Speech in Sri Lankan cleft palate subjects with delayed palatoplasty.

This investigation was undertaken within the context of the Sri Lankan Cleft Up and Palate Project, probably the largest surgical and research programme to date concerned with the late operated cleft lip and/or palate subject (Mars et al., 1990). This study examines the speech results of88 patients who received palatal surgery by a visiting British surgical team. The main cohort, consisting of 67 nonsyndromic cleft lip and/or palate Sinh ala speaking patients over the age of eight years at palate repair, have been studied longitudinally. All these patients have pre-operative, post-operative, and post-therapy speech recordings. In addition, 21 similar patients below the age of eight years at surgery have been partially examined. 51 patients have further speech recordings at 4 or 5 years post-operatively. Investigations of velopharyngeal function were undertaken using lateral skull X-rays of patients phonating "ee', nasopharyngoscopy, and a perceptual assessment. Post-operative intra-oral examinations were also carried out. A unique method of speech analysis has been devised, and is used to describe the speech results. The results have shown that patients who have established their speech with an unrepaired palate usually have severely disordered speech, with the exception of some patients with less severe clefts. Post-operatively, many patients retain these poor speech patterns, even with some speech therapy support. Post-therapy, only one third of the cohort had normal or near-normal speech, none of whom were adults. The value of palatal closure is very limited if regular speech therapy is not available as a follow-up to surgery. Only 20% of the cohort achieved post-operative velopharyngeal closure, suggesting that palatoplasty is an inadequate surgical procedure for the majority of patients, in particular those who present with major clefts and are older than eight years of age at surgery. The important variables affecting outcome are palatal repair, speech therapy intervention, age, cleft type, nature of pre-operative speech, and nature of surgery. Structural factors in particular velopharyngeal function and also possibly fistulae, in the adult group, are further relevant variables. Criteria for selecting patients for surgery within this type of environment are proposed

Nebenwirkungen von Sanktionen: Kulturelle Beziehungen mit Iran, Kuba, Russland und Belarus

Die vorliegende Studie untersucht, wie sich internationale Sanktionen als häufig angewandtes Mittel der Außenpolitik auf die kulturellen Beziehungen zwischen Deutschland und sanktionierten Staaten auswirken. Dazu werden in vier Fallstudien - Iran, Kuba, Russland und Belarus - Mittlerorganisationen und Kulturschaffende in den Blick genommen. Die Studie analysiert dabei (oftmals unbeabsichtigte) materielle Folgen und sogenannte mentale Effekte, die Sanktionen auf den Kulturaustausch haben können. Insgesamt erweist es sich als schwierig, die Effekte von Sanktionen auf kulturelle Beziehungen klar von innenpolitischen Entwicklungen sowie einer allgemeinen Verschlechterung der Beziehung zwischen Deutschland und dem jeweiligen Zielland zu trennen. Die Analyse zeigt nichtsdestotrotz, dass auch gezielte Sanktionen, die sich auf Entscheidungsträger oder bestimmte Wirtschaftsbereiche konzentrieren, von Kulturschaffenden und Wissenschaftlern1 als Einschnitt und Kooperationshemmnis wahrgenommen werden können. Oftmals steigt auch das Misstrauen der Behörden in den Zielländern gegenüber unabhängigen Kulturschaffenden. Zudem wirken sich die wirtschaftlichen Folgen von Sanktionen unbeabsichtigt auch auf Kulturprojekte aus. In allen vier Fallstudien versuchen die sanktionierten Regierungen zudem, externe Sanktionen als Legitimationsressource für sich und ihre Politik zu nutzen. Gleichzeitig sind jedoch auch verstärkte Bemühungen - von Kulturschaffenden sowohl in Deutschland als auch im Zielland - zu verzeichnen, einer Verringerung des Austauschs entgegenzuwirken. Trotz dieser Schwierigkeiten haben Kulturbeziehungen großes Potenzial, das Gespräch zwischen Gesellschaften angesichts eines politischen Konflikts aufrechtzuerhalten. Die Studie empfiehlt daher, im Fall von externen Sanktionierungen die Kulturbeziehungen mit dem jeweiligen Zielland verstärkt zu fördern und hier vor allem, so weit möglich, nichtstaatliche Akteure zu unterstützen

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART

Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and consequently which of the three major SOX5 protein isoforms are affected. One intragenic deletion involving only untranslated exons was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene