτυπωμένη εικόνα που είχε ληφθεί από την κάμερα. Ο εξεταστής επαναξιολογούσε τα ίδια δόντια 15 μέρες αργότερα από τις ψηφιακές εικόνες στην οθόνη του υπολογιστή με τον ίδιο τρόπο –έμμεση οπτική παρατήρηση-.Για την καταγραφή των αποτελεσμάτων από την άμεση και έμμεση οπτική παρατήρηση χρησιμοποιήθηκε μια εφαρμογή με Superpixels που αναπτύχθηκε σε περιβάλλον Java. 86 από αυτές τις φωτογραφίες (συνολικά 3024 Superpixels) χρησιμοποιήθηκαν για την εκπαίδευση του αλγόριθμου. Ύστερα 20 διαφορετικές φωτογραφίες που περιείχαν πολλαπλές περιοχές ενδιαφέροντος αξιολογήθηκαν από τον αλγόριθμο και τα αποτελέσματα συγκρίθηκαν με αυτά από την άμεση και έμμεση οπτική παρατήρηση. Στατιστική ανάλυση Τα δεδομένα επεξεργάστηκαν και αναλύθηκαν με το πρόγραμμα STATA 12. Η ταξινόμηση του εξεταστή (από την άμεση και έμμεση οπτική παρατήρηση) συγκρίθηκαν με την ταξινόμηση του αλγορίθμου. Υπολογίστηκαν η συνολική συμφωνία (σταθμισμένη και απόλυτη) καθώς και ο σταθμισμένος συντελεστής k. Αποτελέσματα Συγκρίνοντας την ταξινόμηση του συστήματος με την ταξινόμηση του εξεταστή από την άμεση οπτική παρατήρηση στο στόμα βρέθηκαν τιμές ευαισθησίας από 29,2% έως 100% (μ.ο. 59.1%), ειδικότητας από 52,4% έως 99,2% (μ.ο. 91,3%), ορθότητας από 11,1% έως 95,4% (μ.ο. 49,9%) ανάμεσα στις διάφορες κατηγορίες και η ακρίβεια του συστήματος 74%. Ο σταθμισμένος συντελεστής kυπολογίστηκε στο 0,701 ενώ η τιμή για το μη σταθμισμένο συντελεστή k βρέθηκε να είναι 0,587. Συγκρίνοντας την ταξινόμηση του συστήματος με την ταξινόμηση του εξεταστή από την έμμεση οπτική παρατήρηση βρέθηκαν τιμές ευαισθησίας από 28,6% έως 100% (μ.ο. 57,3%), ειδικότητας από 56,7% έως 98,5% (μ.ο. 92,2%), ορθότητας από 8,3% έως 97,4% (μ.ο. 46,2%) ανάμεσα στις διάφορες κατηγορίες και η ακρίβεια του συστήματος 71,6%. Ο σταθμισμένος συντελεστής k υπολογίστηκε στο 0,761 ενώ η τιμή για το μη σταθμισμένο συντελεστή k βρέθηκε να είναι 0,601. Συμπεράσματα Τα αποτελέσματα δείχνουν ότι η χρήση αλγορίθμων για την αυτοματοποιημένη ανίχνευση και κατάταξη μασητικών τερηδονικών βλαβών σύμφωνα με το σύστημα ICDAS II από φωτογραφίες ενδοστοματικής κάμερας αποτελεί μια πολλά υποσχόμενη τεχνική. Απομένουν να γίνουν κάποιες επιπλέον τροποποιήσεις στην εκπαίδευση του αλγόριθμου, μετά από τις οποίες αναμένουμε μεγαλύτερες τιμές ευαισθησίας και ειδικότητας, καθώς και βελτίωση της επαναληψιμότητας και ακρίβειας του συστήματος.Introduction Numerous techniques have been developed to assess the caries status of occlusal surfaces in an attempt to provide supplementary assistance to the direct visual examination and eliminate the great divergence of decisions found between different practitioners or even the same practitioner when the same lesion is evaluated at different times. Aim The aim of this study is to apply and evaluate the reliability of an automated occlusal caries diagnostic system via algorithms on digital images acquired by teeth in vivo using an intraoral camera. Material and Methods The examiner was theoretically and practically trained using the standardization tools of the ICDAS II system and calibrated with the golden examiner by examining teeth intraorally and from photographs on the computer screen. Then their findings were compared until they reached an agreement of 98% (>85%). The sample consisted of 106 permanent molars belonging to patients treated at the postgraduate clinic of the Paediatric Dentistry department and the undergraduate clinic of the University of Athens. Teeth with developmental defects of the enamel or dentin were excluded from the study. Teeth were cleaned of organic residues and stains with a bristle brush, rinsed using air-water spray and dried for 5 seconds using air before every examination and photo shooting. Intraoral camera Carestream - CS 1200 was used for the photo shooting. Then, the examiner assessed the occlusal surfaces in vivo –direct observation- and after classifying each area of interest of the occlusal surface according to ICDAS II, the outline and code of the lesion was marked on a printed image acquired by the camera. The examiner reassessed the same teeth after 15 days from the digital images in the same way on the computer screen –indirect observation-. An application of algorithms developed in Java environment was used for the recording of the direct and indirect examination’s result. 86 of these images (with a number of 3024 superpixels) were used to train the algorithm. Then 20 different images containing multiple occlusal areas of interest were evaluated by the algorithm and the results were compared to the ones from the direct and indirect visual examination. Statistical analysis Data were processed and analyzed with STATA 12. The classification from the examiner (after direct and indirect observation) was compared with the classification from the algorithm. Overall proportion of agreement and a weighted and non-weighted version of kappa coefficient of agreement was calculated. Results Comparing the system’s classification to the examiner’s classification from the direct observation in the mouth we found the sensitivity ranging from 29.2% to 100% (mean 59.1%), the specificity ranging from 52.4% to 99.2% (mean 91.3%), the precision ranging from 11.1% to 95.4% (mean 49.9%) among the ICDAS II categories and system’s accuracy 74%. Kappa weighted value was calculated to 0.701 and kappa non-weighted value to 0.587. Comparing the system’s classification to the examiner’s classification from the indirect observation of the photographs we found the sensitivity ranging from 28.6% to 100% (mean 57.3%), the specificity ranging from 56.7% to 98.5% (mean 92.2%), the precision ranging from 8.3% to 97.4% (mean 46.2%) among the ICDAS II categories and system’s accuracy 71.6%. Kappa weighted value was calculated to 0.761 and kappa non-weighted value to 0.601. Conclusions The preliminary results indicated that using algorithms for the automated detection and classification of occlusal carious lesions according to ICDAS II system from photographs of an intraoral camera is a very promising and encouraging technique. There are some more adjustments to be made on the training of the algorithm, after which we are expecting to achieve higher numbers of sensitivity and specificity and improve the overall reproducibility and accuracy of the system

PROP-1 gene mutations in a 63-year-old woman presenting with osteoporosis and hyperlipidaemia

PROP-1 gene mutations have been reported as a cause of combined pituitary hormone deficiency. Physical and hormonal phenotypes of affected individuals are variable. We report a 63-year-old female who presented with osteoporosis. She was short, did not enter puberty spontaneously and had primary amenorrhea. Biochemical evaluation revealed secondary hypothyroidism and mixed hyperlipidaemia, while dynamic testing of pituitary function was diagnostic of hypopituitarism. Bone density in the lumbar spine disclosed osteoporosis. DNA analysis showed that the patient was homozygote for the R73H mutation of the PROP-1 gene. The unfavourable long-term course of an untreated patient with PROP-1 gene mutation emphasizes the need for early aetiologic classification and proper management and follow-up of patients with short stature and/or disturbances of pubertal development