Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency

Human FOXP2 deficiency has been identified as a cause of hereditary developmental verbal dyspraxia. Another member of the same gene family, FOXP1, has expression patterns that overlap with FOXP2 in some areas of the brain, and FOXP1 and FOXP2 have the ability to form heterodimers. These findings suggest the possibility that FOXP1 may also contribute to proper speech development. However, no such role of FOXP1 has been established to date. Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges. The nature of the speech deficit is different from the primary oromotor verbal dyspraxia found in patients with FOXP2 deficiency. The patient''s developmental deficits may support a role for FOXP1 in the development of verbal and motor skills.     

Oral acute toxicity study as well as tissues oxidative stress and histopathological disorders in edible camphor administered rats

In the South-western part of Nigeria, edible camphor (EC) infusions are used to treat pile, back pain, and erectile dysfunction, especially in preparation for sexual intercourse. We therefore carried out oral acute toxicity study, and then investigated the effects of various doses of EC on the activities of lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD), as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels in wistar rats. Oral LD₅₀ of EC was estimated to be 9487 mg/kg body weight. Based on this, thirty animals were divided into six groups of five rats each, and were orally administered various doses of EC (1, 2, 4, and 6 g/kg body weight) for seven days. Comparing all results with control, EC significantly increased serum LDH activity (4 and 6 g/kg), liver (6 g/kg) and kidney (4 and 6 g/kg) MDA levels, as well testis GSH levels (1 g/kg). CAT activities were significantly decreased in liver, kidney, and testis, and also lung GSH level by all the tested doses. For SOD, activities were significantly increased in liver and lung, but significantly decreased in kidney (2, 4, and 6 g/kg). Various pathological disorders were also seen following the various doses of EC administered, especially in liver, kidney and lung. Therefore, from our findings, it is evident that incessant, misuse or overconsumption of EC could lead to oxidative tissue damage in rats.     

Rates of infection for single-lumen versus multilumen central venous catheters: a meta-analysis

OBJECTIVE: Since the introduction of multilumen central venous catheters two decades ago, there has been controversy whether the additional lumens place patients with these catheters at higher risk for infection. Our objective was to determine the risk of catheter-related bloodstream infection (CRBSI) and catheter colonization in multilumen catheters compared with single-lumen catheters. DATA SOURCE: Studies were identified by a computerized search of MEDLINE, EMBASE, CINAHL, Current Contents, and PREMEDLINE databases and by review of bibliographies and expert consultation. Studies comparing the prevalence of CRBSI or catheter colonization among single-, double-, and triple-lumen central venous catheters were included. We excluded studies if they included central venous catheters that were long-term, cuffed, tunneled, or coated with antibiotic or antiseptic agents. DATA ABSTRACTION: Two independent reviewers abstracted data on: 1) risk factors for CRBSI and colonization, 2) outcome definitions used, 3) the absolute prevalence of CRBSI and catheter colonization, and 4) study design and quality. DATA SYNTHESIS: A total of 15 studies met inclusion criteria. Summary odds ratios were calculated using a random-effects model. Although CRBSI was more common in multilumen catheters (summary odds ratios, 2.15; 95% confidence interval, 1.00-4.66), catheter colonization was not (summary odds ratios, 1.78; 95% confidence interval, 0.92-3.47). Tests for heterogeneity, however, suggested substantial variation by study. When only studies of higher quality were included, multilumen catheters were found not to be associated with a significant increase in CRBSI prevalence (summary odds ratios, 1.30; 95% confidence interval, 0.50-3.41). CONCLUSIONS: Multilumen central venous catheters may be associated with a slightly higher risk of infection when compared with single-lumen catheters; however, this relationship diminishes when only high-quality studies that control for patient differences are considered. The slight increase in infectious risk when using multilumen catheters is likely offset by their improved convenience, thereby justifying the continued use of multilumen vascular catheters.     

Detection of Clostridium botulinum type A toxin by enzyme-linked immunosorbent assay with antibodies produced in immunologically tolerant animals.

Immunological tolerance is a state of unresponsiveness to foreign substances (antigens) which can develop in human and animal species as the result of continued exposure to antigens early in life. We utilized this principle for the preparation of antibodies against Clostridium botulinum type A toxin. By selective suppression of the immunological response of rabbits to unwanted antigens and subsequent immunization with a toxoid, we were able to produce a specific type A antitoxin without the need to purify the toxin. Despite cross-reactivity with C. botulinum type B, our type A antitoxin was otherwise specific since it did not react with culture filtrates of nontoxigenic variants of type B, any other C. botulinum type (C, D, E, F, and G), nor with 18 other Clostridium species, including Clostridium sporogenes. Using this antitoxin, we developed a sensitive enzyme-linked immunosorbent assay for detection of C. botulinum type A toxin.     

Can phages cause Alzheimer’s disease?

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with progressive dementia. Multiple processes have been implicated in AD, notably including abnormal beta-amyloid production, tau hyperphosphorylation and neurofibrillary tangles (NFTs), synaptic pathology, oxidative stress, inflammation, protein processing or misfolding, calcium dyshomeostasis, aberrant reentry of neurons into the cell cycle, cholesterol synthesis, and effects of hormones or growth factors. The complexity of the disease, which affects numerous molecules, cells, and systems and impedes attempts to determine which alterations are specifically associated with early pathology. Chlamydia pneumoniae is an obligate intracellular bacterium. Infection with this organism has been suggested to be a risk factor for AD. C. pneumoniae has two phages phiCPAR39 and phage related to phiCPG1. HYPOTHESIS: we propose that these two phages by entering into mitochondria of chlamydia's host cell can work as slow viruses and can initiate AD.     

Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest

We previously showed that inhibition of protein kinase C delta (PKCδ) improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days after arrest. Therefore, in this study, we investigate the mechanism of action of PKCδ-mediated hypoperfusion after ACA in the rat by using the two-photon laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF) and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence of δV1-1 (specific PKCδ inhibitor), nitric oxide synthase (NOS) substrate (L-arginine, L-arg) and inhibitor (N^ω-Nitro-L-arginine, NLA), and nitric oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional LDF and local (TPLSM) CBF in the presence of δV1-1+L-arg, but only an increase in regional CBF under δV1-1+SNP treatments. Systemic blood nitrite levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were enhanced by pretreatment with δV1-1 30 minutes before ACA possibly attributable to enhanced endothelial NOS protein levels. Our results suggest that PKCδ can modulate NO machinery in cerebral vasculature. Protein kinase C delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but can be reversed with δV1-1 improving brain perfusion, thus providing subsequent neuroprotection after ACA.