Neurofilament light chain and dorsal root ganglia injury after adeno-associated virus 9 gene therapy in nonhuman primates.

In nonhuman primates (NHPs), adeno-associated virus serotype 9 (AAV9) vectorized gene therapy can cause asymptomatic microscopic injury to dorsal root ganglia (DRG) and trigeminal ganglia (TG) somatosensory neurons, causing neurofilament light chain (NfL) to diffuse into cerebrospinal fluid (CSF) and blood. Data from 260 cynomolgus macaques administered vehicle or AAV9 vectors (intrathecally or intravenously) were analyzed to investigate NfL as a soluble biomarker for monitoring DRG/TG microscopic findings. The incidence of key DRG/TG findings with AAV9 vectors was 78% (maximum histopathology severity, moderate) at 2-12 weeks after the dose.

Facility Design and Health Management Program at the Sinnhuber Aquatic Research Laboratory.

The number of researchers and institutions moving to the utilization of zebrafish for biomedical research continues to increase because of the recognized advantages of this model. Numerous factors should be considered before building a new or retooling an existing facility. Design decisions will directly impact the management and maintenance costs.

The influence of sleep duration and sleep-related symptoms on baseline neurocognitive performance among male and female high school athletes.

Unlabelled: Typically, the effects of sleep duration on cognition are examined in isolation.

Objective: This study examined the effects of restricted sleep and related symptoms on neurocognitive performance.

Method: Baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and postconcussion symptom scale (PCSS) were administered to athletes (N = 7,150) ages 14-17 (M = 15.

The headache electronic diary for children with concussion.

Purpose/objectives: The purposes of the study were to (1) develop a prospective, real time, age-appropriate, and appealing prototype of an electronic headache pain diary for children and (2) evaluate the clinical feasibility and utility of the diary for the assessment and documentation of concussion headache.

Design: A mixed-methods design of qualitative interviews and a quantitative survey was used.

Setting: The setting was a sports medicine concussion clinic.

Neuropsychological assessment of sport-related concussion.

Assessment of concussion can be challenging for medical practitioners given the different factors associated with each individual injury. The use of neuropsychological testing provides an objective method in the evaluation and management of concussion. Over the last 20 years it has become increasingly useful in the realm of sports concussion and has been deemed a cornerstone of concussion management by the Concussion in Sport group at the International Symposia on Concussion in Sport.

Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin peptide.

Unlabelled: Chemically synthesized chlorotoxin (TM601) has been studied as a tumor targeting peptide. In this study, the anti-angiogenic properties of TM601 are reported.

Materials And Methods: In vitro and in vivo models of angiogenesis and tumor growth were used to characterize the anti-angiogenic effects of TM601.

Annexin A2 is a molecular target for TM601, a peptide with tumor-targeting and anti-angiogenic effects.

TM601 is a synthetic form of chlorotoxin, a 36-amino acid peptide derived from the venom of the Israeli scorpion, Leirius quinquestriatus, initially found to specifically bind and inhibit the migration of glioma cells in culture. Subsequent studies demonstrated specific in vitro binding to additional tumor cell lines. Recently, we demonstrated that proliferating human vascular endothelial cells are the only normal cell line tested that exhibits specific binding to TM601.

Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts.

Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in hemorrhagic stroke and seizures. Familial forms of CCM are inherited in an autosomal-dominant fashion, and three CCM genes have been identified. We recently determined that large genomic deletions in the CCM2 gene represent 22% of mutations in a large CCM cohort from the USA.

Distribution of radio-labeled N-Acetyl-L-Cysteine in Sprague-Dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage.

The distribution of radio-labeled N-Acetyl-L-Cysteine (NAC) and its impact on glutathione (GSH) metabolism was studied in Sprague-Dawley rats following single and multiple dosing with NAC by oral gavage. Radioactivity associated with administration of (14)C-NAC distributed to most tissues examined within 1 hour of administration with peak radioactivity levels occurring within 1 hour to 4 hours and for a majority of the tissues examined, radioactivity remained elevated for up to 12 hours or more. Administration of a second dose of 1,200 mg/kg NAC + (14)C-NAC 4 hours after the first increased liver, kidney, skin, thymus, spleen, eye, and serum radioactivity significantly beyond levels achieved following 1 dose.

Effect of method of euthanasia on sperm motility of mature Sprague-Dawley rats.

Euthanasia is one of the most commonly performed procedures in laboratory animal settings. The method of euthanasia may affect experimental results in studies using animals and must be compatible with research objectives including subsequent tissue analyses. Our present study was performed to evaluate the effects of 7 euthanasia methods on sperm motility in mature rats.

Deletions in CCM2 are a common cause of cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including hemorrhagic stroke and seizures. Mutations in the gene KRIT1 are responsible for CCM1, mutations in the gene MGC4607 are responsible for CCM2, and mutations in the gene PDCD10 are responsible for CCM3. DNA sequence analysis of the known CCM genes in a cohort of 63 CCM-affected families showed that a high proportion (40%) of these lacked any identifiable mutation.

Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.

Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including stroke and seizures. Linkage analyses using autosomal dominant families manifesting CCMs have identified three different causative loci on chromosomes 7q21.2 (CCM1), 7p13 (CCM2), and 3q25.

Evaluation of the effect of implanted depleted uranium on male reproductive success, sperm concentration, and sperm velocity.

Depleted uranium (DU) projectiles have been used in battle in Iraq and the Balkans and will continue to be a significant armor-penetrating munition for the US military. As demonstrated in the Persian Gulf War, battle injury from DU projectiles and shrapnel is a possibility, and removal of embedded DU fragments from the body is not always practical because of their location in the body or their small size. Previous studies in rodents have demonstrated that implanted DU mobilizes and translocates to the gonads, and natural uranium may be toxic to spermatazoa and the male reproductive tract.

Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. Mutations in the gene KRIT1 are responsible for type 1 CCM (CCM1). We report that a novel gene, MGC4607, exhibits eight different mutations in nine families with type 2 CCM (CCM2).

Triple immune suppression increases short-term survival of porcine fetal retinal pigment epithelium xenografts.

Purpose: To determine the effect of triple drug immune suppression on RPE xenograft survival in the fetal pig after transplantation into the albino rabbit subretinal space.

Methods: Primary RPE microaggregates (approximately 40,000 RPE cells) were injected into the subretinal space of 24 albino rabbits, with half the rabbits maintained on triple systemic immune suppression. RPE survival was estimated with a DNA probe (porcine DNA repeat element; PRE) against a porcine-specific repetitive chromosomal marker or a RAM-11 antibody against rabbit macrophages.

Mutational analysis of 206 families with cavernous malformations.

Object: A gene contributing to the autosomal-dominant cerebral cavernous malformation (CCM) phenotype, KRIT1 (an acronym for Krev Interaction Trapped 1), has been identified through linkage analysis and mutation screening. The authors collected blood samples from 68 patients with familial CCM and 138 patients with apparently sporadic CCM as well as from their families, in an effort to characterize the prevalence and spectrum of disease-causing sequence variants in the KRIT1 gene.

Methods: The authors used single-strand conformational polymorphism analysis to identify genomic variants in KRIT1, which were sequenced to determine the specific mutation.

Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa.

Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners.