Insomnia is a common symptom of posttraumatic stress disorder (PTSD) that is resistant to first-line cognitive behavioral interventions. However, research suggests that, among individuals with PTSD, ...self-reported sleep impairment is typically more severe than what is objectively observed, a phenomenon termed sleep state misperception. Relatively little research has examined which individuals with PTSD are most likely to exhibit sleep state misperception. This study explored clinical predictors of sleep state misperception in a sample of 43 women with PTSD and clinically significant sleep impairment.
During a baseline assessment, participants' PTSD symptoms were assessed using a clinical interview and their sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI). Objective sleep, self-reported sleep, and PTSD symptoms were then assessed over a 1-week period using actigraphy and daily diaries.
Consistent with previous research, women in the study exhibited total sleep time (TST), sleep efficiency (SE), and sleep onset latency (SOL) sleep state misperception. For TST and SE, but not SOL, discrepancies between actigraphy and the PSQI were associated with each clinician-rated PTSD symptom cluster, whereas discrepancies between actigraphy and daily diary were only associated with clinician-rated reexperiencing symptoms. The only self-reported PTSD symptom that was uniquely associated with sleep state misperception was nightmares. This association was no longer significant after controlling for sleep-related anxiety.
Results suggest that women with more severe reexperiencing symptoms of PTSD, particularly nightmares, may be more likely to exhibit TST and SE sleep state misperception, perhaps due to associated sleep-related anxiety.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective To determine the population-based inpatient disease burden of parainfluenza virus in children <5 years of age. Study design The New Vaccine Surveillance Network (NVSN) enrolled children <5 ...years of age who were hospitalized with febrile or acute respiratory illnesses. Surveillance hospitals admitted >95% of all hospitalized children from each county. Combined nasal turbinate/throat swabs were tested for parainfluenza virus (PIV), respiratory syncytial virus, and influenza virus with culture and reverse-transcription-polymerase chain reaction. Both parental interviews and medical chart reviews were conducted. Age-specific population-based hospitalization rates were calculated. Results From October 2000 through September 2004, 2798 children were enrolled. A total of 191 PIVs were identified from 189 children (6.8% of enrolled: 73 PIV type 1, 23 PIV type 2, and 95 PIV type 3), compared with 521 respiratory syncytial viruses and 159 influenza viruses. Mean PIV hospitalization rates were 3.01, 1.73, 1.53, 0.39, and 1.02 per 1000 children per year for ages 0 to 5 months, 6 to 11 months, 12 to 23 months, 24 to 59 months, and 0 to 59 months, respectively. Conclusions PIV accounted for 6.8% of all hospitalizations for fever, acute respiratory illnesses, or both in children <5 years of age. The pediatric PIV inpatient burden is substantial and highlights the need to find an effective vaccine candidate.
Human metapneumovirus (HMPV) was identified in 2001 as a cause of respiratory infection. In this study at three U.S. surveillance centers, HPMV was found in 6 to 7% of children (<5 years old) ...admitted to the hospital or seen in outpatient clinics and emergency departments.
Human metapneumovirus (HMPV), a paramyxovirus discovered in 2001, is associated with acute respiratory illness among infants and children worldwide.
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In addition, HMPV causes acute respiratory illness and results in hospitalization among older adults and persons with underlying chronic conditions, including asthma, cancer, and chronic obstructive pulmonary disease.
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However, the seasonality of HMPV disease and its overall burden in hospitalizations and outpatient visits among young children remain poorly defined. Previously published studies have been limited by their retrospective nature,
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the use of data collected from convenience samples over relatively short periods, and the absence of asymptomatic controls.
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Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency ...of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF).
We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.
This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We describe a novel selective inhibitor ...of Bcr-Abl, AMN107 (IC
50 < 30 nM), which is significantly more potent than imatinib, and active against a number of imatinib-resistant Bcr-Abl mutants. Crystallographic analysis of Abl-AMN107 complexes provides a structural explanation for the differential activity of AMN107 and imatinib against imatinib-resistant Bcr-Abl. Consistent with its in vitro and pharmacokinetic profile, AMN107 prolonged survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolonged survival in imatinib-resistant CML mouse models. AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL.
Objective: Insomnia, characterized by difficulty falling and staying asleep, is a common and debilitating symptom of posttraumatic stress disorder (PTSD) that is resistant to first-line, ...trauma-focused therapies. Previous research has found that sleep-directed hypnosis improves subjective sleep quality, particularly sleep onset latency, in women with PTSD. However, it cannot be assumed that improvements in subjective sleep reports correspond with objectively measured sleep improvements, because research has indicated a lack of agreement across these measures. The current study examined the effects of sleep-directed hypnosis plus cognitive processing therapy (hypCPT) on objective indices of sleep quality measured with actigraphy. Method: Forty-five women with PTSD were randomized to receive sleep-directed hypCPT or sleep and psychiatric symptom monitoring plus CPT (ssmCPT). Pre- and posttreatment, participants completed 1 week of daily actigraphy assessments of nocturnal sleep onset latency, waking after sleep onset, and total sleep time. Results: Overall improvement in objective sleep indices was not observed. Despite this, at posttreatment, treatment completers receiving hypCPT took significantly less time to fall asleep than did women receiving ssmCPT. Conclusions: More research is needed to understand and reduce the discrepancy between subjectively and objectively assessed sleep impairments in PTSD. Nevertheless, results indicate that adding sleep-directed hypnosis to trauma-focused therapy may be of some use for individuals with PTSD-related insomnia.
Clinical Impact Statement
This study examined the effects of sleep-directed hypnosis and cognitive processing therapy on objectively assessed sleep quality in women with posttraumatic stress disorder. In contrast to the severe insomnia symptoms they reported, participants exhibited relatively normal objective sleep patterns. Despite this, compared to controls, women receiving sleep-directed hypnosis tended to take less time to fall asleep at the beginning of the night. This suggests that sleep-directed hypnosis may be a promising add-on to existing trauma-focused therapies.
Infections caused by carbapenemase‐producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients ...are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo‐β‐lactamase (MBL)‐producing Gram‐negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer β‐lactamase inhibitors such as avibactam have well‐established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL‐producing organisms. Conversely, aztreonam has activity against MBL‐producing organisms but is often inactivated by other co‐existing β‐lactamases. Here, we report four cases of invasive MBL‐CPE infections in transplant recipients caused by IMP‐4‐producing Enterobacter cloacae who were successfully treated with a new, mechanism‐driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high‐risk patients with CPE infection, with reduced drug interactions and toxicity.
Background. Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease ...have not been established. Methods. We conducted population-based prospective surveillance for 2 years in 2 US counties of HMPV infection among children <5 years old who were hospitalized with ARI or fever. Nasal and throat specimens obtained with swabs were tested for HMPV by real-time reverse-transcription polymerase chain reaction and genotyped. Results. Forty-two (3.8%) of 1104 children tested positive for HMPV. The overall annual rate of HMPVassociated hospitalizations per 1000 children <5 years old was 1.2 (95% confidence interval CI, 0.9–1.6). This rate was highest among infants 0–5 months old (4.9 per 1000 95% CI, 2.9–7.2), followed by children 6–11 months old (2.9 per 1000 95% CI, 1.4–4.7). The annual rate of hospitalization for HMPV infection was less than that for respiratory syncytial virus infection but similar to that for influenza and parainfluenza virus 3 infection in all age groups. The mean age of children hospitalized with HMPV infection was 6 months. Bronchiolitis, pneumonia, and asthma were the most common diagnoses among children with HMPV infection. All 4 HMPV subgroups were detected during both years at both sites. HPMV infection was most prominent from March through May. Conclusion. HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza virus and parainfluenza virus 3.
Nonsmall cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. While mutations in Kras and overexpression of Myc are commonly found in patients, the role of altered lipid metabolism ...in lung cancer and its interplay with oncogenic Myc is poorly understood. Here we use a transgenic mouse model of Kras-driven lung adenocarcinoma with reversible activation of Myc combined with surface analysis lipid profiling of lung tumors and transcriptomics to study the effect of Myc activity on cholesterol homeostasis. Our findings reveal that the activation of Myc leads to the accumulation of cholesteryl esters (CEs) stored in lipid droplets. Subsequent Myc deactivation leads to further increases in CEs, in contrast to tumors in which Myc was never activated. Gene expression analysis linked cholesterol transport and storage pathways to Myc activity. Our results suggest that increased Myc activity is associated with increased cholesterol influx, reduced efflux, and accumulation of CE-rich lipid droplets in lung tumors. Targeting cholesterol homeostasis is proposed as a promising avenue to explore for novel treatments of lung cancer, with diagnostic and stratification potential in human NSCLC.
Objectives
To compare the results of Gleason Grade Group (GGG) classification following central pathology review with previous local pathology assessment, and to examine the difference between using ...overall and worst GGG in a large patient cohort treated with radiotherapy and short‐course hormone therapy.
Patients and Methods
Patients with low‐ to high‐risk localized prostate cancer were randomized into the multicentre CHHiP fractionation trial between 2002 and 2011. Patients received short‐course hormone therapy (≤6 month) and radical intensity‐modulated radiotherapy (IMRT). Of 2749 consented patients, 1875 had adequate diagnostic biopsy tissue for blinded central pathology review. The median follow‐up was 9.3 years. Agreement between local pathology and central pathology‐derived GGG and between central pathology‐derived overall and worst GGG was assessed using kappa (κ) statistics. Multivariate Cox regression and Kaplan–Meier methods were used to compare the biochemical/clinical failure (BCF) and distant metastases (DM) outcomes of patients with GGG 1–5.
Results
There was poor agreement between local pathology‐ and central pathology‐derived GGG (κ = 0.19) but good agreement between overall and worst GGG on central pathology review (κ = 0.89). Central pathology‐derived GGG stratified BCF and DM outcomes better than local pathology, while overall and worst GGG on central pathology review performed similarly. GGG 3 segregated with GGG 4 for BCF, with BCF‐free rates of 90%, 82%, 74%, 71% and 58% for GGGs 1–5, respectively, at 8 years when assessed using overall GGG. There was a progressive decrease in DM‐free rates from 98%, 96%, 92%, 88% and 83% for GGGs 1–5, respectively, at 8 years with overall GGG. Patients (n = 57) who were upgraded from GGG 2–3 using worst GS had BCF‐free and DM‐free rates of 74% and 92% at 8 years. CHHiP eligibility criteria limit the interpretation of these results.
Conclusion
Contemporary review of International Society of Urological Pathology GGG successfully stratified patients treated with short‐course hormone therapy and IMRT with regard to both BCF‐free and DM‐free outcomes. Patients upgraded from GGG 2 to GGG 3 using worst biopsy GS segregate with GGG 3 on long‐term follow‐up. We recommend that both overall and worst GS be used to derive GGG.
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