Summary
Background Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)‐ and chemical‐induced DNA ...damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun‐exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER‐defective form of XP of seven complementation groups, designated XP‐A to XP‐G. These complementation groups correspond to different proteins involved in the NER process. XP‐A classically includes some of the most severely affected patients.
Objectives We describe a 61‐year‐old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene.
Methods Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing.
Results Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP‐A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A→G at the eighth nucleotide of intron 4 causing aberrant splicing and a nonfunctional truncated XP‐A protein. However, a small amount of normally spliced mRNA was detected at <5% the level in normal cells.
Conclusions The small amount of normally spliced mRNA detected may be sufficient to explain the relatively mild clinical features in our patient.
Antiplatelet medication use continues to rise in an aging population, and these agents can have a deleterious effect for patients with traumatic intracranial hemorrhage (tICH). The purpose of the ...current investigation is to assess the safety and efficacy of using platelet reactivity testing (PRT) to direct platelet transfusion for tICH patients.
A Level I trauma center adopted a targeted platelet transfusion guideline using PRT to determine whether platelets were inhibited by an antiplatelet medication (aspirin or P2Y12 inhibitors). Non-inhibited patients were monitored without platelet transfusion, regardless of severity of the head injury. The guideline was analyzed retrospectively to evaluate patient outcomes during the study period (June 2014–December 2016). All patients sustained blunt tICH and received a PRT for known or suspected antiplatelet medication use. Differences were assessed with Kruskal-Wallis and Fisher’s Exact tests.
166 patients met study inclusion criteria. PRT results indicated that 48 patients (29%) were not inhibited by an antiplatelet medication, and 92% of those patients (n = 44) were spared platelet transfusion. Seven percent (n = 11) of all patients had a clinically significant progression of the head bleed, but this did not differ by inhibition or transfusion status. Implementation of this guideline reduced platelet transfusions by an estimated 30–50% and associated healthcare costs by 42%.
A targeted platelet transfusion guideline using PRT reduced platelet usage for patients with tICH. If appropriately tested, results suggest that not all tICH patients taking or suspected of taking antiplatelet drugs need platelet transfusion. Platelet reactivity testing can significantly reduce healthcare costs and resource usage.
Effective Hospital-Wide Education in Hemorrhage Control Hegvik, James R., MD; Spilman, Sarah K., MA; Olson, Sherry D., RN, BSN ...
Journal of the American College of Surgeons,
05/2017, Letnik:
224, Številka:
5
Journal Article
Recenzirano
Background Uncontrolled hemorrhage is the leading cause of potentially preventable traumatic death. Bleeding victims must receive immediate medical attention to save lives, and the first opportunity ...to control bleeding after trauma often comes from bystanders. Educating the general public is important for improving outcomes for hemorrhaging victims, and it is imperative for all people, including those with no clinical training, to have the knowledge to respond until trained medical specialists arrive. Study Design An 8-minute educational module was deployed to all hospital employees and included information on the location and contents of hemorrhage control bags in the hospital and how to use the materials in the bags to respond to uncontrolled hemorrhage. A pre-post questionnaire was administered with the module to evaluate effectiveness. McNemar tests were used to compare the responses and evaluate effectiveness of the education. Results Eighty-four percent of eligible employees (n = 4,845) completed the module and all items on the questionnaires. Three-quarters of respondents provided direct or ancillary care to patients, and one-quarter worked in nonclinical roles. On average, 57% of questions were answered correctly in the pre-questionnaire and 98% were answered correctly in the post-questionnaire. The module was effective for all employees regardless of clinical training. Conclusions There is currently no succinct hemorrhage control education available that can be deployed across a large workplace environment. Results demonstrate that the brief learning module was effective in educating all employees in the basics of hemorrhage control. The module could be deployed in clinical and nonclinical settings.
The upgraded DØ detector Abazov, V.M.; Alves, G.A.; Askew, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2006, Letnik:
565, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The DØ experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements ...to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid-argon calorimeters and central muon detector, remaining from Run I, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DØ.
The DONUT experiment has analyzed 203 neutrino interactions recorded in nuclear emulsion targets. A decay search has found evidence of four tau neutrino interactions with an estimated background of ...0.34 events. This number is consistent with the Standard Model expectation.
Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice ...(both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
Objective: Injured all-terrain vehicle (ATV) riders contribute to the national trauma burden. The importance of helmet use on injury severity and outcomes in ATV drivers versus passengers that ...receive care is unknown along with the association of payor status and helmet use in this population. An investigation of whether helmet use protects ATV drivers and passengers resulting in less severe injuries, better outcomes, and a lower cost burden to society is to be conducted. Methods: A retrospective review of injured ATV riders in the National Trauma Data Bank from the United States for 2000-2004. Results: Helmet use status was recorded for 5897 drivers and 836 passengers; 83 percent of drivers were male; 41 percent of passengers were female. Helmets were not widely worn (35% of drivers, 19% of passengers, p < .0001) and were less common among female than male drivers who crashed and received care (26% versus 37%, p < .0001). Drivers were older than passengers (p < .0001) and had more thorax, spine, and upper extremity injuries (p < .05). Helmets protected drivers and passengers: decreased head injuries, face injuries, injury severity, and mortality with increased likelihood of being discharged home rather than elsewhere (p < .0001). Personal insurance was more frequent in helmeted riders:
66 percent versus 55 percent of helmeted versus nonhelmeted drivers (p < .0001) and 69 percent versus 55 percent of helmeted versus nonhelmeted passengers (p = .03). Conclusions: Helmets are frequently not worn by ATV riders. Helmets protect ATV drivers and passengers and decrease societal costs associated with ATV crashes.
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