Comparison of two methods for measuring the pubococcygeal line from sagittal-plane magnetic resonance imaging

Aims The pubococcygeal line (PCL) is an important reference line for determining measures of pelvic organ support on sagittal-plane magnetic resonance imaging (MRI); however, there is no consensus on where to place the posterior point of the PCL. As coccyx movement produced during pelvic floor muscle (PFM) contractions may affect other measures, optimal placement of the posterior point is important. This study compared two methods for measuring the PCL, with different posterior points, on T2-weighted sagittal MRI to determine the effect of coccygeal movement on measures of pelvic organ support in older women. Methods MRI of the pelvis was performed in the midsagittal plane, at rest and during PFM contractions, on 47 community-dwelling women 60 and over. The first PCL was measured to the tip of the coccyx (PCLtip) and the second to the sacrococcygeal joint (PCLjnt). Four measures of pelvic organ support were made using each PCL as the reference line: urethrovesical junction height, uterovaginal junction height, M-line and levator plate angle. Results During the PFM contraction the PCLtip shortened and lifted (P < 0.001); the PCLjnt did not change (P > 0.05). The changes in the four measures of pelvic organ support were smaller when measured relative to the PCLtip as compared to those to the PCLjnt (P < 0.001). Conclusions Coccyx movement affected the length and position of the PCLtip, which resulted in underestimates of the pelvic-organ lift produced by the PFM contraction. Therefore, we recommend that the PCL be measured to the sacrococcygeal joint and not to the tip of the coccyx

Identification of telomere dysfunction in Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is a progressive inherited neurodegenerative disorder caused by mutation of the FXN gene, resulting in decreased frataxin expression, mitochondrial dysfunction and oxidative stress. A recent study has identified shorter telomeres in FRDA patient leukocytes as a possible disease biomarker. Results: Here we aimed to investigate both telomere structure and function in FRDA cells. Our results confirmed telomere shortening in FRDA patient leukocytes and identified similar telomere shortening in FRDA patient autopsy cerebellar tissues. However, FRDA fibroblasts showed significantly longer telomeres at early passage, occurring in the absence of telomerase activity, but with activation of an alternative lengthening of telomeres (ALT)-like mechanism. These cells also showed accelerated telomere shortening as population doubling increases. Furthermore, telomere dysfunction-induced foci (TIF) analysis revealed that FRDA fibroblasts have dysfunctional telomeres. Conclusions: Our finding of dysfunctional telomeres in FRDA cells provides further insight into FRDA molecular disease mechanisms, which may have implications for future FRDA therapy.

Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

The real effects of banking supervision:evidence from enforcement actions

We present a novel way to examine macro-financial linkages by focusing on the real effects of bank supervisors’ enforcement actions. Exploiting plausibly exogenous variation in supervisory monitoring intensity, we show that enforcement actions in single-market banks trigger temporarily large adverse effects for the macroeconomy by reducing personal income growth, the number of establishments, and increasing unemployment. These effects are related to contractions in bank lending and liquidity creation, and are more pronounced when we consider enforcement actions on both single-market and multi-market banks, and in counties with fewer banks and greater external financial dependence.

Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

Pelvic-Floor Rehabilitation, Part 2 : Pelvic-Floor Reeducation With Interferential Currents and Exercise in the Treatment of Genuine Stress Incontinence in Postpartum Women : A Cohort Study

Background and Purpose. This descriptive cohort study investigated a physical therapy program of pelvic-floor neuromuscular electrostimulation (NMES) combined with exercises, with the aim of developing a simple, inexpensive, and conservative treatment for postpartum genuine stress incontinence (GSI). Subjects. Eight female subjects with urodynamically established GSI persisting more than 3 months after delivery participated in the study. The subjects ranged in age from 24 to 37 years (X̅=32, SD=4.2). Methods. This was a descriptive multiple-subject cohort study. Each subject received a total of nine treatment sessions during 3 consecutive weeks, consisting of two 15-minute sessions of NMES followed by a 15-minute pelvic-floor muscle exercise program. Patients also practiced daily pelvic-floor exercises during the 3-week treatment period. The treatment intervention was measured using three separate variables. Maximum muscle contractions (pretraining, during training, and posttraining) were measured indirectly as pressure, using perineometry. Urine loss pretraining and posttraining was measured by means of a Pad test. Self-reported frequency of incontinence was recorded daily throughout the period of the study, using a diary. Data were analyzed using a one-way repeated measures analysis of variance (ANOVA), a Wilcoxon signed-ranks test, and a Friedman two-way ANOVA by ranks. Results. The results indicated that maximum pressure generated by pelvic-floor contractions was greater and both the quantity of urine loss and the frequency of incontinence were lower following the implementation of the physical therapy program. Five subjects became continent, and three others improved. A follow-up survey 1 year later confirmed the consistency of these results. Conclusion and Discussion. The results suggest that the proposed physical therapy program may influence postpartum GSI. Further studies are needed to validate this simple, inexpensive, and conservative physical therapy protocol.

Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats

Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague–Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6-evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunction in IBS patients.

Pelvic-Floor Rehabilitation, Part 2 : Pelvic-Floor Reeducation With Interferential Currents and Exercise in the Treatment of Genuine Stress Incontinence in Postpartum Women : A Cohort Study

Background and Purpose. This descriptive cohort study investigated a physical therapy program of pelvic-floor neuromuscular electrostimulation (NMES) combined with exercises, with the aim of developing a simple, inexpensive, and conservative treatment for postpartum genuine stress incontinence (GSI). Subjects. Eight female subjects with urodynamically established GSI persisting more than 3 months after delivery participated in the study. The subjects ranged in age from 24 to 37 years (X̅=32, SD=4.2). Methods. This was a descriptive multiple-subject cohort study. Each subject received a total of nine treatment sessions during 3 consecutive weeks, consisting of two 15-minute sessions of NMES followed by a 15-minute pelvic-floor muscle exercise program. Patients also practiced daily pelvic-floor exercises during the 3-week treatment period. The treatment intervention was measured using three separate variables. Maximum muscle contractions (pretraining, during training, and posttraining) were measured indirectly as pressure, using perineometry. Urine loss pretraining and posttraining was measured by means of a Pad test. Self-reported frequency of incontinence was recorded daily throughout the period of the study, using a diary. Data were analyzed using a one-way repeated measures analysis of variance (ANOVA), a Wilcoxon signed-ranks test, and a Friedman two-way ANOVA by ranks. Results. The results indicated that maximum pressure generated by pelvic-floor contractions was greater and both the quantity of urine loss and the frequency of incontinence were lower following the implementation of the physical therapy program. Five subjects became continent, and three others improved. A follow-up survey 1 year later confirmed the consistency of these results. Conclusion and Discussion. The results suggest that the proposed physical therapy program may influence postpartum GSI. Further studies are needed to validate this simple, inexpensive, and conservative physical therapy protocol.

Determination of subclinical metabolic disorders in transition dairy cows

Das Gesundheitsmanagement von Milchkühen hat in den vergangenen Jahren auf den landwirtschaftlichen Betrieben an Bedeutung gewonnen. Neben Präventionsmaßnahmen zur Gesunderhaltung der Tiere ist die frühzeitige und systematische Erkennung von Erkrankungen hierbei der Hauptbestandteil. Es zeigt sich vermehrt, dass vor allem Transitkühe verstärkt an Stoffwechselerkrankungen in sowohl klinischer als auch subklinischer Form erkranken. Letztere stellen ein hohes Risiko dar, zum einen weil subklinische Erkrankungen oftmals nur schwer oder gar nicht erkannt werden und zum anderen, weil sie in vielen Fällen die Grundlage für meist schwerwiegendere Folgeerkrankungen sind. In der vorliegenden Studie wird das Thema der Früherkennung von subklinischen Ketosen und der subakuten Pansenazidose behandelt. Verschiedene Methoden wurden unter praktischen Versuchsbedingungen auf ihre Tauglichkeit zur Krankheitserkennung hin geprüft. In einer ersten Studie wurde auf einem konventionellen Milchviehbetrieb ein Ketose-Monitoring bei frischlaktierenden Kühen ab Tag 3 postpartum durchgeführt. Insgesamt 15 Tiere waren an einer subklinischen Ketose erkrankt, was eine Aufkommensrate von 26% in den untersuchten Tieren bedeutete. Die Blutproben von insgesamt 24 Tieren wurden auf ihren IL-6-Gehalt untersucht. Von den untersuchten Tieren waren 14 Tiere erkrankt, 10 Tiere bildeten die gesunde Kontrollgruppe. Interleukin-6 wurde bestimmt, da dem Zytokin IL-6 in anderen Studien in Bezug auf Ketosen eine Rolle zugesprochen wurde. Die erwartete Erhöhung von IL-6 bei erkrankten Tieren konnte nicht festgestellt werden; die erkrankten Kühe zeigten vielmehr die niedrigsten IL-6 Werte der Studiengruppe. Insgesamt waren die IL-6 Konzentrationen auf einem niedrigen Niveau mit 27.2 pg/m l± 10.2. Es zeigte sich, dass die IL-6 Bestimmung im Blut hinsichtlich der Erkennung von subklinischen Ketosen nur eingeschränkt nutzbar ist. Es konnte ausschließlich eine schwache negative Korrelation zwischen Beta- Hydroxybutyrat (BHBA, Goldstandard für den Nachweis einer Ketose) und IL-6 detektiert werden. Zusätzlich zu den Blutanalysen wurde ebenfalls die tägliche Wiederkauaktivität mit dem „DairyCheck“ System bestimmt, welches kontinuierlich die charakteristischen Kaumuskelkontraktionen aufzeichnet und somit die Dauer des Wiederkäuens bestimmt werden kann. Es wurde geprüft, ob sich ketotische Tiere von nicht ketotischen Tieren hinsichtlich der täglichen Wiederkäuzeit unterscheiden. Milchkühe mit einer Ketose kauten im Schnitt 475 min/d ± 56 wieder, nach Genesung 497 min/d ± 48. Sie befanden sich somit im Durchschnitt immer unterhalb der gesunden Kontrollgruppe, welche 521 min/d ± 76 wiederkaute. Eine Korrelation zwischen der Wiederkauzeit und dem BHBA- Gehalt im Blut war nur sehr schwach ausgeprägt, nicht zuletzt da die Tiere generell eine hohe Variabilität in der Wiederkauaktivität zeigten. Bei einer weiteren Studie, ebenfalls auf einem Praxisbetrieb durchgeführt, wurde auf die Erkennung der subakuten Pansensazidose (SARA) fokussiert. Hierbei kam ein drahtloses, kommerziell verfügbares Bolussystem zum Einsatz, welches den pH Wert kontinuierlich im Retikulorumen misst. Es macht die Erkennung einer SARA auch unter Praxisbedingungen ohne invasive Methoden wie der Punktion möglich. Das Bolussystem wurde 24 Milchkühen kurz vor der Abkalbung oral eingegeben, um den pH-Wert während der gesamten Transitphase messen und überwachen zu können. Während in der Trockenstehphase nur vereinzelte SARA Fälle auftraten, erlitt ein Großteil der untersuchten Tiere in der Frühlaktation eine SARA. Auf Grundlage von pH-Werten von laktierenden Milchkühen, wurde zusätzlich eine Sensitivitätsanalyse von verschieden, bereits eingesetzten Nachweismethoden durchgeführt, um die Tauglichkeit für die SARA-Diagnostik zu untersuchen. Es handelte sich hierbei zum einen um einen SARA-Nachweis unter Heranziehung von Einzelwerten, Fress- und Wiederkäuzeiten, sowie ausgewählten Milchinhaltsstoffen und der Milchmenge. Die Analyse ergab, dass nahezu alle Nachweismethoden im Vergleich zur Langzeitmessung nur eingeschränkt zur SARA-Diagnostik nutzbar sind. In einem weiteren Teil der Studie wurde eine Kotfraktionierung bei den gleichen Tieren durchgeführt, um damit SARA-Tiere auch mittels der Kotanalyse erkennen kann. Es konnte gezeigt werden, dass zum einen die Ration einen Einfluss auf die Kotzusammensetzung hat (Trockensteherration versus Ration für Laktierende) zum anderen aber auch, dass eine SARA die Zusammensetzung des Kotes verändert. Hierfür wurden Kotproben ausschließlich von laktierenden Kühen untersucht, sodass der Einfluss der Ration ausgeschlossen werden konnte. Erhöhte Faseranteile im Kot von SARA - Kühen gaben Hinweis auf eine verminderte Verdaulichkeit. Dabei erwies sich vor allem die Hemizellulose als guter Parameter, um auf eine SARA schließen zu können. Die Versuchsbedingungen ließen es ebenfalls zu, die pH-Verläufe der Tiere in der Frühlaktation zu untersuchen. Eine Clusteranalyse von pH-Werten der ersten 12 Tage postpartum zeigte, dass die untersuchten Tiere trotz gleicher Haltungs- und Fütterungsbedingungen unterschiedliche pH-Wert Verläufe entwickelten. So gab es eine Gruppe von Milchkühen, die den pH-Wert stabil halten konnte, während die restlichen pH-Abfälle in verschiedenen Verläufen und Intensitäten aufzeigten. Es konnte ebenfalls aufgezeigt werden, dass Tiere innerhalb der Testherde unterschiedliche Schweregrade der SARA entwickelten. Auch in dieser Studie wurde deutlich, dass Tiere scheinbar unterschiedliche Möglichkeiten haben, auf ihre Umwelt zu reagieren, bzw. suboptimalen Bedingungen entgegenwirken zu können. Zusammengefasst wurden verschiedene Methoden zur Ketose- und SARA- Erkennung geprüft, von denen nur einzelne für die Praxis zu empfehlen sind. Die Variabilität der Tiere, sowohl bei der Ausprägung der Erkrankungen als auch bei den gemessenen Parametern verdeutlicht die Notwendigkeit, diese im Herden- und Gesundheitsmanagement in Zukunft stärker zu berücksichtigen.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.

Pattern peristaltico uterino nell'adenomiosi isolata: studio prospettico

Obiettivi dello studio: valutare con l’ecografia transvaginale la peristalsi uterina in fase periovulatoria in donne con adenomiosi isolata, confrontandola con un gruppo di controllo e, secondariamente, valutare il grado di accordo tra gli sperimentatori nella descrizione dei pattern di contrattilità. Disegno dello studio: studio osservazione prospettico condotto presso il Policlinico S. Orsola- Malpighi di Bologna, Italia. Materiali e Metodi: sono state reclutate pazienti afferenti al Centro per valutazione ambulatoriale, suddivise sulla base dei criteri di inclusione ed esclusione nei gruppi A (adenomiosi) e B (controlli) e sono state sottoposte da un unico ecografista esperto a ecografia transvaginale con registrazione di un video della durata di 180 secondi della scansione sagittale dell’utero. La registrazione è stata rivalutata off line da due sperimentatori esperti ecografisti, non a conoscenza della storia clinica delle pazienti e in cieco l’uno rispetto all’altro, che hanno descritto il pattern contrattile. È stata stimata una numerosità campionaria di 18 pazienti per gruppo per ottenere una differenza del 20% nell’obiettivo primario con una significatività del 5% (power 80%). Risultati: di 51 pazienti reclutate nello studio, a seguito di drop out 36 sono state sottoposte alla videoregistrazione ecografica (18 per gruppo). Il pattern peristaltico nel gruppo A è risultato alterato in maniera statisticamente significativa rispetto al gruppo B con un p value= 0,02. Sono stati osservati un pattern retrogrado nel 27,8% vs 72,2%, anterogrado del 11,1% vs 16,7%, opposto 38,9% vs 5,6% e random nel 22,2% vs 5,6%, rispettivamente nel gruppo A e B. Il calcolo dell’accordo interosservatore ha portato a un κ value di 0,92. Conclusioni: l’adenomiosi isolata è associata a disperistalsi uterina, che concorrerebbe nello sviluppo dei sintomi tipici dell’adenomiosi. L’ecografia transvaginale rappresenta uno strumento accessibile e utile nella valutazione della contrattilità uterina in quanto il grado di accordo tra gli sperimentatori è ottimo.

Outcomes of global coagulation assays in patients with Philadelphia-negative myeloproliferative neoplasms with respect to genetic determinants of clonal progression

Classical myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders that manifest with inflammation, promotion of atherosclerosis, hypercoagulability, fibrosis, and clonal evolution. The complex biological background lends itself to multi-omics studies. We have previously shown that reduced platelet fibrinogen receptor (PFR) expression may follow hyperactivation of plasma-dependent mechanisms, such as tissue factor (TF) release, unbalanced thrombin generation, involvement of protease-activated receptors (PARs). Acetylsalicylic acid (ASA) helped to restore the expression of PFRs. In this study, we enrolled 53 MPN patients, subjecting them to advanced genetic testing (panel of 30 genes in NGS), global coagulation testing (Rotational Thromboelastometry - ROTEM) and cytofluorometric determination of PFRs. ROTEM parameters appear to differ considerably depending on the type of pathology under investigation, cell count, and selected mutations. Essential thrombocythemia (ET) and CALR mutation appear to correlate with increased efficiency of both classical coagulation pathways, with significantly more contracted clot formation times (CFTs). In contrast, primary myelofibrosis (PMF) and polycythemia vera (PV) show greater imbalances in the hemostatic system. PV, probably due to its peculiar hematological features, shows a lengthening of the CFT and, at the same time, a selective contraction of parameters in INTEM with the increase of platelets and white blood cells. PMF - in contrast - seems to exploit the extrinsic pathway more to increase cell numbers. The presence of DNMT3A mutations is associated with reduced clotting time (CT) in EXTEM, while ASXL1 causes reduced maximal lysis (ML). EZH2 could be responsible for the elongation of CFT in INTEM assay. In addition, increased PFR expression is associated with history of hemorrhage and sustained CT time in FIBTEM under ASA prophylaxis. Our findings corroborate the existing models on the connection between fibrosis, genetic complexity, clonal progression, and hypercoagulability. Global coagulation assays and PFR expression are potentially useful tools for dynamic evaluation of treatments’ outcomes.