Chromosome imbalances in syndromic hearing loss

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3–q25.2, 2q22q23, 6p25.3 and 11q13.2–q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14–27%), and the use of aCGH for defining disease etiology is recommended.     

Collaborative stepped care for anxiety disorders in primary care: aims and design of a randomized controlled trial

Background  

Panic disorder (PD) and generalized anxiety disorder (GAD) are two of the most disabling and costly anxiety disorders seen in primary care. However, treatment quality of these disorders in primary care generally falls beneath the standard of international guidelines. Collaborative stepped care is recommended for improving treatment of anxiety disorders, but cost-effectiveness of such an intervention has not yet been assessed in primary care. This article describes the aims and design of a study that is currently underway. The aim of this study is to evaluate effects and costs of a collaborative stepped care approach in the primary care setting for patients with PD and GAD compared with care as usual.     

Black Cumin Pressing Waste Material as a Functional Additive for Starch Bread

The aim of the study was to determine the effect of the addition of black cumin (Nigella sativa L.) pressing waste (BCW) and black cumin seeds (BCS) on the properties of starch bread. The control bread was prepared from wheat starch (100%) with a gluten-free certificate, plantain husk (5%), and guar gum (2%). BCS and BCW were added between 0 and 10% of wheat starch. We determined the physicochemical properties, color, texture, and sensory properties of the prepared bread. Gas chromatography–mass spectrometry (GC–MS) analysis was performed to detect the phenolic compounds in the bread. The bread prepared with 6% BCS and 4% BCW had a significantly higher volume than the starch control bread did. Sensory analysis (taste) showed that BCS and BCW could be added up to 4% and 8%, respectively. The addition of BCS and BCW reduced the brightness of the crumb. A significant decrease in the L * index of the crumb was observed from 50.9 for the control bread to 34.1 and 34.0 for bread with 10% BCS and BCW, respectively. The addition of BCS and BCW decreased the hardness, elasticity, and chewiness of the starch bread crumb. Starch bread enriched with BCS and BCW was characterized by a higher content of 2-hydroxybenzoic acid, 2-hydroxyphenyl acetic acid, and 4-hydroxyphenyl acetic acid.     

Effect of plasma on composition of human enamel and cementum pellicle

Abstract – Slabs of human enamel and cementum were incubated with plasma alone or with various mixtures of plasma and saliva. Proteins and glycoproteins that adsorbed to the surface of the slabs in 0 to 60 min were labeled by lactoperoxidase-catalyzed ¹²⁵I-iodination and by mild periodate oxidation followed by NaB³H₄ reduction. The labeled components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by autoradiography or fluorography. From plasma alone, a 58 and a 66 kDa protein (probably albumin) were adsorbed to the enamel surface in relatively equal amounts, but no ¹²⁵I-labeled components were detected on the cementum surface in the absence of saliva. Adding 10% saliva to the incubation mixture promoted the adsorption of the 58 and 66 kDa components to cementum. In addition, another set of proteins, including components of 44, 47, 29, and 25 kDa, was adsorbed to both cementum and enamel in the presence of saliva. These six proteins were the major ¹²⁵I-labeled species in all of the pellicles formed from mixtures of plasma and saliva. The electrophoretic mobility of the major 120 and 140 kDa ³H-labeled sialoglycoproteins adsorbed to both cementum and enamel was similar to that of the low-molecular-weight mucin of submandibular/sublingual saliva.     

ACTH and enkephalin axonal input to paraventricular neurons containing c-fos-like immunoreactivity.

The presence of c-fos like protein in neuronal nuclei has been observed in several areas of the central nervous system. It is associated with activation of these neurons by specific stimuli, in particular stressful stimuli. The present study investigated the expression of c-fos-like immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus following stimulation of small diameter, nociceptive afferents in the hindfoot of the rat. The afferent innervation to these c-fos containing PVN neurons was examined in order to identify putative neurotransmitters which might modulate the activity of stress responsive, i.e. c-fos containing neurons in the PVN. Adrenocorticotropic releasing hormone (ACTH), enkephalin (ENK), and corticotropin releasing factor (CRF), peptides whose functions have been related to the regulation of stress behavior, were selected to investigate their potential innervation of c-fos immunolabeled neurons. Analysis of immunocytochemically double-labeled vibratome and semi-thin plastic-embedded sections revealed that ACTH and ENK immunoreactive axonal varicosities were present in close anatomical proximity to a substantial number of parvocellular PVN neurons that contained c-fos in response to noxious stimulation. Few c-fos containing PVN neurons were apposed by CRF axonal varicosities. The resulting data show that a large number of c-fos immunoreactive PVN neurons, though not the majority, is innervated by ACTH and ENK. This suggests that the activity of stress responsive, c-fos expressing neurons can substantially be modulated and regulated by ACTH and ENK and to a lesser degree by CRF.     

A Review of Methods Used to Reinforce Polymethyl Methacrylate Resin

Various methods to reinforce acrylic denture base material have been used to repair fractures in complete dentures. Metal wires and plates have been tested as reinforcement of polymethyl methacrylate (PMMA) resin. The contributions of the studies conducted on this biphase composite system are discussed in this review article. The literature has reported that even thin metal wires incorporated into the PMMA matrix increased the transverse strength of the PMMA construction. Metal mesh inserted into PMMA resin had negligible effects on the transverse strength of the restoration. Macroscopic retention of the metal strengtheners to the PMMA had only a minor effect on the strength in contrast to microscopic retention, which showed a more marked effect. Chemical bonding between the PMMA and metal reinforcer enhanced the strength of the prosthesis with some exceptions.     

ROLE OF THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IN CARDIOVASCULAR REGULATION

1. The paraventricular hypothalamic nucleus (PVH) is a complex structure with both neuroendocrine and autonomic functions. It is a major source of vasopressin and the primary source of corticotropin-releasing factor. In addition, parvicellular PVH neurons have reciprocal connections with brain-stem autonomic centres and directly innervate sympathetic preganglionic neurons. Evidence is reviewed which indicates that in conscious rats PVH activation increases blood pressure, heart rate, renal nerve activity and plasma renin activity. 2. In conscious rats, a non-hypotensive haemorrhage (13 mL/kg blood loss over 24 min) results in increased numbers of Fos-immunoreactive cell nuclei within both magnocellular and parvicellular PVH neurons, including the ventral medial parvicellular regions known to contain neuronal projections to brainstem autonomic centres and spinal cord sympathetic preganglionic neurons. 3. Cell-selective ibotenate lesions of the parvicellular PVH significantly blunt the corticosterone response but do not alter blood pressure, heart rate or plasma renin concentration response to non-hypotensive or hypotensive haemorrhage. This and earlier studies indicate that, while the PVH is necessary for the corticosterone response and contributes to increased vasopressin release during blood loss, it does not play an important role in the sympathetic nervous system and renin-angiotensin responses to hypovolaemia and hypotension. 4. There is evidence to indicate that the parvicellular PVH serves as a necessary relay for cardiovascular and renin responses to certain behavioural stressors. We propose that cardiovascular information relayed to parvicellular PVH autonomic regions may be used to modulate behavioural, rather than homeostatic, effects on haemodynamics and renin release.     

Pregnancy alters lateral parabrachial nucleus but not hypothalamic Fos expression following hypotensive hemorrhage

The goal of these experiments was to determine if hemorrhage-induced Fos expression in the hypothalamus and lateral parabrachial nucleus (LPBN) is altered by reproductive cycle phase or pregnancy. Conscious unrestrained female Sprague-Dawley rats were subjected to a 16 ml/kg hemorrhage on the morning of the metestrus or proestrus phases of the estrous cycle, or on day 12-14 of pregnancy (mid-gestation). Hemorrhage induced a significant increase (p < 0.01) in the number of Fos-immunoreactive cell nuclei in the supraoptic nucleus, and in both the magnocellular and parvicellular components of the paraventricular hypothalamic nucleus, that did not differ between groups. In virgin females, hemorrhage also induced a significant increase in LPBN Fos expression that did not differ between metestrus and proestrus. In pregnant animals, there was an increase in basal LPBN Fos expression, but hemorrhage induced no further increase in the number of Fos-immunoreactive neurons in the LPBN. Mean arterial pressure decreased (p < 0.001) and plasma renin activity increased (p < 0.01) to a similar extent in all three groups after 16 ml/kg blood loss. In summary, the number of paraventricular and supraoptic nucleus neurons activated by hemorrhage is unaffected by estrous cycle phase or pregnancy. In contrast, pregnancy significantly attenuates the LPBN response to hemorrhage.     

Dacryocystography: comparison of water-soluble and oil-based contrast agents

Dacryocystography has been widely used in the assessment of the nasolacrimal duct system, particularly in patients with epiphora. Our study was undertaken to evaluate image quality and level of patient discomfort during examinations with water-soluble contrast agents (iohexol [Omnipaque 240], iopamidol [Isovue 200 and 300], and 52.7% diatrizoate meglumine and 26.9% iodipamide meglumine [Sinografin]) compared with the iodized oil-based contrast agent Lipiodol. Fifty-five dacryocystograms were obtained from 41 consecutive patients. The procedure was performed first with a water-soluble contrast agent, then repeated with Lipiodol. A distention technique was used with conventional radiography. Patients were asked to evaluate their level of discomfort (none, mild, moderate, severe). The images were evaluated separately by two radiologists, blinded to which water-soluble agent was employed, and the images were graded on a five-point scale. Images obtained with Lipiodol were significantly better than those with other agents (P less than .02), and image quality deteriorated as iodine concentration decreased. Use of Isovue 300 and Sinografin produced significantly more patient discomfort (P less than .03) than the use of other agents. The authors conclude that, in most instances, Lipiodol is the contrast agent of choice with regard to both highest level of patient comfort and greatest conventional radiographic image quality among the agents compared.     

Differential etoposide sensitivity of cells deficient in the Ku and DNA- PKcs components of the DNA-dependent protein kinase

Etoposides block cell division by interfering with the action of topoisomerase II, leaving enzyme-DNA double-strand breaks. We found that certain components of the trimeric DNA-dependent protein kinase influence cell survival following etoposide damage. Interestingly, either Ku70- or Ku80-deficient cell lines, but not mutant cell lines of the DNA-PK catalytic sub-unit (DNA-PKcs), were found to be hypersensitive to the effects of etoposide VP16. Ku70- and Ku80- deficient cells can be complemented to an etoposide resistant phenotype by introducing wildtype Ku70 or Ku80 cDNAs. Mutational analysis of introduced Ku70 cDNAs into murine embryonic stem cells deleted for Ku70 (-/-) showed that mutants where heterodimerization and DNA binding functions of Ku were disrupted, also blocked the restoration of etoposide resistance. In contrast with the differential etoposide sensitivity of DNA-PK mutants, both Ku- and DNA-PKcs-deficient cell lines showed G2 ionizing radiation-induced delays, a cell cycle phase where topoisomerase II function is critical. Thus, the topoisomerase II cleaved complexes may be an example of DNA lesions requiring the Ku heterodimer, but not DNA-PK for DNA repair.