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Lung cancer screening (LCS) with low-dose radiation computed tomography (LDCT) reduces mortality and is recommended for high-risk current and former smokers. Several potential harms associated with LCS have been identified, including the potential for psychological burden. To summarize the current state of the scientific knowledge on psychological burden associated with LCS, we performed a systematic search of the contemporary quantitative and qualitative research literature. We included randomized controlled trials and cohort studies that evaluated the effect of LCS with LDCT on psychological burden and health-related quality of life assessed using validated and nonvalidated measures. PubMed, CINAHL, PsychINFO, and Scopus were searched for English language articles published between 2004 and January 2015. Data abstraction and quality assessment were conducted by 2 independent reviewers. Thirteen studies were included that met our inclusion criteria. Overall, results were variable with some studies reporting worse psychological burden for patients with indeterminate results at prescreening, after screening, and at short-term follow-up (<6 months after screen). These adverse effects diminished or resolved at long-term follow-up (> 6 months after screen). LCS might be associated with short-term adverse psychological burden, particularly after a false positive result. However, these adverse effects diminished over time. The amount of current evidence is small, with limitations in study design and use of outcome measures. More high-quality research is needed to determine the frequency, duration, and overall magnitude of LCS-related psychological burden in nonclinical trial settings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obesity is a source of major morbidity and mortality and is a growing concern worldwide. Maternal obesity is associated with increased maternal and fetal risks during pregnancy. Bariatric surgery has emerged as one of the most sustainable treatments for severe obesity and its comorbidities. Patients who have undergone bariatric surgery often experience drastic improvements in hypertension and diabetes. It is not surprising, therefore, that the incidence of bariatric surgery is increasing, particularly in women of childbearing age. In fact, many women undergoing bariatric surgery plan to become pregnant in the future. Bariatric surgery may have a beneficial effect on rates of fetal macrosomia, gestational diabetes, hypertension, and preeclampsia. Conversely, studies have showed that bariatric surgery may increase the risk of small for gestational age infants and preterm birth. Given its rising incidence, it is important that physicians be able to thoroughly and accurately counsel and treat patients who plan to, or do, become pregnant after bariatric surgery.

Background: Extremely preterm or extremely low birth weight (ELBW) children who are non-disabled and otherwise healthy are at risk of neurodevelopmental impairments. Further understanding of these impairments is needed before commencement of formal education to optimise participation levels at a critical time point for these children., Aims: To explore motor co-ordination, postural stability, limb strength and behaviour of non-disabled four to five year old children with a history of extreme prematurity or ELBW., Study Design: Prospective-descriptive-cohort-study., Subjects: 50 children born at less than 28 weeks gestation or who had a birth weight less than 1000g with minimal/mild motor impairments and no significant neurological/cognitive impairments., Outcome Measures: Movement Assessment Battery for Children second-edition (MABC-2), single leg stance test (SLS), lateral reach test, standing long jump test and Child Behaviour Checklist for preschool children (CBCL)., Results: The mean percentile rank of the extremely preterm or ELBW sample on MABC-2 was 31% (SD 23%). SLS right (mean ± SD; 4.6 ± 2.5s) and lateral reach to the right (10.0 ± 3.9 cm) were slightly stronger than SLS left (4.4 ± 3.3s) and lateral reach left (9.9 ± 3.5 cm). The average for standing long jump was 71.6 cm (SD 21.0 cm). All participants were classified as 'normal' on CBCL syndrome scale scores, internalizing and externalizing syndrome T scores and total problem T score., Conclusions: This sample of non-disabled extremely preterm or ELBW children performed in the lower range of normal. These children continue to be at risk of impairments, therefore, ongoing monitoring and tailored intervention may optimise development., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Historical use of fasting at midnight before anesthesia and surgery has been based on tradition instead of evidence. Research has challenged this practice and determined consuming clear liquids (e.g., water, apple juice, black tea, black coffee) 2-3 hours before surgery does not increase gastric residual volume or risk for aspiration. Liberal fasting guidelines have been published to support this research; however, there continues to be a disparity between practice and evidence. Metabolic alterations occur in the starved state and current available evidence suggests the use of a carbohydrate-rich clear liquid beverage to stimulate the fed state. The fed state is characterized by insulin secretion that stimulates the storage of macronutrients for fuel and promotes protein synthesis. Implementing this practice may decrease insulin resistance and support immune function. Allowing the patient to consume carbohydrate-rich clear liquid beverages may reduce postoperative nausea and vomiting and improve patient reports of anxiety, hunger, and thirst. This article evaluates the evidence for providing clear liquids and carbohydrate-rich clear liquid beverages to healthy adults undergoing surgery to optimize postoperative recovery.

The mechanisms that underlie the selection of an inhibitory GABAergic axon's postsynaptic targets and the formation of the first contacts are currently unknown. To determine whether expression of GABAA receptors (GABAA Rs) themselves--the essential functional postsynaptic components of GABAergic synapses--can be sufficient to initiate formation of synaptic contacts, a novel co-culture system was devised. In this system, the presynaptic GABAergic axons originated from embryonic rat basal ganglia medium spiny neurones, whereas their most prevalent postsynaptic targets, i.e., α1/β2/γ2-GABAA Rs, were expressed constitutively in a stably transfected human embryonic kidney 293 (HEK293) cell line. The first synapse-like contacts in these co-cultures were detected by colocalization of presynaptic and postsynaptic markers within 2 h. The number of contacts reached a plateau at 24 h. These contacts were stable, as assessed by live cell imaging; they were active, as determined by uptake of a fluorescently labelled synaptotagmin vesicle-luminal domain-specific antibody; and they supported spontaneous and action potential-driven postsynaptic GABAergic currents. Ultrastructural analysis confirmed the presence of characteristics typical of active synapses. Synapse formation was not observed with control or N-methyl-d-aspartate receptor-expressing HEK293 cells. A prominent increase in synapse formation and strength was observed when neuroligin-2 was co-expressed with GABAA Rs, suggesting a cooperative relationship between these proteins. Thus, in addition to fulfilling an essential functional role, postsynaptic GABAA Rs can promote the adhesion of inhibitory axons and the development of functional synapses., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Functional hemodynamic indicators (systolic pressure variation [SPV and SPV%] and pulse pressure variation [PPV%]) are sensitive and specific indicators of fluid responsiveness. It was unknown if these indicators could be accurately measured directly from the bedside monitor., Objective: Determine the accuracy of SPV, SPV%, and PPV% measurements by using a stop-cursor method compared with a digitized analog strip (gold standard)., Methods: A prospective observational study using a convenience sample of 30 adult patients in a medical-surgical intensive care unit who were receiving mechanical ventilation and had no spontaneous breaths during 3 sequential ventilator breaths and had an optimized arterial catheter. The peak and nadir arterial pressure values for a ventilator cycle were simultaneously obtained by using the stop-cursor method on the bedside monitor and a hardcopy strip. The indicators were averaged over 3 breaths, and the difference between methods was calculated., Results: Data were analyzed from 29 patients (1 patient excluded) on assist control ventilation (mean [SD] for tidal volume, 7.5 [2] mL/kg; positive end-expiratory pressure, 7 [4] cm H2O). For SPV, the mean bias was 0.4 (SD, 0.9) mm Hg (95% limits of agreement [LOA], -1.4 to 2.2 mm Hg); for SPV%, 0.3 (SD, 0.9; 95% LOA, -1.5% to 2.1%); for PPV%, 1.0 (SD, 3.3; 95% LOA, -5.5% to 7.5%). In only 1 case (PPV%) was there disagreement on fluid response characterization., Conclusions: Statistically significant small differences in SPV and SPV% were detected. The differences in SPV, SPV%, and PPV% were not clinically significant, suggesting that functional hemodynamic indicators can be obtained accurately with the stop-cursor method.

Activated protein C (APC) has potent anticoagulant and anti-inflammatory properties that limit clot formation, inhibit apoptosis, and protect vascular endothelial cell barrier integrity. In this study, the role of N-linked glycans in modulating APC endothelial cytoprotective signaling via endothelial cell protein C receptor/protease-activated receptor 1 (PAR1) was investigated. Enzymatic digestion of APC N-linked glycans (PNG-APC) decreased the APC concentration required to achieve half-maximal inhibition of thrombin-induced endothelial cell barrier permeability by 6-fold. Furthermore, PNG-APC exhibited increased protection against staurosporine-induced endothelial cell apoptosis when compared with untreated APC. To investigate the specific N-linked glycans responsible, recombinant APC variants were generated in which each N-linked glycan attachment site was eliminated. Of these, APC-N329Q was up to 5-fold more efficient in protecting endothelial barrier function when compared with wild type APC. Based on these findings, an APC variant (APC-L38D/N329Q) was generated with minimal anticoagulant activity, but 5-fold enhanced endothelial barrier protective function and 30-fold improved anti-apoptotic function when compared with wild type APC. These data highlight the previously unidentified role of APC N-linked glycosylation in modulating endothelial cell protein C receptor-dependent cytoprotective signaling via PAR1. Furthermore, our data suggest that plasma β-protein C, characterized by aberrant N-linked glycosylation at Asn-329, may be particularly important for maintenance of APC cytoprotective functions in vivo.

Objective: Autosomal dominant parkinsonism, hypoventilation, depression and severe weight loss (Perry syndrome) is an early-onset rapidly progressive disease. At autopsy, previous studies have found severe neuronal loss in the substantia nigra without Lewy bodies. Transactive response DNA-binding protein of 43 kDa (TDP-43) has recently been identified as a major ubiquitinated constituent of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. This study reports clinical, genetic and neuropathologic investigations of Perry syndrome., Methods: Clinical data and autopsy brain tissue samples were collected from eight patients from four genealogically unrelated kindreds with Perry syndrome. Brain tissue was studied with immunohistochemistry and biochemistry for TDP-43. Patients were screened for mutations in the progranulin (GRN) and TDP-43 (TARDBP) genes., Results: The mean age at onset was 47 years (range 40-56), and the mean age at death was 52 years (range 44-64). In all patients, we identified TDP-43-positive neuronal inclusions, dystrophic neurites and axonal spheroids in a predominantly pallidonigral distribution, and we demonstrated changes in solubility and electrophoretic mobility of TDP-43 in brain tissue. The inclusions were highly pleomorphic and predominated in the extrapyramidal system, sparing the cortex, hippocampus and motor neurons. There were no mutations in GRN or TARDBP., Interpretation: Perry syndrome displays unique TDP-43 pathology that is selective for the extrapyramidal system and spares the neocortex and motor neurons.

Atypical furunculosis caused by atypical Aeromonas salmonicida, is an emerging problem in farming of Atlantic cod (Gadus morhua) in Norway, and vaccines are needed. Atypical A. salmonicida comprises a heterogeneous group of bacteria differing in surface antigens such as the A-layer protein and lipopolysaccharides (LPS). Except for one of the experimental oil-adjuvanted whole cell vaccines based on various isolates they all resulted in moderate protection. No clear correlation between vaccine efficacies and the A-protein group or LPS type of the vaccine isolates was revealed, while a correlation between efficacy and the presence of cross-reacting LPS-specific antibodies is indicated.

O-acetylation is one of the major modifications of sialic acids that significantly alters biological properties of the parent molecule. These O-acetylated forms are components of the cellular membrane and can affect physiological and pathological responses. Understanding the role of N-glycans in physiology is of increasing relevance to cellular biologists in various disciplines who study glycoproteomics yet lack information regarding the function of the attached glycans. It is well known that stress may decrease immune function in fish; however, there are only few suitable biomarkers available to monitor the physiological responses under the stress conditions. This study is the first report on the effect of stress on the profile of O-acetylation of sialic acids in fish serum. In order to preserve the relevant structural characteristics as much as possible, native N-glycans were directly analyzed using CE-MS. We have characterized the N-glycans in serum of salmon (Salmo salar) exposed to long-term handling stress (15 s out of the water, daily for 4 wk) and compared with the results obtained from sera of control fish. The results indicated that major N-glycans in salmon serum contained mono-acetylated sialic acids (83%), and that the O-acetylation pattern of sialic acids could be altered by long-term stress.

Ovarian cancer patients experience high levels of anxiety and depression, yet there is little research regarding coping and support of this population. In this study we examined the experiences of women during diagnosis and treatment via 30 semistructured interviews. The interviews were analyzed qualitatively, and five main themes were evident: (1) extreme blunting; (2) having a "forgotten cancer"; (3) traumatic surprise of diagnosis; (4) highs and lows of health care; and (5) support gap experienced postdiagnosis. Currently, there is no readily accessible psychosocial/educational information source for these patients. It is likely that a telephone intervention would be the most effective solution.

A thorough search of the literature has revealed little empirical research on the effects of trauma therapy with incarcerated women with histories of CSA. Psychotherapy, when available in a correctional setting, seems more related to resolving immediate crises that interfere with smooth management of the corrections environment rather than dealing with underlying problems such as CSA. The purpose of this preliminary investigation therefore was to implement and evaluate the efficacy of a time-limited, trauma-focused group intervention with a group of recently-incarcerated women volunteers who had experienced CSA. Five women completed the group plus pre- and post-test measures; a wait-list control group completed measures at the same intervals. Results were mixed in regard to the effectiveness of treatment: decreases were found in the mean Trauma Content (TC/R) scores of the Rorschach Inkblot Method (RIM), but scores on the TSI and the SCL-90-R did not vary greatly. However, women in the control group showed consistent declines in scores during the wait-list period, suggesting the intervention may have helped newly incarcerated women adjust with less symptomatology.

We studied a patient (J.J.) with bilateral damage to those regions of the posterior parietal cortex (PPC) thought to be involved in prism adaptation. We demonstrated, for the first time in a parietal patient, that J.J. was unable to adapt to the visual perturbation induced by the optical prisms with either hand within four times the number of trials required by healthy adult subjects. We offer a novel account for the role of the PPC in prism adaptation: that the reach direction to the veridical target location specified in extrinsic limb-based coordinates must be de-coupled from the gaze direction to the perceived target location specified by intrinsic oculocentric coordinates in order to produce spatially accurate movements. This spatial discrepancy between gaze direction and reach direction may provide the necessary training signal required by the cerebellum to update the current internal model used to maintain spatial congruency between visual and proprioceptive maps of peripersonal space. The hypothesis is discussed in relation to recent disconnectionist accounts of optic ataxia.

To explore how to better educate rural Africans about preventive HIV/AIDS vaccine trials, 15 semi-structured, open-ended interviews were conducted with villagers in Lyantonde, Rakai District, Uganda. This study reports on the findings by focusing on the attitudes, knowledge and questions the rural villagers had about HIV/AIDS-preventive vaccine testing. While several interviewees confused preventive vaccines with therapeutic vaccines, most were clear about the distinction and about key questions to ask about vaccine testing. In addition, some subjects manifested high levels of trust in the likely effectiveness of preventive vaccines, even in the testing stages, most subjects demonstrated the potential to be intelligently inquisitive about the likely effects. In sum, these villagers show the potential to be reliable subjects, motivated for appropriate reasons, and willing to play a role in advancing the progress of HIV/AIDS vaccine development in Africa.

Background: Communication between physicians and patients is an important component of medical encounters and has been identified by the Institute of Medicine as a point of intervention to increase quality of care. In pediatric health maintenance visits, substantial recommended communication, in the form of anticipatory guidance, is not provided., Objective: To examine the effectiveness of an intervention of continuing medical education and process improvement methods to implement "office systems" to improve the delivery of anticipatory guidance for parents of young children., Methods: We performed a randomized controlled trial of a practice-based quality improvement intervention among 44 pediatric practices in North Carolina. In the 22 intervention practices, project staff coached practice staff in auditing performance and identifying, testing, and implementing new care processes to improve delivery of anticipatory guidance. We surveyed parents of 1-month-olds and 6-month-olds regarding their recollection of anticipatory guidance as well as parent knowledge and parent behaviors and used cluster analysis to determine the effects of the intervention., Results: The proportion of parents of 1-month-olds who reported that they received all age-appropriate anticipatory guidance changed from 15.9% (95% confidence interval [CI], 8.9%-26.7%) to 10.0% (95% CI, 5.1%-18.8%) in the control practices and from 7.3% (4.1%-12.9%) to 24.0% (95% CI, 14.6%-36.9%) in the intervention practices (difference between 2 differences, P = .002). The proportion of parents of 6-month-olds who reported that they received all age-appropriate anticipatory guidance changed from 8.2% (95% CI, 3.6%-17.8%) to 5.4% (95% CI, 2.8%-10.2%) in the control practices and from 2.2% (95% CI, 0.8%-5.9%) to 18.1% (95% CI, 10.3%-29.9%) in the intervention practices (difference between 2 differences, P = .001). There were no differences in self-reported parent knowledge and parent behavior., Conclusion: An office system intervention improved parent reports of quantity of anticipatory guidance but did not change parent knowledge or parent behavior. Future research should examine how to use systems improvement methods to improve the impact of anticipatory guidance.

Infectious salmon anemia virus (ISAV) is a very important fish virus in the Northern hemisphere and there is continued interest in understanding the mechanisms of its pathogenesis and persistence in fish. In this study, the permissive fish cell lines SHK-1, CHSE-214 and TO were used to determine whether ISAV-induced cytopathic effect (CPE) is due to apoptosis or necrosis. Characteristic apoptotic DNA fragmentation was observed only in ISAV-infected SHK-1 and CHSE-214 cells. Apoptosis in ISAV-infected SHK-1 cells was confirmed by fragment end-labelling assay, suggesting that CPE in these cells is associated with apoptosis. ISAV-infected TO cells did not undergo apoptosis, but showed leakage of high-mobility group 1 (HMGB1) protein from the nucleus, which is characteristic of cells undergoing necrosis; this suggests that CPE in these cells is associated with necrosis. ISAV-infected SHK-1 cells did not show leakage of HMGB1 protein. Infection with two different strains of ISAV showed that induction of apoptosis was correlated with the appearance of CPE in SHK-1 cells. ISAV-induced apoptosis was inhibited by a pan-caspase inhibitor, Z-VAD-fmk, indicating a caspase-activation pathway. The ISAV putative PB2 protein and proteins encoded by RNA segment 7 bound caspase-8 specifically in vitro, suggesting that these viral proteins may have a role in ISAV-induced apoptosis. These findings demonstrate for the first time that the mechanism of cell death during ISAV infection is dependent on the cell type, which may have implications for ISAV pathogenesis and persistence.

BACKGROUND: Vaccines have virtually eliminated many diseases, but public concerns about their safety could undermine future public health initiatives. OBJECTIVE: To determine Canadians' attitudes and knowledge about vaccines, particularly in view of increasing public concern about bioterrorism and the possible need for emergency immunizations after weaponized anthrax incidents and the events of September 11, 2001. METHOD: A 20-question survey based on well-researched dimensions of vaccine responsiveness was telephone-administered to a random sample of N = 1330 adult Canadians in January, 2002. RESULTS: 1057 (79.5%) completed the survey. Respondents perceived vaccines to be highly effective and demonstrated considerable support for further vaccine research. However, results also indicate a lack of knowledge about vaccines and uncertainty regarding the safety. CONCLUSIONS: Support for vaccines is broad but shallow. While Canadians hold generally positive attitudes about vaccines, support could be undermined by widely publicized adverse events. Better public education is required to maintain support for future public health initiatives.

Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.

Background: Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease., Methods: In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrollment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol., Findings: 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76.8% (95% CI -9.4% to 95.1%) and the intention-to-treat total primary efficacy was 82.6% (21.4% to 96.1%)., Interpretation: PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.

Objective: The most frequent known genetic causes of severe oligospermia (< 5 million sperm/ml) or azoospermia in men are Klinefelter's syndrome (KS), and deletions in the Y chromosome long arm (Yq). We aimed to compare the function of the pituitary-testicular axis in patients with severe oligospermia or azoospermia, idiopathic or associated with Y chromosome deletions or Klinefelter's syndrome (KS) and in control subjects., Patients: We studied 47 men with idiopathic oligo-azoospermia, 42 with Yq deletions (27 AZFc, 13 AZFb and two AZFa) and oligo-azoospermia, 14 with KS and 39 control subjects (total 143)., Measurements: We analysed levels of FSH, inhibin-B, LH, free testosterone and oestradiol in all subjects, and we calculated indexes based on those hormones., Results: Inhibin-B levels were indistinguishable between patients with idiopathic and Y deletion-associated oligo-azoospermia, lowest in the Klinefelter's patients and highest in controls. FSH levels followed the reverse pattern: indistinguishable between patients with idiopathic and deletion-associated oligo-azoospermia, highest in Klinefelter's patients and lowest in controls. Oestradiol, free testosterone and the derived indeces were not different in subjects with Yq deletions compared to those with idiopathic oligo-azoospermia. Among the Yq-deleted patients, no measured or derived parameter differed between the subjects with AZFc deletion and those with AZFb deletion. When non-KS oligo-azoospermic patients were classified according to histology [Sertoli cell-only (SCO), n = 18 or non-Sertoli cell only (non-SCO), n= 18] and compared to KS patients, the hormonal pattern did not differ between SCO and non-SCO subjects, but levels in KS patients were significantly different for FSH, inhibin-B and the FSH/inhibin-B ratio. KS patients not only had lower inhibin-B than SCO and non-SCO oligo-azoospermic men, but also higher FSH levels for any given inhibin-B concentration., Conclusion: Our data show that Y-deleted patients do not have a lesser impairment of Sertoli cell function than patients with idiopathic oligo-azoospermia, and support the concept that the main determinant of inhibin-B production is the germ cell mass. Also, our results suggest that one or more other factors, apart from inhibin-B, may contribute to increased pituitary secretion of FSH in KS patients.

This article describes the collaborative efforts of seven North Carolina counties involved in a home visitation program for new mothers. It explores factors that facilitated and impeded collaboration. Program staff reported strong leadership, shared vision, a heterogeneous mix of partners, establishment of trust, a positive attitude, role delineation, and open communication to be factors contributing to successful collaboration. Lack of guidance about how to collaborate, competition between programs and categorical funding, restrictive confidentiality policies that limit cross-agency access to information, and lack of time and energy were major barriers to achieving integrated service delivery systems.