PRKDC mutations in a SCID patient with profound neurological abnormalities

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs; encoded byPRKDC) functions in DNA non-homologous end-joining (NHEJ), themajor DNA double strand break (DSB) rejoining pathway. NHEJ also functions duringlymphocyte development, joining V(D)J recombination intermediates during antigenreceptor gene assembly. Here, we describe a patient with compound heterozygousmutations in PRKDC, low DNA-PKcs expression, barely detectableDNA-PK kinase activity, and impaired DSB repair. In a heterologous expression system,we found that one of the PRKDC mutations inactivated DNA-PKcs, whilethe other resulted in dramatically diminished but detectable residual function. Thepatient suffered SCID with reduced or absent T and B cells, as predicted fromPRKDC-deficient animal models. Unexpectedly, the patient was alsodysmorphic; showed severe growth failure, microcephaly, and seizures; and hadprofound, globally impaired neurological function. MRI scans revealedmicrocephaly-associated cortical and hippocampal dysplasia and progressive atrophyover 2 years of life. These neurological features were markedly more severe thanthose observed in patients with deficiencies in other NHEJ proteins. Although loss ofDNA-PKcs in mice, dogs, and horses was previously shown not to impair neuronaldevelopment, our findings demonstrate a stringent requirement for DNA-PKcs duringhuman neuronal development and suggest that high DNA-PK protein expression isrequired to sustain efficient pre- and postnatal neurogenesis.     

An Evaluation of a Direct Instructions Flashcard System on the Acquisition and Generalization of Numerals, Shapes, and Colors for Preschool-Aged Students with Developmental Delays

The purpose of this study was to evaluate the effectiveness of the DI Flashcard system for teaching preliminary mathematic skills to three preschool students. The participants attended a self-contained special education preschool. All three participants’ eligibility category was “developmentally delayed”. A concurrent multiple baseline design across three sets (colors, shapes, and numerals) was use to evaluate the effectiveness of the DI flashcard system. The results indicated that all three participants showed an increase in their performance when DI flashcards were in effect. However, the amount of improvement varied for each participant. The importance of employing evidence-based procedures to teach skills to preschool students with developmental delays was outlined.     

Mechanical Thrombectomy for Acute Ischemic Stroke: A Case Study Using the Penumbra Stroke System

Over recent years, there have been dramatic advances in the ability to treat an acute ischemic stroke. Thrombolysis with intravenous recombinant tissue plasminogen activator can now be performed up to 4.5 hr after stroke onset in certain circumstances, and new mechanical thrombectomy devices allow intervention up to and beyond 8 hr in some instances. The Penumbra Stroke System (Penumbra Inc., Alameda, CA), one of these mechanical thrombectomy devices, uses a series of catheters to aspirate thrombus from occluded cerebral arteries and thus restore flow to the adjacent ischemic brain.This case study highlights the clinical and procedural issues involved in the treatment and postprocedural care of a patient with an acute ischemic stroke treated with the Penumbra Stroke System.     

Increased Mortality in a Colony of Zebra Finches Exposed to Continuous Light

Over a 1-mo period, increased morbidity and mortality occurred in a flock of zebra finches (Taeniopygia guttata). Complete postmortem examination was performed on 6 of the affected birds, 4 of which subsequently were diagnosed with the avian gastric yeast previously known as megabacteriosis (Macrorhabdus ornithogaster). The remaining 2 birds were diagnosed with a cloacal abscess and with large bowel perforation and peritonitis. All the birds had been prophylactically treated with amphotericin B for megabacteria 2 mo previously. An environmental assessment revealed that the light cycle had been altered, and the birds were being exposed to constant light. With correction of the light cycle, the health of the birds improved dramatically. The remaining birds were treated again with amphotericin B, and baseline mortality returned to normal. The birds in this report show several similarities to previous reports of sleep deprivation syndrome in mammals.Over a 1-mo period (from late April to late May 2011), a marked increase in morbidity and mortality was noted in a flock of zebra finches (Taeniopygia guttata) at our facility (University of Washington). These birds were involved in a project studying the neural mechanisms of vocal learning. The finches were obtained from Magnolia Bird Farm (Anaheim, CA). In March 2011, a shipment of 50 male birds arrived and was moved into a new space with 2 rooms. One room housed breeding birds in cages containing breeding pairs and offspring; the other room, into which these new arrivals were placed, housed adult male birds in cages of 4 to 9 birds.Birds in the room containing the adult nonbreeders were affected exclusively. Clinical signs consisted of puffed and ruffled feathers, lethargy, increased respiratory effort, and feather loss. These signs were noted in birds that had not undergone experimental manipulation. Several of the birds that died or were euthanized after becoming sick and lethargic were necropsied. Findings on postmortem examination for the majority of cases included emaciated body condition, necrotizing enteritis and colitis and, in individual cases, included bowel perforation and peritonitis and severe pyogranulomatous abscessation. Megabacteriosis (avian gastric yeast; Macrorhabdus ornithogaster) was diagnosed histologically in 4 of the 6 birds evaluated. A light meter was placed in the housing room; results showed that the dark period of the light cycle was absent. The light cycle was corrected, and morbidity and mortality decreased dramatically.     

ADULTS MOURNING SUICIDE: SELF-REPORTED CONCERNS ABOUT BEREAVEMENT,NEEDS FOR ASSISTANCE,AND HELP-SEEKING BEHAVIOR

This study empirically characterized the experiences of 227 adult next-of-kin as they mourned suicides that had occurred in New York City during 1997. Next-of-kin reported psychosocial problems including family difficulties, comorbid stressors, psychiatric symptomatology, and unresolved bereavement. Professional intervention was the most frequently reported need and the most frequently reported type of desired help. In terms of actual receipt of assistance, participants reported having received help from families, friends, and communities as well as from professionals. Although some next-of-kin had not sought help because they felt able to cope without assistance, others encountered barriers to receiving desired help. These findings warrant increased and sustained community outreach to this population. Recommendations include public education regarding de-stigmatization of suicide and the needs of the suicidally bereaved, enhancement of internal and external coping supports, facilitation of access to both professional and community help, and better coordinated and more culturally appropriate services.     

Coincident Tick Infestations in the Nostrils of Wild Chimpanzees and a Human in Uganda

Ticks in the nostrils of humans visiting equatorial African forests have been reported sporadically for decades, but their taxonomy and natural history have remained obscure. We report human infestation with a nostril tick in Kibale National Park, Uganda, coincident with infestation of chimpanzees in the same location with nostril ticks, as shown by high-resolution digital photography. The human-derived nostril tick was identified morphologically and genetically as a nymph of the genus Amblyomma, but the mitochondrial 12S ribosomal RNA or the nuclear intergenic transcribed spacer 2 DNA sequences of the specimen were not represented in GenBank. These ticks may represent a previously uncharacterized species that is adapted to infesting chimpanzee nostrils as a defense against grooming. Ticks that feed upon apes and humans may facilitate cross-species transmission of pathogens, and the risk of exposure is likely elevated for persons who frequent ape habitats.     

The comparison of two negative‐pressure wound therapy systems in a porcine model of wound healing

The purpose of this study was to compare two negative‐pressure wound healing systems (NPWT), ?75 mmHg with a silicone‐coated (SC) dressing and ?125 mmHg with polyurethane foam dressing (standard of care). In addition, this study compared the effects of two different dressing interfaces, SC dressing and gauze, with ?75 mmHg pressure. For both comparisons, two groups of five pigs were evaluated over a 21‐day time course. Two excisional wounds were made on each animal and NPWT dressings were applied. A canvas saddle was constructed to hold the NPWT device so the animal had free range of the pen. Dressings were changed twice a week and wound measurements were taken. Specimens for histology and gene expression analyses were taken on day 7 and 21. These data show that there is increased expression in a few genes associated with remodeling and inflammatory processes in the NPWT‐125 with polyurethane foam as compared with the NPWT‐75 with SC dressing. These two systems, however, are equivalent with respect to wound healing, histology, and gene expression over 21 days of healing. Further, we demonstrate that there is no difference in measure of healing between the SC dressing and a basic gauze dressing.