Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process.
Abnormal sleep; apnea; dyssomnia; parasomnia; sleep physiology
contact lens; informed consent
There are few data on the persistence of individual human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) mutations in the absence of selective drug pressure. We studied 313 patients in whom TDR mutations were detected at their first resistance test and who had a subsequent test performed while ART-naive. The rate at which mutations became undetectable was estimated using exponential regression accounting for interval censoring. Most thymidine analogue mutations (TAMs) and T215 revertants (but not T215F/Y) were found to be highly stable, with NNRTI and PI mutations being relatively less persistent. Our estimates are important for informing HIV transmission models.
persistence; transmitted; HIV-1; resistance; mutations
Owing to the low therapeutic index of barbiturates, benzodiazepines (BZDs) became popular in this country and worldwide many decades ago for a wide range of conditions. Because of an increased understanding of pharmacology and physiology, the mechanisms of action of many BZDs are now largely understood, and BZDs of varying potency and duration of action have been developed and marketed. Although BZDs have many therapeutic roles and BZD-mediated effects are typically well tolerated in the general population, side effects and toxicity can result in morbidity and mortality for some patients. The elderly; certain subpopulations of patients with lung, liver, or kidney dysfunction; and patients on other classes of medication are especially prone to toxicity.
This review details the present knowledge about BZD mechanisms of action, drug profiles, clinical actions, and potential side effects. In addition, this review describes numerous types of BZD-mediated central nervous system effects.
For any patient taking a BZD, the prescribing physician must carefully evaluate the risks and benefits, and higher-risk patients require careful considerations. Clinically appropriate use of BZDs requires prudence and the understanding of pharmacology.
Adverse effects; benzodiazepines; central nervous system
Neurofibromatosis type 1 (neurofibromatosis-1), a relatively common single-gene disorder, is caused by a mutation of the NF1 gene that results in a loss of activity or in a nonfunctional neurofibromin protein. Clinical anesthesiologists may find patients with neurofibromatosis-1 challenging because this condition may affect most organ systems and result in a wide variety of presentations and clinical implications. Current neurofibromatosis-1 research studies include genotype-phenotype correlations, investigation of the pathoetiology behind the different clinical manifestations of neurofibromatosis-1, and the search for treatment options for the different features of the disorder. Neurofibromatosis-1–associated complications of the central nervous, respiratory, cardiovascular, musculoskeletal, and gastrointestinal and genitourinary systems all present various degrees of considerations for anesthesiologists. Additionally, neurofibromatosis-1 has dramatic implications for pregnant women.
Anesthesia; café-au-lait macules; NF1 gene; neurofibromatosis type 1
Chronic pain patients often have comorbidities, including social habits such as tobacco abuse, they use to cope with pain states. This study tested the hypothesis that physician activism, communication, and interest in smoking cessation can reduce or eliminate tobacco use.
We developed a survey to evaluate patients' smoking habits and to determine if active physician participation changed these habits.
We surveyed a total of 112 patients. Of the 56 smokers, 59% reported they had previously tried to stop. Smokers initially reported smoking 25.5 cigarettes per day for an average of 18.4 years. After receiving monthly physician messages regarding smoking, 51 of the smokers (91%) reported a reduction. These patients reported an average of 7.2 cigarettes smoked per day. Of the smoking patients, 79% indicated that they were influenced to reduce or stop smoking at the clinic, and 86% recalled that they heard specific statements from their doctor in the clinic. After reducing the number of cigarettes smoked, patients reported breathing better (68%), feeling better (66%), and experiencing less pain (34%).
Physician influence correlated with smoking reduction in this study.
Nicotine; pain management; smoking; tobacco abuse
The use of phenylephrine has been well described as a potential cause of morbidity and mortality. A thorough literature review of phenylephrine use is presented in this article. The use of ketamine and epinephrine with phenylephrine can precipitate an even more potentially lethal and catastrophic syndrome. We present the case of a 21-year-old man with Hodgkin's lymphoma and lupus who experienced an abrupt hypertensive crisis followed by pulseless electrical activity and cardiogenic shock after application of 2.5% phenylephrine-soaked nasal pledgets prior to excision of a large nasopharyngeal tumor. This case report adds to the current literature on the potential dangers of phenylephrine in clinical practice and describes a case of reversible severe left ventricular dysfunction in the setting of excessive pharmacologically induced sympathetic stimulation.
Cardiogenic shock; Hodgkin's lymphoma; lupus; phenylephrine
Somatic mutations at Thr-58 of c-Myc have been detected in Burkitt's lymphoma (BL) tumors and have been shown to affect the transforming potential of the Myc oncoprotein. In addition, the N-terminal domain of c-Myc has been shown to interact with microtubules in vivo, and the binding of c-Myc to α-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with α-tubulin. In addition, we show that wild-type c-Myc–α-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells.
The polymerization of alpha- and beta-tubulin into microtubules results in a complex network of microfibrils that have important structural and functional roles in all eukaryotic cells. In addition, microtubules can interact with a diverse family of polypeptides which are believed to directly promote the assembly of microtubules and to modulate their functional activity. We have demonstrated that the c-Myc oncoprotein interacts in vivo and in vitro with alpha-tubulin and with polymerized microtubules and have defined the binding site to the N-terminal region within the transactivation domain of c-Myc. In addition, we have shown that c-Myc colocalizes with microtubules and remains tightly bound to the microtubule network after detergent extraction of intact cells. These findings suggest a potential role for Myc-tubulin interaction in vivo.
Two hundred fifty clinical isolates of anaerobic bacteria were tested for suceptibility to cefoperazone, cefamandole, cefoxitin, carbenicillin, clindamycin, and chloramphenicol. Anaerobic gram-positive cocci were susceptible to all of the antibiotics tested. Clindamycin was the most active agent against Bacteroides species, followed by chloramphenicol and then cefoxitin. Cefoperazone was less active than cefoxitin and equal in activity to carbenicillin. Cefamandole was the least active antibiotic against Bacteroides. B. distasonis, B. vulgatus, B. thetaiotaomicron, and B. ovatus were more resistant to the antibiotics than B. melaninogenicus, B. oralis, or B. bivius. Clindamycin was the most active agent against Clostridium species, followed by chloramphenicol; the three cephalosporins and carbenicillin were about equal in activity. Clindamycin was the most active antibiotic against Fusobacterium species, followed by chloramphenicol, carbenicillin, and cefoperazone (which were about equally active) and then cefamandole.
The early stages of nuclear differentiation in spermatids of the house cricket are described with regard to the fine structural elements and chemical components which occur. Particular attention is given to the loss of nonhistone protein from the nucleus and its relation to chromatin structure. Granular elements about 25 to 80 mµ in diameter, and fibers about 8 mµ in diameter occur in the earliest spermatid nucleus. The fibers are found in diffuse and condensed chromatin while granules are found only in diffuse material. DNA and histone parallel the chromatin fibers in distribution, while nonhistone protein and RNA parallel the granules in distribution. The granules and most of the nonhistone protein are lost, simultaneously, after the early spermatid stage. The protein loss occurs without detectable change in the structure of chromatin fibers. Chromatin fibers first show a structural change in mid spermiogenesis, when they become thicker and very contorted. Unusually thin fibers (about 5 mµ) also appear in mid spermatid nuclei; they are apparently composed of nonhistone protein and free of DNA and histone.
Latency-associated nuclear antigen (LANA) is encoded by the Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) open reading frame 73. LANA is expressed during latent KSHV infection of cells, including tumor cells, such as primary effusion lymphoma, KS and multicentric Castleman’s disease. Latently infected cells have multiple extrachromosomal copies of covalently closed circular KSHV genomes (episomes) that are stably maintained in proliferating cells. LANA’s best characterized function is that of mediating episome persistence. It does so by binding terminal repeat sequences to the chromosomal matrix, thus ensuring episome replication with each cell division and efficient DNA segregation to daughter nuclei after mitosis. To achieve these functions, LANA associates with different host cell proteins, including chromatin-associated proteins and proteins involved in DNA replication. In addition to episome maintenance, LANA has transcriptional regulatory effects and affects cell growth. LANA exerts these functions through interactions with different cell proteins.
AIDS; HIV; human herpesvirus 8; Kaposi’s sarcoma; lymphoma; viral latency
This study designed and applied accessible yet systematic methods to generate baseline information about the patterns and structure of Canada's neglected tropical disease (NTD) research network; a network that, until recently, was formed and functioned on the periphery of strategic Canadian research funding.
Multiple methods were used to conduct this study, including: (1) a systematic bibliometric procedure to capture archival NTD publications and co-authorship data; (2) a country-level “core-periphery” network analysis to measure and map the structure of Canada's NTD co-authorship network including its size, density, cliques, and centralization; and (3) a statistical analysis to test the correlation between the position of countries in Canada's NTD network (“k-core measure”) and the quantity and quality of research produced.
Over the past sixty years (1950–2010), Canadian researchers have contributed to 1,079 NTD publications, specializing in Leishmania, African sleeping sickness, and leprosy. Of this work, 70% of all first authors and co-authors (n = 4,145) have been Canadian. Since the 1990s, however, a network of international co-authorship activity has been emerging, with representation of researchers from 62 different countries; largely researchers from OECD countries (e.g. United States and United Kingdom) and some non-OECD countries (e.g. Brazil and Iran). Canada has a core-periphery NTD international research structure, with a densely connected group of OECD countries and some African nations, such as Uganda and Kenya. Sitting predominantly on the periphery of this research network is a cluster of 16 non-OECD nations that fall within the lowest GDP percentile of the network.
The publication specialties, composition, and position of NTD researchers within Canada's NTD country network provide evidence that while Canadian researchers currently remain the overall gatekeepers of the NTD research they generate; there is opportunity to leverage existing research collaborations and help advance regions and NTD areas that are currently under-developed.
This study applies co-authorship network analysis to generate baseline information about the patterns and structure of Canada's neglected tropical disease (NTD) publication activity and research network. Researchers, public and private funders, not-for-profit organizations, and policy makers may use the methodology or study findings for targeting, monitoring, and assessing Canada's contribution to a research field that is ready for attention and advancements. Future studies could use the findings to comparatively analyze the emergence of specific NTD research amongst institutional networks or further examine attributes and mechanisms that support and impede Canadian involvement in NTD research production and collaborative North–South research partnerships.
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of invasive surgical site infection (SSI) in the USA. Antimicrobial prophylaxis for SSI typically includes a cephalosporin. Vancomycin is used to provide MRSA coverage, but administration timing is challenging. Linezolid is an attractive agent for SSI prophylaxis, particularly for the prevention of SSI due to MRSA.
We developed a decision-analytic model to evaluate linezolid use for cardiothoracic SSI prophylaxis. A theoretical cohort of 10,000 cardiothoracic surgery patients was followed through 2 stages: 1) occurrence of SSI, and 2) mortality after SSI. All patients were administered cefuroxime, vancomycin, or linezolid between 1–180 minutes prior to surgical incision. SSIs were categorized into three pathogen categories: 1) methicillin-susceptible Gram-positive, 2) methicillin-resistant Gram-positive, and 3) other organisms. The most effective strategy resulted in the fewest SSIs. Assumptions for antibiotic effectiveness, impact of administration time, and pathogens were based on the published literature.
Compared with cefuroxime, there was a 1% increase in the total number of SSIs in the linezolid group (mean SSI increase = 7), while there was a 12% increase in the vancomycin group (mean SSI increase = 86). Linezolid prophylaxis resulted in fewer SSIs due to methicillin-resistant Gram-positive infections (n=108) compared with cefuroxime (n = 200, 46% reduction in the linezolid group) and vancomycin (n = 119, 9% reduction in the linezolid group).
This simulation indicates that linezolid may offer benefits for SSI prophylaxis over existing prophylactic agents, particularly for the prevention of SSI due to Gram-positive methicillin-resistant pathogens.
Surgical site infection; prophylaxis; decision-analytic model; linezolid; vancomycin
Remote telepresence provided by tele-operated robotics represents a new means for obtaining important health information, improving older adults' social and daily functioning and providing peace of mind to family members and caregivers who live remotely. In this study we tested the feasibility of use and acceptance of a remotely controlled robot with video-communication capability in independently living, cognitively intact older adults.
Materials and Methods:
A mobile remotely controlled robot with video-communication ability was placed in the homes of eight seniors. The attitudes and preferences of these volunteers and those of family or friends who communicated with them remotely via the device were assessed through survey instruments.
Overall experiences were consistently positive, with the exception of one user who subsequently progressed to a diagnosis of mild cognitive impairment. Responses from our participants indicated that in general they appreciated the potential of this technology to enhance their physical health and well-being, social connectedness, and ability to live independently at home. Remote users, who were friends or adult children of the participants, were more likely to test the mobility features and had several suggestions for additional useful applications.
Results from the present study showed that a small sample of independently living, cognitively intact older adults and their remote collaterals responded positively to a remote controlled robot with video-communication capabilities. Research is needed to further explore the feasibility and acceptance of this type of technology with a variety of patients and their care contacts.
robotics; tele-operated; aging; technology; video-communication
We show functional-anatomical organization of motion direction in mouse dorsal lateral geniculate nucleus (dLGN) using the first two-photon calcium imaging of dense populations in thalamus. Surprisingly, the superficial 75μm region contains anterior and posterior direction-selective neurons (DSLGNs) intermingled with non-direction-selective neurons, while upward and downward-selective neurons are nearly absent. Unexpectedly, the remaining neurons encode both anterior and posterior directions, forming horizontal motion-axis selectivity. A model of random wiring consistent with these results makes quantitative predictions about the connectivity of direction-selective retinal ganglion cell (DSRGC) inputs to the superficial dLGN. DSLGNs are more sharply tuned than DSRGCs. These results suggest dLGN maintains and sharpens retinal direction selectivity, and integrates opposing DSRGC subtypes in a functional-anatomical region, perhaps forming a novel feature representation for horizontal-axis motion, contrary to dLGN being a simple relay. Furthermore, they support recent conjecture that cortical direction and orientation selectivity emerge in part from a previously undescribed motion-selective retinogeniculate pathway.
MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1–LNP) and let-7a miR encapsulated LNP (miR–LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR–ephrin-A1–LNP) was determined on MPM and NSCLC tumor growth in vitro. miR–ephrin-A1–LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR–ephrin-A1–LNP treatment. Furthermore, the miR–ephrin-A1–LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR–ephrin-A1–LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor.
liposomal nanoparticles; EphA2 receptor; microRNA; ephrin-A1; malignant pleural mesothelioma; non-small-cell lung cancer
We investigated the association between skin rash and plasma creatine kinase (CK) levels in oncology phase I trials.
We analysed data from 295 patients treated at our institution within 25 phase I trials which included CK measurements in the protocol. Trials involved drugs targeting EGFR/HER2, m-TOR, VEGFR, SRC/ABL, aurora kinase, BRAF/MEK, PARP, CDK, A5B1 integrin, as well as oncolytic viruses and vascular disrupting agents.
Creatine kinase measurements were available for 278 patients. The highest levels of plasma CK during the trial were seen among patients with Grade (G) 2/3 rash (median 249 U l−1) compared with G1 (median 81 U l−1) and no rash (median 55 U l−1) (P<0.001). There was a significant reduction in CK after the rash resolved (mean 264.2 vs 100.1; P=0.012) in 25 patients, where serial CK values were available. In vitro exposure of human keratinocytes to EGFR, MEK and a PI3Kinase/m-TOR inhibitor led to the increased expression of CK-brain and not CK-muscle or mitochondrial-CK.
Plasma CK elevation is associated with development of skin rash caused by novel anticancer agents. This should be studied further to characterise different isoforms as this will change the way we report adverse events in oncology phase I clinical trials.
creatine kinase; skin rash; anticancer drug
Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes.
We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process.
Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture.
At 14 days of differentiation, 59±2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway.
Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.
Restoration of weight and nutritional status are key elements in the treatment of anorexia nervosa (AN). This review aims to describe issues related to the caloric requirements needed to gain and maintain weight for short and long-term recovery for AN inpatients and outpatients.
We reviewed the literature in PubMed pertaining to nutritional restoration in AN between 1960–2012. Based on this search, several themes emerged: 1. AN eating behavior; 2. Weight restoration in AN; 3. Role of exercise and metabolism in resistance to weight gain; 3. Medical consequences of weight restoration; 4. Rate of weight gain; 5. Weight maintenance; and 6. Nutrient intake.
A fair amount is known about overall caloric requirements for weight restoration and maintenance for AN. For example, starting at 30–40 kilocalories per kilogram per day (kcal/kg/day) with increases up to 70–100 kcal/kg/day can achieve a weight gain of 1–1.5 kg/week for inpatients. However, little is known about the effects of nutritional deficits on weight gain, or how to meet nutrient requirements for restoration of nutritional status.
This review seeks to draw attention to the need for the development of a foundation of basic nutritional knowledge about AN so that future treatment can be evidenced-based.
Anorexia nervosa; Treatment resistance; Nutritional rehabilitation; Refeeding; Weight restoration; Weight maintenance; Caloric requirements; Refeeding syndrome
Mutations in the GBA gene occur in 7% of patients with Parkinson disease (PD) and are a well-established susceptibility factor for PD, which is characterized by Lewy body disease (LBD) neuropathologic changes (LBDNCs). We sought to determine whether GBA influences risk of dementia with LBDNCs, Alzheimer disease (AD) neuropathologic changes (ADNCs), or both.
We screened the entire GBA coding region for mutations in controls and in subjects with dementia and LBDNCs and no or low levels of ADNCs (pure dementia with Lewy bodies [pDLB]), LBDNCs and high-level ADNCs (LBD-AD), and high-level ADNCs but without LBDNCs (AD).
Among white subjects, pathogenic GBA mutations were identified in 6 of 79 pDLB cases (7.6%), 8 of 222 LBD-AD cases (3.6%), 2 of 243 AD cases (0.8%), and 3 of 381 controls (0.8%). Subjects with pDLB and LBD-AD were more likely to carry mutations than controls (pDLB: odds ratio [OR] = 7.6; 95% confidence interval [CI] = 1.8–31.9; p = 0.006; LBD-AD: OR = 4.6; CI = 1.2–17.6; p = 0.025), but there was no significant difference in frequencies between the AD and control groups (OR = 1.1; CI = 0.2–6.6; p = 0.92). There was a highly significant trend test across groups (χ2(1) = 19.3; p = 1.1 × 10−5), with the likelihood of carrying a GBA mutation increasing in the following direction: control/AD < LBD-AD < pDLB.
GBA is a susceptibility gene across the LBD spectrum, but not in AD, and appears to convey a higher risk for PD and pDLB than for LBD-AD. PD and pDLB might be more similar to one another in genetic determinants and pathophysiology than either disease is to LBD-AD.
After identifying that significant care gaps exist within the management of atrial fibrillation (AF), a patient-focused tool was developed to help patients better assess and manage their AF. This tool aims to provide education and awareness regarding the management of symptoms and stroke risk associated with AF, while engaging patients to identify if their condition is optimally managed and to become involved in their own care. An interdisciplinary group of health care providers and designers worked together in a participatory design approach to develop the tool with input from patients. Usability testing was completed with 22 patients of varying demographics to represent the characteristics of the patient population. The findings from usability testing interviews were used to further improve and develop the tool to improve ease of use. A physician-facing tool was also developed to help to explain the tool and provide a brief summary of the 2012 Canadian Cardiovascular Society atrial fibrillation guidelines. By incorporating patient input and human-centered design with the knowledge, experience, and medical expertise of health care providers, we have used an approach in developing the tool that tries to more effectively meet patients’ needs.
patient education; atrial fibrillation; care gaps; patient care tools; patient self-assessment
One of the recommendations of the 2010 Leon Thal Symposium, organized to develop strategies to prevent Alzheimer’s disease, was to build a global database of longitudinal aging studies. While several databases of longitudinal aging studies exist, none of these are comprehensive or complete. In this paper we review selected databases of longitudinal aging studies. We make recommendations on future steps to create a comprehensive database. Additionally, we discuss issues related to data harmonization.
This study examines differences in computer related self-efficacy and anxiety in subgroups of older adults, and changes in those measures following exposure to a systematic training program and subsequent computer use.
Participants were volunteers in the Intelligent Systems for Assessment of Aging Changes Study (ISAAC) carried out by the Oregon Center for Aging and Technology. Participants were administered two questionnaires prior to training and again one year later, related to computer self-efficacy and anxiety. Continuous recording of computer use was also assessed for a subset of participants.
Baseline comparisons by gender, age, education, living arrangement, and computer proficiency, but not cognitive status, yielded significant differences in confidence and anxiety related to specific aspects of computer use. At one-year follow-up, participants reported less anxiety and greater confidence. However, the benefits of training and exposure varied by group and task. Comparisons based on cognitive status showed that the cognitively intact participants benefited more from training and/or experience with computers than did participants with Mild Cognitive Impairment (MCI), who after one year continued to report less confidence and more anxiety regarding certain aspects of computer use.
After one year of consistent computer use, cognitively intact participants in this study reported reduced levels of anxiety and increased self-confidence in their ability to perform specific computer tasks. Participants with MCI at baseline were less likely to demonstrate increased efficacy or confidence than their cognitively intact counterparts.
Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNPs) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes.
Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000 observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates.
We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined.
These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies.
These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.