Congenital Nasal Pyriform Aperture Stenosis as a rare manifestation of Trisome 8 Mosaicsm: a case report

Congenital Nasal Pyriform Aperture Stenosis (CNPAS) is an extremely rare cause of nasal airway obstruction. Clinically, it mimics choanal atresia in neonate. It needs to be differentiated because management differs from each. Pyriform aperture is located at the most anterior part of the nose and is always the narrowest region of the nasal cavity. Therefore, nasal obstruction can easily occur if there is slight decrease in its cross sectional area. CNPAS rarely presents alone. Usually, it arises together with a midline developmental defect such as holoprosencephaly or pituitary defect. We present the first ever reported case of CNPAS, in association with Trisomy 8 Mosaicsm (T8M)

Retropharyngeal abscess: seven-year review - clinical presentation, diagnosis and management

This was a retrospective study of operative records between 2000 – 2007 from two ear, nose and throat (ENT) referral centers in Malaysia to review demographic patterns, clinical presentations and management of retropharyngeal abscess (RPA). Our case series comprised of eight patients with five females and three males with a median age at presentation of 47 years. Comorbid factor in this series was diabetes mellitus, with four patients having diabetes. There were three cases of fish bone ingestion. The commonest presentation was dysphagia or odynophagia. None of them had fever. All patients were treated with broad spectrum intravenous antibiotics (IV) and drainage was performed for the abscess. Four patients underwent transoral drainage with three having the cervical approach and one having spontaneous rupture.All patients recovered well from the infection and only one patient passed away due to septicaemia. In conclusion, patients with retropharyngeal abscess may present with vague symptoms of sore throat, odynophagia without fever due to partial antibiotics treatment. A correct diagnosis should be made so that adequate treatment can be given to prevent mortality

Does direction of results of abstracts submitted to scientific conferences on drug addiction predict full publication?

<p>Abstract</p> <p>Background</p> <p>Data from scientific literature show that about 63% of abstracts presented at biomedical conferences will be published in full. Some studies have indicated that full publication is associated with the direction of results (publication bias). No study has looked into the occurrence of publication bias in the field of addiction.</p> <p>Objectives</p> <p>To investigate whether the significance or direction of results of abstracts presented at the major international scientific conference on addiction is associated with full publication</p> <p>Methods</p> <p>The conference proceedings of the US Annual Meeting of the College on Problems of Drug Dependence (CPDD), were handsearched for abstracts of randomized controlled trials and controlled clinical trials that evaluated interventions for prevention, rehabilitation and treatment of drug addiction in humans (years searched 1993–2002). Data regarding the study designs and outcomes reported were extracted. Subsequent publication in peer reviewed journals was searched in MEDLINE and EMBASE databases, as of March 2006.</p> <p>Results</p> <p>Out of 5919 abstracts presented, 581 met the inclusion criteria; 359 (62%) conference abstracts had been published in a broad variety of peer reviewed journals (average time of publication 2.6 years, SD +/- 1.78). The proportion of published studies was almost the same for randomized controlled trials (62.4%) and controlled clinical trials (59.5%) while studies that reported positive results were significantly more likely to be published (74.5%) than those that did not report statistical results (60.9%.), negative or null results (47.1%) and no results (38.6%), Abstracts reporting positive results had a significantly higher probability of being published in full, while abstracts reporting null or negative results were half as likely to be published compared with positive ones (HR = 0.48; 95%CI 0.30–0.74)</p> <p>Conclusion</p> <p>Clinical trials were the minority of abstracts presented at the CPDD; we found evidence of possible publication bias in the field of addiction, with negative or null results having half the likelihood of being published than positive ones.</p

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>cultivation of <it>Plasmodium falciparum </it>is usually carried out through the continuous preservation of infected erythrocytes deposited in static thin layers of settled haematocrit. This technique, called the candle-jar method, was first achieved by Trager and Jensen in 1976 and has undergone slight modifications since then. However, no systematic studies concerning the geometry of the haematocrit layer have been carried out. In this work, a thorough investigation of the effects of the geometric culturing conditions on the parasite's development is presented.</p> <p>Methods</p> <p>Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model.</p> <p>Conclusion</p> <p>In line with the results, a mechanism governing the propagation of the infection which limits it to the vicinity of the interface between the haematocrit layer and the culture medium is deduced, and the most appropriate configurations are proposed for further experimental assays.</p

Effects of Different Up-Dosing Regimens for Hymenoptera Venom Immunotherapy on Serum CTLA-4 and IL-10

BACKGROUND: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is involved in the activation pathways of T lymphocytes. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy. OBJECTIVE: to assess the effects on CTLA-4 of venom immunotherapy, given with different induction protocols: conventional (6 weeks), rush (3 days) or ultra rush (1 day). METHODS: Sera from patients with hymenoptera allergy were collected at baseline and at the end of the induction phase. CTLA-4 and IL-10 were assayed in the same samples. A subset of patients were assayed also after 12 months of VIT maintenance. RESULTS: Ninety-four patients were studied. Of them, 50 underwent the conventional induction, 20 the rush and 24 the ultra-rush. Soluble CTLA-4 was detectable in all patients at baseline, and significantly decreased at the end of the induction, irrespective of its duration. Of note, a significant decrease of sCTLA-4 could be seen already at 24 hours. In parallel, IL-10 significantly increased at the end of the induction. At 12 months, sCTLA-4 remained low, whereas IL-10 returned to the baseline values. CONCLUSIONS: Serum CTLA4 is an early marker of the immunological effects of venom immunotherapy, and its changes persist after one year of maintenance treatment

Effects of degree and timing of social housing on reversal learning and response to novel objects in dairy calves

Rodents and primates deprived of early social contact exhibit deficits in learning and behavioural flexibility. They often also exhibit apparent signs of elevated anxiety, although the relationship between these effects has not been studied. To investigate whether dairy calves are similarly affected, we first compared calves housed in standard individual pens (n = 7) to those housed in a dynamic group with access to their mothers (n = 8). All calves learned to approach the correct stimulus in a visual discrimination task. Only one individually housed calf was able to re-learn the task when the stimuli were reversed, compared to all but one calf from the group. A second experiment investigated whether this effect might be explained by anxiety in individually housed animals interfering with their learning, and tested varying degrees of social contact in addition to the complex group: pair housing beginning early (approximately 6 days old) and late (6 weeks old). Again, fewer individually reared calves learned the reversal task (2 of 10 or 20%) compared to early paired and grouped calves (16 of 21 or 76% of calves). Late paired calves had intermediate success. Individually housed calves were slower to touch novel objects, but the magnitude of the fear response did not correlate with reversal performance. We conclude that individually housed calves have learning deficits, but these deficits were not likely associated with increased anxiety

1B/(−)IRE DMT1 Expression during Brain Ischemia Contributes to Cell Death Mediated by NF-κB/RelA Acetylation at Lys310

The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-κB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-κB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post-ischemic neuronal damage. Both in mice subjected to transient middle cerebral artery occlusion (MCAO) and in neuronally differentiated SK-N-SH cells exposed to oxygen-glucose-deprivation (OGD), 1A/DMT1 was only barely expressed while the 1B/DMT1 without iron-response-element (−IRE) protein and mRNA were early up-regulated. Either OGD or over-expression of 1B/(−)IRE DMT1 isoform significantly increased iron uptake, as detected by total reflection X-ray fluorescence, and iron-dependent cell death. Iron chelation by deferoxamine treatment or (−)IRE DMT1 RNA silencing displayed significant neuroprotection against OGD which concomitantly decreased intracellular iron levels. We found evidence that 1B/(−)IRE DMT1 was a target gene for RelA activation and acetylation on Lys310 residue during ischemia. Chromatin immunoprecipitation analysis of the 1B/DMT1 promoter showed there was increased interaction with RelA and acetylation of H3 histone during OGD exposure of cortical neurons. Over-expression of wild-type RelA increased 1B/DMT1 promoter-luciferase activity, the (−)IRE DMT1 protein, as well as neuronal death. Expression of the acetylation-resistant RelA-K310R construct, which carried a mutation from lysine 310 to arginine, but not the acetyl-mimic mutant RelA-K310Q, down-regulated the 1B/DMT1 promoter, consequently offering neuroprotection. Our data showed that 1B/(−)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-κB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke-induced neuronal damage