Perceptual analysis of speech and the activity in the lateral pharyngeal walls before and after velopharyngeal flap surgery

The purpose of this study was to investigate the effects of velopharyngeal flap surgery on speech and its relation with the activity in the lateral pharyngeal wall. Videofluoroscopic recordings made before and after operation were used in this retrospective study, which comprised 28 patients who had pharyngeal flap surgery between 5:5 and 14:3 (mean 8:6) years:months of age at the Sahlgrenska University Hospital, Göteborg, Sweden. Twenty-four patients had different types of clefts and four had velopharyngeal impairment (VPI) without a cleft palate. Eleven had additional malformations. Speech and activity in the lateral pharyngeal walls were rated perceptually preoperatively and postoperatively. The study confirmed that patients with VPI can be helped by a velopharyngeal flap operation. There seemed to be a relation with the activity in the lateral pharyngeal wall and speech. The later the postoperative assessment, the better the speech, but the age at operation did not affect the result. The impact of additional anomalies and syndromes should be investigated further.     

The long-term stability of temperament traits measured after a suicide attempt. A 5-year follow-up of ratings of Karolinska Scales of Personality (KSP)

The main aim of the present study was to investigate whether or not temperament dimensions are stable over time. Twenty-six patients (21 women and five men) filled in the Karolinska Scales of Personality (KSP) both at admission after a suicide attempt (index) and at follow-up 5 years later. KSP changes were significantly associated with low severity of psychiatric symptoms and no reported reattempts at follow up. There were significant changes of all five groups of KSP, most prominently in anxiety-related scales. At index, KSP scores did not differ between those who later would repeat a suicide attempt (repeaters) and not, but repeaters more often tended to have a personality disorder and their 24-h urinary cortisol tended to be lower. In this limited sample, repeaters seem to have a protracted high anxiety level as mirrored by high and stable KSP scores over time.     

Role of the lipopolysaccharide-CD14 complex for the activity of hemolysin from uropathogenic Escherichia coli

Bacterial pathogens produce a variety of exotoxins, which often become associated with the bacterial outer membrane component lipopolysaccharide (LPS) during their secretion. LPS is a potent proinflammatory mediator; however, it is not known whether LPS contributes to cell signaling induced by those microbial components to which it is attached. This is partly due to the common view that LPS present in bacterial component preparations is an experimental artifact. The Escherichia coli exotoxin hemolysin (Hly) is a known inducer of proinflammatory signaling in epithelial cells, and the signal transduction pathway involves fluctuation of the intracellular-Ca(2+) concentration. Since LPS is known to interact with Hly, we investigated whether it is required as a cofactor for the activity of Hly. We found that the LPS/Hly complex exploits the CD14/LPS-binding protein recognition system to bring Hly to the cell membrane, where intracellular-Ca(2+) signaling is initiated via specific activation of the small GTPase RhoA. Hly-induced Ca(2+) signaling was found to occur independently of the LPS receptor TLR4, suggesting that the role of LPS/CD14 is to deliver Hly to the cell membrane. In contrast, the cytolytic effect triggered by exposure of cells to high Hly concentrations occurs independently of LPS/CD14. Collectively, our data reveal a novel molecular mechanism for toxin delivery in bacterial pathogenesis, where LPS-associated microbial compounds are targeted to the host cell membrane as a consequence of their association with LPS.     

Relationship between peroxisome proliferator‐activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells

Peroxisome proliferator‐activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high‐performance liquid chromatography–tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04–4.1%) with absolute cellular concentrations in the range 4–2500 ng mg^?1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short‐chain (perfluorobutanoate and perfluoropentanoate) and long‐chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short‐chain homologs compared to the long‐chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5‐fold compared to controls. The concentration–response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound‐specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs.     

Oral health in children and adolescents with myotonic dystrophy

Myotonic dystrophy or dystrophia myotonica (DM) is a hereditary neuromuscular multisystem disease with a varying clinical expressivity and severity. The objective of this study was to assess the oral health in children with myotonic dystrophy and to compare it with a control group. Fifty-six DM patients, aged 2.7-18.0 yr, were compared with age- and gender-matched control patients with respect to caries, plaque, and gingivitis. Oral function and signs of temporomandibular dysfunction (TMD) were assessed, and the ability to co-operate in dental treatment was estimated. Questionnaires concerning eating habits, dental care, traumatic injuries to teeth, and orofacial function were also used. The DM patients had significantly more caries, plaque, and gingivitis than did control patients. They had more TMD problems and lower co-operation ability than the healthy control persons. General sedation was frequently needed to carry through dental treatment. DM patients are at risk of caries, gingivitis and TMD problems, and need intensified prophylactic care. Behavior management problems are common.     

alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis

Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone alphaB-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA-mediated knockdown of alphaB-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. alphaB-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in alphaB-crystallin(-/-) mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in alphaB-crystallin(-/-) mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate alphaB-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of angiogenic modulators.