Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 04/14/16

Πέμπτη 14 Απριλίου 2016

The Relationship of Caffeine Intake with Depression, Anxiety, Stress, and Sleep in Korean Adolescents.

The Relationship of Caffeine Intake with Depression, Anxiety, Stress, and Sleep in Korean Adolescents.

Korean J Fam Med. 2016 Mar;37(2):111-6

Authors: Jin MJ, Yoon CH, Ko HJ, Kim HM, Kim AS, Moon HN, Jung SP

Abstract
BACKGROUND: In various studies in adults, caffeine may increase wakefulness and relieve pain, but caffeine overdose can cause many adverse serious effects on health. Caffeine intake has recently been increasing in adolescents. In spite of importance of caffeine effects on Korean adolescents, there are lack of scientific and systematic studies. The purpose of our study was to identify the relationship between caffeine consumption and effects on adolescents.
METHODS: We performed study on 234 middle school students at one middle school in Daegu using a self-report questionnaire. We divided students to quartiles according to amount of caffeine intake. We used Beck Depression Inventory (BDI) to evaluate the degree of depression and Beck Anxiety Inventory (BAI) to evaluate the degree of anxiety. We also used Insomnia Severity Scale (ISI) to evaluate the degree of insomnia and Global Assessment of Recent Stress (GARS) to evaluate the stress in students. We used logistic regression analysis to identify the relationship between caffeine consumption and effects.
RESULTS: Higher caffeine intake was associated with higher weight, height, lower academic achievement, and higher score in BDI, BAI, ISI, and GARS (P for trend <0.005). Higher caffeine intake quartile was associated with greater odds of having significant depression (BDI ≥10, P for trend=0.011), and insomnia (ISI ≥8, P for trend=0.015) after adjustment for factors that can affect the psychological status.
CONCLUSION: We found that caffeine intake is associated weight, height, academic achievement, and higher score in BDI, BAI, ISI, and GARS. Caffeine intake was positively associated with the severity of depression and the severity of insomnia among adolescents in Korean.

PMID: 27073610 [PubMed]

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Relationship between Changes in Fatigue and Exercise by Follow-Up Period.

Relationship between Changes in Fatigue and Exercise by Follow-Up Period.

Korean J Fam Med. 2016 Mar;37(2):78-84

Authors: Oh SM, Bae WK, Choo SR, Kim HT, Kim HH, Lee SH, Jeong HS

Abstract
BACKGROUND: Fatigue is one of the most common presenting symptoms in primary care in Korea. In this study, we aimed to determine the effect of exercise intervention on the severity of fatigue of unknown medical cause during a period of follow-up.
METHODS: We used the data collected from an outpatient fatigue clinic in Seoul National University Bundang Hospital. The study was conducted from March 3, 2010 to May 31, 2014. We measured the body mass index of each patient and evaluated variables including lifestyle factors (smoking, alcohol consumption, and regular exercise), quality of sleep, anxiety, depression, stress severity, and fatigue severity using questionnaires. A total of 152 participants who completed questionnaires to determine changes in fatigue severity and the effect of exercise for each period were evaluated. We used univariate analysis to verify possible factors related to fatigue and then conducted multivariate analysis using these factors and the literature.
RESULTS: Of 130 patients with the complaint of chronic fatigue for over 6 months, over 90 percent reported moderate or severe fatigue on the Fatigue Severity Scale and Brief Fatigue Inventory questionnaires. The fatigue severity scores decreased and fatigue improved over time. The amount of exercise was increased in the first month, but decreased afterwards.
CONCLUSION: There was no significant relationship between changes in the amount of exercise and fatigue severity in each follow-up period. Randomized controlled trials and a cohort study with a more detailed exercise protocol in an outpatient setting are needed in the future.

PMID: 27073605 [PubMed]

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Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury.

Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury.

Neural Regen Res. 2016 Feb;11(2):248-56

Authors: Qu W, Liu NK, Xie XM, Li R, Xu XM

Abstract
Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.

PMID: 27073377 [PubMed]

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Objectively measured physical activity and plasma metabolomics in the Shanghai Physical Activity Study.

Objectively measured physical activity and plasma metabolomics in the Shanghai Physical Activity Study.

Int J Epidemiol. 2016 Apr 12;

Authors: Xiao Q, Moore SC, Keadle SK, Xiang YB, Zheng W, Peters TM, Leitzmann MF, Ji BT, Sampson JN, Shu XO, Matthews CE

Abstract
BACKGROUND: Physical activity is associated with a variety of health benefits, but the biological mechanisms that explain these associations remain unclear. Metabolomics is a powerful tool to comprehensively evaluate global metabolic signature associated with physical activity and helps to pinpoint the pathways that mediate the health effects of physical activity. There has been limited research on metabolomics and habitual physical activity, and no metabolomics study has examined sedentary behaviour and physical activity of different intensities.
METHODS: In a group of Chinese adults (N= 277), we used an untargeted approach to examine 328 plasma metabolites in relation to accelerometer-measured physical activity, including overall volume of physical activity (physical activity energy expenditure (PAEE) and duration of physically active time) and sedentary time, and measures related to different intensities of physical activity (moderate-to-vigorous activity (MVPA), light activity, average physical activity intensity).
RESULTS: We identified 11 metabolites that were associated with total activity, with a false discovery rate of 0.2 or lower. Notably, we observed generally lower levels of amino acids in the valine, leucine and isoleucine metabolism pathway and of carbohydrates in sugar metabolism among participants with higher activity levels. Moreover, we found that PAEE, time spent in light activity and duration of physically active time were associated with a similar metabolic pattern, whereas the metabolic signature associated with sedentary time mirrored this pattern. In contrast, average activity intensity and time spent in MVPA appeared to be associated with somewhat different metabolic patterns.
CONCLUSIONS: Overall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity.

PMID: 27073263 [PubMed - as supplied by publisher]

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Obstructive Sleep Apnea in Acute Stroke: A Role for Systemic Inflammation.

Obstructive Sleep Apnea in Acute Stroke: A Role for Systemic Inflammation.

Stroke. 2016 Apr 12;

Authors: Ifergane G, Ovanyan A, Toledano R, Goldbart A, Abu-Salame I, Tal A, Stavsky M, Novack V

Abstract
BACKGROUND AND PURPOSE: Sleep-disordered breathing is common among patients with stroke resulting in 4- to 6-fold higher prevalence of obstructive sleep apnea (OSA). We prospectively evaluated clinical characteristics and laboratory markers of inflammation and coagulability associated with OSA severity during the acute post stroke period.
METHODS: Consecutive patients admitted to the department of Neurology after an acute ischemic stroke were evaluated during the first 48 hours of symptom onset using Watch peripheral arterial tonometry, a wrist-worn ambulatory sleep study device that utilizes peripheral arterial tonometry. Morning blood samples of the patient were tested for tumor necrosis factor, interleukin-6, and plasminogen activator inhibitor-1 levels.
RESULTS: A total of 43 patients with acute stroke were admitted during the study period, 22 (51%) of which have been found to have moderate sleep apnea (apnea hypopnea index [AHI]≥15), AHI≥5 was found in 86% of the patients, and severe OSA (AHI≥30) in 32.5%. Patients with OSA (AHI≥15) did not differ from the rest in stroke severity or symptoms, yet they had higher prevalence of recurrent stroke and atrial fibrillation. All 3 biomarkers levels were higher among patients with AHI≥15: tumor necrosis factor (6.39 versus 3.57 pg/mL), interleukin-6 (6.64 versus 3.14 pg/mL), and plasminogen activator inhibitor-1 (176.64 versus 98.48 pg/mL). After the stratification of AHI into 3 groups (AHI<5, 5-14, and ≥15), the analysis showed that only the highest AHI group differed from the other 2 groups in biomarkers levels.
CONCLUSIONS: Use of bed-side somnography technology revealed that in an unselected sample of patients with acute ischemic stroke, almost 90% had sleep-disordered breathing with third having severe form of the disorder. Sleep-disordered breathing was associated with significantly increased levels of inflammatory biomarkers, providing possible pathophysiological explanation of OSA-associated stroke risk. These results warrant prospective screening of patients with stroke for the presence of sleep-disordered breathing and lay the rationale for an interventional trial.

PMID: 27073238 [PubMed - as supplied by publisher]

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Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening.

Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening.

Int J Stroke. 2016 Apr 12;

Authors: Swartz RH, Bayley M, Lanctôt KL, Murray BJ, Cayley ML, Lien K, Sicard MN, Thorpe KE, Dowlatshahi D, Mandzia JL, Casaubon LK, Saposnik G, Perez Y, Sahlas DJ, Herrmann N

Abstract
Stroke can cause neurological impairment ranging from mild to severe, but the impact of stroke extends beyond the initial brain injury to include a complex interplay of devastating comorbidities including: post-stroke depression, obstructive sleep apnea, and cognitive impairment ("DOC"). We reviewed the frequency, impact, and treatment options for each DOC condition. We then used the Ottawa Model of Research Use to examine gaps in care, understand the barriers to knowledge translation, identification, and addressing these important post-stroke comorbidities. Each of the DOC conditions is common and result in poorer recovery, greater functional impairment, increased stroke recurrence and mortality, even after accounting for traditional vascular risk factors. Despite the strong relationships between DOC comorbidities and these negative outcomes as well as recommendations for screening based on best practice recommendations from several countries, they are frequently not assessed. Barriers related to the nature of the screening tools (e.g., time consuming in high-volume clinics), practice environment (e.g., lack of human resources or space), as well as potential adopters (e.g., equipoise surrounding the benefits of treatment for these conditions) pose challenges to routine screening implementation. Simple, feasible approaches to routine screening coupled with appropriate, evidence-based treatment protocols are required to better identify and manage depression, obstructive sleep apnea, and cognitive impairment symptoms in stroke prevention clinic patients to reduce the impact of these important post-stroke comorbidities. These tools may in turn facilitate large-scale randomized controlled treatment trials of interventions for DOC conditions that may help to improve cardiovascular outcomes after stroke or TIA.

PMID: 27073189 [PubMed - as supplied by publisher]

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Kleine-Levin Syndrome.

Kleine-Levin Syndrome.

Curr Treat Options Neurol. 2016 Jun;18(6):24

Authors: Sum-Ping O, Guilleminault C

Abstract
OPINION STATEMENT: Kleine-Levin Syndrome [KLS] is often under-recognized and also misdiagnosed. When suspicion for KLS is raised, a thorough clinical evaluation should be performed, including detailed history from family members and a neurologic and psychiatric examination. Additional studies may include PSG, EEG, neuroimaging, as well as serological and CSF studies to rule out alternative diagnoses as clinically indicated. After arriving at a diagnosis of KLS, the foundation of care is supportive. Patients and their families should be provided with education about the disease. During symptomatic periods, patients should be allowed to rest at home under caregiver supervision. Caregivers should pay special attention to the patient's eating habits and mood. Patients should not be allowed to drive or operate heavy machinery during these episodes. In between episodes, avoidance of reported triggers, such as alcohol and infection are encouraged as is maintenance of a regular sleep-wake cycle. Pharmacologic therapy has not been well-studied and for most patients is not necessary. For more severe cases, targeted symptomatic therapy, such as modafinil or amantadine for somnolence or risperidone for psychosis may be considered depending on the patient's symptomatology. Lithium has the best data to support its use as a prophylactic agent and for patients with severe or frequent episodes, may be considered.

PMID: 27073070 [PubMed]

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Bodily pain, social support, depression symptoms and stroke history are independently associated with sleep disturbance among the elderly: a cross-sectional analysis of the Fujiwara-kyo study.

Bodily pain, social support, depression symptoms and stroke history are independently associated with sleep disturbance among the elderly: a cross-sectional analysis of the Fujiwara-kyo study.

Environ Health Prev Med. 2016 Apr 12;

Authors: Kishimoto Y, Okamoto N, Saeki K, Tomioka K, Obayashi K, Komatsu M, Kurumatani N

Abstract
OBJECTIVE: To investigate independent effects of various factors associated with sleep disturbance among community-dwelling elderly individuals.
METHODS: We analyzed data obtained from 3732 individuals aged ≥65 years who responded to a self-administered questionnaire and participated in a structured interview which assessed the Pittsburgh Sleep Quality Index (PSQI), subjective bodily pain, the Jichi Medical School Social Support Scale, the Geriatric Depression Scale (GDS-15), health status, and demographic characteristics. Sleep disturbance was defined as a global PSQI score >5.5, which was used as a dependent variable in multiple logistic regression analysis to determine adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) of related factors.
RESULTS: We identified a significant increase in the adjusted ORs for female (OR 1.56, 95 % CI 1.34-1.83), age ≥80 years (1.31, 1.01-1.69), history of stroke (1.44, 1.08-1.92), and a GDS-15 score ≥6 as compared to 0-2 (2.29, 1.86-2.81), with regard to sleep disturbance. Participants with severe or very severe bodily pain had the highest adjusted OR (3.00, 2.15-4.19), and those with very mild bodily pain also had a relatively high OR (1.30, 1.06-1.60), relative to those without subjective bodily pain. In addition, compared with participants with strong social support from spouse or family, those with weak social support had significantly increased adjusted ORs (1.21, 1.01-1.44, 1.44, 1.23-1.70, respectively).
CONCLUSIONS: The present study indicates that sleeping disturbances among the elderly are closely associated with social support from a spouse and family. They are also associated with pain, even at stages in which subjective bodily pain is very mild.

PMID: 27072924 [PubMed - as supplied by publisher]

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Psychosocial interventions for people with young onset dementia and their carers: a systematic review.

Psychosocial interventions for people with young onset dementia and their carers: a systematic review.

Int Psychogeriatr. 2016 Apr 13;:1-14

Authors: Richardson A, Pedley G, Pelone F, Akhtar F, Chang J, Muleya W, Greenwood N

Abstract
BACKGROUND: Dementia in younger people, known as young (YOD) or early onset dementia (EOD), can pose significant challenges. YOD is often diagnosed in those in paid employment who have relatively young children, leading to different challenges to those for older people. It is therefore very important to provide support tailored to their specific needs. This systematic review aimed to synthesize the literature investigating the impact of psychosocial interventions for people with YOD and their family carers.
METHOD: Eight electronic databases were searched and three key journals were also hand searched. Narrative synthesis of the selected articles was undertaken.
RESULTS: Of the 498 records identified, 495 were ineligible after application of the exclusion criteria. The final sample included three studies, all of which were employment-based. Two were qualitative and one used mixed methods. Study quality was mixed. People with YOD and their carers reported benefits from participating in work-based interventions designed for those with YOD, including improved self-esteem and sense of purpose. Social contact was highlighted. Despite cognitive decline, maintenance in well-being was also reported. Carers described benefits for people with YOD, which extended outside the intervention, e.g. enhanced sleep and mood. The impact of the interventions on carers was not assessed.
CONCLUSIONS: This review suggests work-based interventions providing supported, meaningful work outside the home can be beneficial. However, the dearth of studies, the lack of focus on family carers and their mixed quality demonstrate the need for better quality, mixed methods research with larger sample sizes.

PMID: 27072752 [PubMed - as supplied by publisher]

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Recent Updates on Development of Drug Molecules for Human African Trypanosomiasis.

Recent Updates on Development of Drug Molecules for Human African Trypanosomiasis.

Curr Top Med Chem. 2016 Apr 13;

Authors: Grewal AS, Pandita D, Bhardwaj S, Lather V

Abstract
Human African trypanosomiasis (HAT, better called as sleeping sickness), caused by two morphologically identicalprotozoan parasite Trypanosoma bruceiis transmitted by the bite of tsetse fliesof Glossinagenus, mainly in the rural areas of the sub-Saharan Africa.HAT is one of the neglected tropical diseases and is characterized by sleep disturbance as the main symptom, hence is called as sleeping sickness. As it is epidemic in the poorest population of Africa, there is limited availability of safe and cost-effective tools for controlling the disease. Trypanosoma bruceigambiensecauses sleeping sickness in Western and Central Africa,whereasTrypanosoma bruceirhodesienseis the reason for prevalence of sleeping sickness in Eastern and Southern Africa. For the treatment of sleeping sickness, only five drugs have been approved suramin, pentamidine, melarsoprol, eflornithine and nifurtimox. Various small molecules of diverse chemical nature have been synthesizedfortargeting HAT and many of them are in the clinical trialsincluding fexinidazole (phase I completed) and SCYX-7158 (advanced in phase I). The present work has been planned to reviewvarious types of small molecules developed in the last 10 years having potent antitrypanosoma activity likely to be beneficial in sleeping sickness along withdifferent natural anti-HAT agents.

PMID: 27072715 [PubMed - as supplied by publisher]

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Sound Source Localization by Normal-Hearing Listeners, Hearing-Impaired Listeners and Cochlear Implant Listeners

Objective: Our primary aim was to determine whether listeners in the following patient groups achieve localization accuracy within the 95th percentile of accuracy shown by younger or older normal-hearing (NH) listeners: (1) hearing impaired with bilateral hearing aids, (2) bimodal cochlear implant (CI), (3) bilateral CI, (4) hearing preservation CI, (5) single-sided deaf CI and (6) combined bilateral CI and bilateral hearing preservation. Design: The listeners included 57 young NH listeners, 12 older NH listeners, 17 listeners fit with hearing aids, 8 bimodal CI listeners, 32 bilateral CI listeners, 8 hearing preservation CI listeners, 13 single-sided deaf CI listeners and 3 listeners with bilateral CIs and bilateral hearing preservation. Sound source localization was assessed in a sound-deadened room with 13 loudspeakers arrayed in a 180-degree arc. Results: The root mean square (rms) error for the NH listeners was 6 degrees. The 95th percentile was 11 degrees. Nine of 16 listeners with bilateral hearing aids achieved scores within the 95th percentile of normal. Only 1 of 64 CI patients achieved a score within that range. Bimodal CI listeners scored at a level near chance, as did the listeners with a single CI or a single NH ear. Listeners with (1) bilateral CIs, (2) hearing preservation CIs, (3) single-sided deaf CIs and (4) both bilateral CIs and bilateral hearing preservation, all showed rms error scores within a similar range (mean scores between 20 and 30 degrees of error). Conclusion: Modern CIs do not restore a normal level of sound source localization for CI listeners with access to sound information from two ears.
Audiol Neurotol 2016;21:127-131

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The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo

Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Ménière's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up.
Audiol Neurotol 2016;21:132-140

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Viruses, Vol. 8, Pages 100: Purification and Biochemical Characterisation of Rabbit Calicivirus RNA-Dependent RNA Polymerases and Identification of Non-Nucleoside Inhibitors

Rabbit haemorrhagic disease virus (RHDV) is a calicivirus that causes acute infections in both domestic and wild European rabbits (Oryctolagus cuniculus). The virus causes significant economic losses in rabbit farming and reduces wild rabbit populations. The recent emergence of RHDV variants capable of overcoming immunity to other strains emphasises the need to develop universally effective antivirals to enable quick responses during outbreaks until new vaccines become available. The RNA-dependent RNA polymerase (RdRp) is a primary target for the development of such antiviral drugs. In this study, we used cell-free in vitro assays to examine the biochemical characteristics of two rabbit calicivirus RdRps and the effects of several antivirals that were previously identified as human norovirus RdRp inhibitors. The non-nucleoside inhibitor NIC02 was identified as a potential scaffold for further drug development against rabbit caliciviruses. Our experiments revealed an unusually high temperature optimum (between 40 and 45 °C) for RdRps derived from both a pathogenic and a non-pathogenic rabbit calicivirus, possibly demonstrating an adaptation to a host with a physiological body temperature of more than 38 °C. Interestingly, the in vitro polymerase activity of the non-pathogenic calicivirus RdRp was at least two times higher than that of the RdRp of the highly virulent RHDV.

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Issue Information - Table of Contents

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Spleen hypoplasia leads to abnormal stress hematopoiesis in mice with loss of Pbx homeoproteins in splenic mesenchyme

Abstract

The spleen plays critical roles in immunity and also provides a permissive microenvironment for hematopoiesis. Previous studies have reported that the TALE-class homeodomain transcription factor Pbx1 is essential in hematopoietic stem and progenitor cells (HSPCs) for stem cell maintenance and progenitor expansion. However, the role of Pbx1 in the hematopoietic niche has not been investigated. Here we explored the effects that genetic perturbation of the splenic mesenchymal niche has on hematopoiesis upon loss of members of the Pbx family of homeoproteins. Splenic mesenchyme-specific inactivation of Pbx1 (SKO) on a Pbx2- or Pbx3-deficient genetic background (DKO) resulted in abnormal development of the spleen, which is dysmorphic and severely hypoplastic. This phenotype, in turn, affected the number of HSPCs in the fetal and adult spleen at steady state, as well as markedly impairing the kinetics of hematopoietic regeneration in adult mice after sub-lethal and lethal myelosuppressive irradiation. Spleens of mice with compound Pyx deficiency 8 days following sublethal irradiation displayed significant downregulation of multiple cytokine-encoding genes, including KitL/SCF, Cxcl12/SDF-1, IL-3, IL-4, GM-CSF/Csf2 IL-10, and Igf-1, compared with controls. KitL/SCF and Cxcl12/SDF-1 were recently shown to play key roles in the splenic niche in response to various haematopoietic stresses such as myeloablation, blood loss, or pregnancy. Our results demonstrate that, in addition to their intrinsic roles in HSPCs, non-cell autonomous functions of Pbx factors within the splenic niche contribute to the regulation of hematopoiesis, at least in part via the control of KitL/SCF and Cxcl12/SDF-1. Furthermore, our study establishes that abnormal spleen development and hypoplasia have deleterious effects on the efficiency of hematopoietic recovery after bone marrow injury.

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Does subchondral bone of the equine proximal phalanx adapt to race training?

Abstract

Sagittal fractures of the first phalanx are a common, potentially catastrophic injury in racehorses. These fractures are often linked to an acute, one time, biomechanical event; however, recent evidence implies that chronic exposure to stress can lead to the accumulation of bony changes that affect the structural integrity of the bone and increase the likelihood of fracture. The aim of the study was to compare variations of two common metrics of bone adaptation – subchondral bone density and thickness across the proximal articular surface of the first phalanx in Thoroughbred horses that (1) raced but never experienced a first phalanx fracture (Raced Control); (2) raced and had experienced fracture of the contralateral first phalanx (Contralateral to Fracture); (3) had never raced or experienced a first phalanx fracture (Unraced Control). A total of 22 first phalangeal bones were sampled post-mortem and imaged using micro-computed tomography calibrated for mineral density measures. Measurements of volumetric subchondral bone mineral density and thickness were taken from images at five sites from medial to lateral, in three coronal planes (25, 50 and 75% dorsal-palmar). At each of the 15 sites, measurements were repeated and averaged across 10 adjacent micro-computed tomography slices of bone, spanning 0.75 mm. The magnitude and variance of these measurements were compared between sites and between cohorts with non-parametric statistical tests. Across the proximal osteochondral surface of the first phalanx, the pattern of subchondral bone volumetric bone mineral density and thickness varied with each coronal section studied. The subchondral bone thickness was greater for the central and dorsal coronal sections, compared with the palmar section. For the race-fit groups (Raced Control and Contralateral to Fracture), the highest volumetric bone mineral density was in the central sagittal groove. The volumetric bone mineral density was significantly greater in the sagittal groove in the central coronal section in the raced than the unraced group. The Contralateral to Fracture group demonstrated significantly greater variance of volumetric bone mineral density compared with the Raced Control and Unraced Control (P < 0.0001), with no difference in variance noted between the Raced Control and Unraced Control groups. There was a small (R rank = 0.3) but significant correlation between subchondral bone volumetric bone mineral density and thickness in the Contralateral to Fracture group (P = 0.005). The findings demonstrate that differences exist in subchondral bone volumetric bone mineral density and thickness across the proximal osteochondral surface of the equine first phalanx in horses with different training histories. The findings also demonstrate that the subchondral bone of the sagittal groove of the equine first phalanx adapts to race-training in the race-fit groups (Raced Control and Contralateral to Fracture) with an increase in volumetric bone mineral density relative to unraced controls. Within the race-trained groups, the Contralateral to Fracture bones had a greater variance of volumetric bone mineral density, suggesting that stress-induced bone adaptation had become more erratic, potentially contributing to the aetiology of sagittal fractures of the first phalanx in the Thoroughbred racehorse.

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MEK inhibitor treatment is effective in a patient with metastatic carcinoma of the ampulla of Vater with BRAF and NRAS mutations shown by next-generation sequencing.

Here, we present a case of an 84-year-old woman who developed obstructive jaundice and was diagnosed with nonoperable adenocarcinoma originating from the ampulla of Vater, a lethal disease with a median overall survival of less than a year. Her tumor was examined by next-generation sequencing, which showed BRAF and NRAS mutations. To target these mutations, a MEK inhibitor was chosen for treatment. The patient has been treated with a MEK inhibitor for the last 12 months since diagnosis, with clinical and laboratory improvement and manageable side effects. PET-computed tomography imaging has shown stable disease or improvement in the primary and metastatic lesions. This is the first case report of an ampulla of a Vater cancer patient with NRAS and BRAF mutations, identified in next-generation sequencing, and treated successfully with a MEK inhibitor. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Antioxidants in antidiabetic drugs may fuel cancer spread, mouse study shows: https://t.co/n74Q9CtThR

Antioxidants in antidiabetic drugs may fuel cancer spread, mouse study shows: https://t.co/n74Q9CtThR

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Mathematical model of immune evasion by tumour cells could help focus treatments https://t.co/cn69rDdfUW

Mathematical model of immune evasion by tumour cells could help focus treatments https://t.co/cn69rDdfUW

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Join the experts live today to discuss new agents in multiple myeloma - sign up now #HMELive https://t.co/uykLmUdizP https://t.co/ZiKiI6B3il

Join the experts live today to discuss new agents in multiple myeloma - sign up now #HMELive https://t.co/uykLmUdizP https://t.co/ZiKiI6B3il

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Hydromagnetic Stability of Metallic Nanofluids (Cu-Water and Ag-Water) Using Darcy-Brinkman Model

Thermal convection of a nanofluid layer in the presence of imposed vertical magnetic field saturated by a porous medium is investigated for both-free, rigid-free, and both-rigid boundaries using Darcy-Brinkman model. The effects of Brownian motion and thermophoretic forces due to the presence of nanoparticles and Lorentz’s force term due to the presence of magnetic field have been considered in the momentum equations along with Maxwell’s equations. Keeping in mind applications of flow through porous medium in geophysics, especially in the study of Earth’s core, and the presence of nanoparticles therein, the hydromagnetic stability of a nanofluid layer in porous medium is considered in the present formulation. An analytical investigation is made by applying normal mode technique and Galerkin type weighted residuals method and the stability of Cu-water and Ag-water nanofluids is compared. Mode of heat transfer is through stationary convection without the occurrence of oscillatory motions. Stability of the system gets improved appreciably by raising the Chandrasekhar number as well as Darcy number whereas increase in porosity hastens the onset of instability. Further, stability of the system gets enhanced as we proceed from both-free boundaries to rigid-free and to both-rigid boundaries.

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Suppression of Parathyroid Hormone in a Patient with Severe Magnesium Depletion

Hypomagnesemia is often associated with coexisting electrolyte abnormalities like hypokalemia and hypocalcemia. Hypocalcemia has been shown to be secondary to hypoparathyroidism induced by hypomagnesemia. Here, we discuss a case of a patient with severe hypomagnesemia and associated hypocalcemia. A 38-year-old lady was admitted to the hospital for weakness of lower extremities and an eventual fall. The exam was significant for decreased motor strength and some paresthesias. The laboratory data was significant for hypomagnesemia, hypokalemia, and low parathyroid level in the face of hypocalcemia. After replacing magnesium, the parathyroid hormone levels normalized and led to eventual correction of calcium levels without any additional calcium replacement therapy. There was complete symptom resolution with correction of electrolyte abnormalities. This case highlights the importance of looking for all associated abnormalities in a patient with hypomagnesemia and starting the replacement therapy by first replacing the magnesium and then the others as needed. Replacing the magnesium alone may correct the hypoparathyroidism and eliminate the need for calcium replacement.

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Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats

The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200–230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin () were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes.

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Prevalence of Diabetic Foot Disease in Patients with Diabetes Mellitus under Renal Replacement Therapy in Lleida, Spain

Aim. To assess the prevalence of diabetic foot and other associated conditions in patients with diabetes mellitus under renal replacement in the region of Lleida, Spain. Methods. This was an observational, cross-sectional study of 92 dialysis-treated diabetic patients. Besides a podiatric examination, we explored the presence of cardiovascular risk factors, late diabetes complications, including peripheral neuropathy, atherosclerotic disease, and peripheral artery disease. We assessed risk factors for foot ulceration and amputation by logistic regression. Results. Prevalent diabetic foot was found in 17.4% of patients, foot deformities were found in 54.3%, previous ulcer was found in 19.6%, and amputations were found in 16.3%; and 87% of them had some risk of suffering diabetic foot in the future. We observed a high prevalence of patients with peripheral neuropathy and peripheral artery disease (89.1% and 64.2%, resp.). Multivariable analysis identified diabetic retinopathy and advanced atherosclerotic disease (stenosing carotid plaques) as independent risk factors for foot ulceration ( and , resp.) and diabetic retinopathy also as an independent risk factor for lower-limb amputations (). Moreover, there was a temporal association between the initiation of dialysis and the incidence of amputations. Conclusion. Diabetic patients receiving dialysis therapy are at high risk of foot complications and should receive appropriate and intensive foot care.

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Algorithms for Pallet Building and Truck Loading in an Interdepot Transportation Problem

This paper deals with the problem of a logistics company that has to serve its customers by first putting the products on pallets and then loading the pallets into trucks. Besides the standard geometric constraints of products not overlapping each other and not exceeding the dimensions of pallets and trucks, in this real problem, there are many other constraints, related to the total weight of the load, the maximum weight supported by each axle, and the distribution of the load inside the truck. Although the problem can be decomposed into two phases, pallet loading and truck loading, we have taken a combined approach, building and placing pallets at the same time. For each position in the truck, a pallet is built and tailored for that position according to the constraints of height and weight. We have developed a GRASP algorithm, in which the constructive algorithm is randomized and an improvement phase is added to obtain high-quality solutions. The algorithm has been tested on two sets of real instances with different characteristics, involving up to 44 trucks. The results show that solutions with an optimal or near optimal number of trucks are obtained in very short computing times.

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Evaluation of Bus Vibration Comfort Based on Passenger Crowdsourcing Mode

Vibration comfort is an important factor affecting the quality of service (QoS) of bus. In order to make people involved in supervising bus’s vibration comfort and improve passengers’ riding experience, a novel mode of passenger crowdsourcing is introduced. In this paper, comfort degree of bus vibration is calculated from bus’s vibration signals collected by passengers’ smartphones and sent through WiFi to the Boa web server which shows the vibration comfort on the LCD deployed in bus and maybe trigger alarm lamp when the vibration is beyond the threshold. Three challenges here have been overcome: firstly, space coordinate transformation algorithm is used to solve the constant drift of signals collected; secondly, a low-pass filter is designed to isolate gravity from signals real-timely via limited computing resources; thirdly, an embedded evaluation system is developed according to the calculation procedure specified by criterion ISO 2631-1997. Meanwhile, the model proposed is tested in a practical running environment, the vibration data in whole travel are recorded and analyzed offline. The results show that comfort degree of vibration obtained from the experimental system is identical with the truth, and this mode is proved to be effective.

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Receptivity of Boundary Layer over a Blunt Wedge due to Freestream Pulse Disturbances at Mach 6

Direct numerical simulation (DNS) of a hypersonic compressible flow over a blunt wedge with fast acoustic disturbances in freestream is performed. The receptivity characteristics of boundary layer to freestream pulse acoustic disturbances are numerically investigated at Mach 6, and the frequency effects of freestream pulse wave on boundary layer receptivity are discussed. Results show that there are several main disturbance mode clusters in boundary layer under acoustic pulse wave, and the number of main disturbance clusters decreases along the streamwise. As disturbance wave propagates from upstream to downstream direction, the component of the modes below fundamental frequency decreases, and the component of the modes above second harmonic components increases quickly in general. There are competition and disturbance energy transfer between different boundary layer modes. The nose boundary layer is dominated by the nearby mode of fundamental frequency. The number of the main disturbance mode clusters decreases as the freestream disturbance frequency increases. The frequency range with larger growth narrows along the streamwise. In general, the amplitudes of both fundamental mode and harmonics become larger with the decreasing of freestream disturbance frequency. High frequency freestream disturbance accelerates the decay of disturbance wave in downstream boundary layer.

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Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features’ relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality.

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The Influence of Psychiatric Comorbidity on Inpatient Outcomes following Distal Humerus Fractures

Background. The influence of psychiatric comorbidity on outcomes following inpatient management of upper extremity fractures is poorly understood. Methods. The National Hospital Discharge Survey was queried to identify patients admitted to US hospitals with distal humerus fractures between 1990 and 2007. Patients were subdivided into 5 groups: depression, anxiety, schizophrenia, dementia, and no psychiatric comorbidity. Multivariable logistic regression analysis identified independent risk factors for adverse events, requirement of blood transfusion, and discharge to another inpatient facility. Results. A cohort representative of 526,185 patients was identified as having a distal humerus fracture. Depression, anxiety, and dementia were independently associated with higher odds of in-hospital adverse events (). Depression was associated with higher odds of inpatient blood transfusion (). Depression, schizophrenia, and dementia were associated with higher odds of nonroutine discharge to another inpatient facility (). Patients with a diagnosis of schizophrenia had a mean of 12 () more days of care than patients with no psychiatric comorbidity. Discussion. Patients with comorbid psychiatric illness who are admitted to hospitals with distal humerus fractures are at increased risk of inpatient adverse events and posthospitalization care.

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Clostridium difficile Enterocolitis and Reactive Arthritis: A Case Report and Review of the Literature

Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered.

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Acute Corneal Toxicity of Diquas

Aim: This study aimed to investigate acute corneal toxicity of commercially available diquafosol 3% ophthalmic solution (Diquas®), which contains C12 benzalkonium chloride (BAC) as a preservative. Methods: Corneal transepithelial electrical resistance (TER) changes after a 60-second exposure to Diquas® (diquafosol 3% preserved with 0.0075% C12 BAC); 0.0075% C12 BAC and 0.0075% C12, C14, C16 BAC mixture were measured in living rabbits. Corneal damage was also examined by scanning electron microscopy (SEM). Hank's balanced salt solution (HBSS) was used as a control. Results: Diquas® and 0.0075% C12 BAC did not produce any significant decrease in the corneal TER as compared to the HBSS control eyes. There was a significant decrease in the corneal TER after exposure of the cornea to the 0.0075% C12, C14, C16 BAC mixture (p Conclusion: The acute corneal toxicity of Diquas® is less than that of the 0.0075% BAC mixture. Diquas® preserved with 0.0075% C12 BAC did not show acute corneal toxicity.
Pharmacology 2016;98:56-61

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Prevalence and Risk Factors for Post-Traumatic Stress Reaction Among Resident Survivors of the Tsunami That Followed the Great East Japan Earthquake, March 11, 2011

Research Articles
Chieko Matsubara, Hitoshi Murakami, Koubun Imai, Tetsuya Mizoue, Hidechika Akashi, Chiaki Miyoshi, Tamotsu Nakasa
Disaster Medicine and Public Health Preparedness,FirstView Article(s), 8 pages

Abstract

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Sharon Whelan (1948-2016)

The International Agency for Research on Cancer (IARC) is deeply saddened by the passing of Sharon Whelan, an early staff of the Agency, who died on Tuesday 5 April 2016. Our deepest sympathy is with her son, Ben.

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Author response: 'Does cadmium exposure contribute to depressive symptoms in the elderly population?

We thank Dr Tomoyuki Kawada1 for his interest in our manuscript entitled ‘Does cadmium exposure contribute to depressive symptoms in the elderly population?’2 In the letter, Dr Kawada depicted three possible reasons for the inconsistent results of our study: limited statistical power, use of blood cadmium as marker of cadmium exposure and the presence of other potential confounding variables.

First, we agree with Dr Kawada's opinion on the limited statistical power of the study regarding the small number of depression patients in the second and the third visit data. In our study, the point estimates for the association between blood cadmium levels and elderly depressive symptoms were not consistent across the three visits. The direction of the point estimate at the second and the third visit should be consistent as long as depression patients are similarly distributed across the quartile group as their distribution at...

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Blood cadmium level in the elderly population: perspective for the cause of inconsistent results

Han et al1 investigated the association between blood cadmium levels (B-Cd) and depression in 395 people, aged 60 years or older. Survey was conducted three times, and positive association between B-Cd and depression was only observed in the first visit. The authors used the Korean version of the Short Form Generic Depression Scale test (SGDS-K) for screening depression and logistic regression model was used for the analysis. I present my speculation on their statistical inconsistency.

First, the authors well recognised the relatively small number of participants and depression cases, especially in the second and the third visit data. Even in the first visit data, the number of depression cases was only 50. In their tables 3–5, wide ranges of 95% CIs were observed. There is a limitation in the total number of events for logistic regression analysis.2 Peduzzi et al3 simulated the effect of...

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Interventions to increase the reporting of occupational diseases by physicians: a Cochrane systematic review

Introduction

Under-reporting of occupational diseases is an important issue in many countries. Timely and complete reporting is fundamental to a successful physician-based public health surveillance system and to plan intervention programmes and allocation of resources.

For physicians, the main reasons for under-reporting consist of lack of awareness regarding reporting requirements, time and effort involved in reporting and lack of benefit from reporting.

There are no systematic reviews of the effects of interventions for increasing the reporting (or reducing the under-reporting) of occupational diseases. Therefore, we conducted a Cochrane systematic review to evaluate the effectiveness of interventions aimed at increasing the reporting of occupational diseases by physicians.1

Methods

We searched the Cochrane Occupational Safety and Health Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, OSH UPDATE, Database of Abstracts of Reviews of Effects (DARE), Open-SIGLE and Health Evidence, up...

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Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK

Objectives

There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents.

Methods

For each day for 2011–2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season.

Results

For single day exposure, we found consistent associations between adult (15–64 years) cardiovascular and paediatric (0–14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust.

Conclusions

Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations.

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Expected number of asbestos-related lung cancers in the Netherlands in the next two decades: a comparison of methods

Objectives

Exposure to asbestos fibres increases the risk of mesothelioma and lung cancer. Although the vast majority of mesothelioma cases are caused by asbestos exposure, the number of asbestos-related lung cancers is less clear. This number cannot be determined directly as lung cancer causes are not clinically distinguishable but may be estimated using varying modelling methods.

Methods

We applied three different modelling methods to the Dutch population supplemented with uncertainty ranges (UR) due to uncertainty in model input values. The first method estimated asbestos-related lung cancer cases directly from observed and predicted mesothelioma cases in an age-period-cohort analysis. The second method used evidence on the fraction of lung cancer cases attributable (population attributable risk (PAR)) to asbestos exposure. The third method incorporated risk estimates and population exposure estimates to perform a life table analysis.

Results

The three methods varied substantially in incorporated evidence. Moreover, the estimated number of asbestos-related lung cancer cases in the Netherlands between 2011 and 2030 depended crucially on the actual method applied, as the mesothelioma method predicts 17 500 expected cases (UR 7000–57 000), the PAR method predicts 12 150 cases (UR 6700–19 000), and the life table analysis predicts 6800 cases (UR 6800–33 850).

Conclusions

The three different methods described resulted in absolute estimates varying by a factor of ~2.5. These results show that accurate estimation of the impact of asbestos exposure on the lung cancer burden remains a challenge.

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A cost-benefit analysis of peer coaching for overhead lift use in the long-term care sector in Canada

Objectives

To evaluate whether a peer-coaching programme for patient lift use in British Columbia, Canada, was effective and cost-beneficial.

Methods

We used monthly panel data from 15 long-term care facilities from 2004 to 2011 to estimate the number of patient-handling injuries averted by the peer-coaching programme using a generalised estimating equation model. Facilities that had not yet introduced the programme served as concurrent controls. Accepted lost-time claim counts related to patient handling were the outcome of interest with a denominator of full-time equivalents of nursing staff. A cost-benefit approach was used to estimate the net monetary gains at the system level.

Results

The coaching programme was found to be associated with a reduction in the injury rate of 34% during the programme and 56% after the programme concluded with an estimated 62 lost-time injury claims averted. 2 other factors were associated with changes in injury rates: larger facilities had a lower injury rate, and the more care hours per bed the lower the injury rate. We calculated monetary benefits to the system of $748 431 and costs of $894 000 (both in 2006 Canadian dollars) with a benefit-to-cost ratio of 0.84. The benefit-to-cost ratio was –0.05 in the worst case scenario and 2.31 in the best case scenario. The largest cost item was peer coaches’ time. A simulation of the programme continuing for 5 years with the same coaching intensity would result in a benefit-to-cost ratio of 0.63.

Conclusions

A peer-coaching programme to increase effective use of overhead lifts prevented additional patient-handling injuries but added modest incremental cost to the system.

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Self-guided internet-based and mobile-based stress management for employees: results of a randomised controlled trial

Objective

This randomised controlled trial (RCT) aimed to evaluate the efficacy of a self-guided internet-based stress management intervention (iSMI) for employees compared to a 6-month wait-list control group (WLC) with full access for both groups to treatment as usual.

Method

A sample of 264 employees with elevated symptoms of perceived stress (Perceived Stress Scale, PSS-10 ≥22) was randomly assigned to either the iSMI or to the WLC. The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques. Self-report data were assessed at baseline, at 7 weeks and at 6 months following randomisation. The primary outcome was perceived stress (PSS-10). The secondary outcomes included other relevant mental-related and work-related health outcomes. Data were analysed based on intention-to-treat principles.

Results

The iSMI participants showed a significantly higher reduction in perceived stress from baseline to post-treatment at 7 weeks (d=0.96, 95% CI 0.70 to 1.21) and to the 6-month follow-up (d=0.65, 95% CI 0.40 to 0.89) compared to the WLC. Significant differences with small to moderate effect sizes were also found for depression, anxiety, emotional exhaustion, sleeping problems, worrying, mental health-related quality of life, psychological detachment, emotion regulation skills and presenteeism, in favour of the experimental group. At the 6 -month follow-up, all outcomes remained significantly better for the experimental group with the exception of work engagement, physical health-related quality of life and absenteeism, which were not found to significantly differ between the iSMI and WLC groups.

Conclusions

The iSMI investigated in this study was found to be effective in reducing typical mental-related and work-related health symptoms of stressed employees. Internet-based self-guided interventions could be an acceptable, effective and potentially cost-effective approach to reduce the negative consequences associated with work-related stress.

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Statutory prevention of work injuries in Italy: an effectiveness evaluation with interrupted time series analysis in a sample of 5000 manufacturing plants from the Veneto region

Objectives

According to Italian law, prevention of injuries in the workplace falls under the National Health System Service of Prevention, Health and Safety at Work (SPISAL). In a sample of about 5000 industrial firms in the Veneto region (North-Eastern Italy), the study examines the impact of SPISAL safety programmes on injuries.

Methods

The study is based on the before-and-after comparison of injury rates in 795 industrial settings that were subject to SPISAL interventions and 4186 reference firms, which were all manufacturing industries with >10 employees; construction companies were excluded. The time window (2001–2007) was chosen in order to have 8 quarters of observation before and 8 after the intervention. The National Institute for Workers’ Compensation provided data on injuries and plants, while SPISAL gave information on interventions carried out. The preintervention and postintervention rates of injuries were compared by means of interrupted time series analyses, estimating the rate ratio (RR) with a 95% CI.

Results

Inspection after injury reduced by 24% (RR=0.76; 95% CI 0.65 to 0.90; p=0.001) all injuries, and by 36% (RR=0.64; 95% CI 0.50 to 0.83; p=0.001) severe injuries (fatalities, lost workdays >30, degree of permanent disability >0). These changes occurred immediately and persisted for 2 years. The effects of programmed inspections were never significant.

Conclusions

It can be presumed that, after a severe injury, the employees raised their standard of what they considered good work safety and, at the same time, the employers were pushed to improve the work environment as a result of the sudden attention from the workplace hygiene and safety authority and court authority. Inspection after injury was an effective strategy; however, confirmatory evidence is needed.

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Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden

Background

We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.

Methods

Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.

Results

Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).

Conclusions

The approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.

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Incidence rates of occupational diseases in the Dutch construction sector, 2010-2014

Objective

To estimate incidence and trends in incidence of occupational diseases (ODs) in the Dutch construction sector.

Methods

In a dynamic prospective cohort over a 5-year period (2010–2014), ODs assessed by occupational physicians (OPs) participating in a voluntary construction workers health surveillance (WHS) were reported to the Netherlands Centre for Occupational Diseases (NCOD). ODs were defined as a disease with a specific clinical diagnosis (International Classification of Diseases) that was predominantly caused by work-related factors as assessed by an OP. Annual incidences were determined for the total number of ODs and six frequently occurring OD groups. Trends in incidence were estimated using a multilevel negative binominal regression model.

Results

In 2014 the incidence of all OD was 12 964 per 100 000 workers and there was no significant change in incidence between 2010 and 2014 (3%; 95% CI –2% to +9%). Hearing loss (8125 per 100 000 workers) and musculoskeletal disorders (2081 per 100 000 workers) were the most frequently occurring ODs. Noise-induced hearing loss (+7%; 95% CI 1% to 13%) and contact dermatitis (+19%; 95% CI 6% to 33%) showed increasing trends. There was no statistically significant change in the incidence of low back pain, arthrosis, repetitive strain injuries, distress/burnout and chronic obstructive pulmonary disease/asthma.

Conclusions

In total, 13% of workers participating in WHS in the Dutch construction industry during 2014 had an OD diagnosed and reported by an OP. Over a 5-year period the annual incidence of reported ODs showed a statistically non-significant increase. Incidences in noise-induced hearing loss and contact dermatitis showed statistically significant increasing trends, 7% and 19%, respectively.

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Setting new standards for epidemiological research on mesothelioma

The paper by Gilham et al1 is important for a number of methodological and substantive reasons, and contributes novel information on the body of epidemiology evidence on the association between asbestos exposure and subsequent risk of pleural mesothelioma.

The use of lung fibre burden as a method to estimate past asbestos exposure has been advocated for a long time,2 and these authors have, for the first time, applied this approach to their large-scale population study, which has already provided important results on the association between asbestos and mesothelioma, based on conventional epidemiological indicators of exposure, that is, occupational categories and time-related factors.3 The method is not free from possible bias, in particular resulting from the difficulty in obtaining lung tissue samples from unbiased groups of mesothelioma cases and controls. In the study by Gilham et al, samples were analysed for 134 cases, which...

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Heat effects among migrant and seasonal farmworkers: a case study in Colorado

Background

Although migrant and seasonal farmworkers are highly vulnerable to ambient heat because of their working conditions, heat effects in this population have been rarely studied.

Objectives

We estimated effects of heat on mean daily counts of clinic visits among migrant and seasonal farmworkers by taking advantage of a unique longitudinal medical records database in the USA.

Methods

We compiled a daily weather and clinic visit data set based on data from a health centre in Colorado for the summer of 2013. A total of 14 481 patients were included in our analysis, including 150 migrant farmworkers and 231 seasonal farmworkers with an average of 3 and 4 visits per day. We used Poisson regression to estimate the associations between heat and daily all-cause or cardiovascular-specific clinic visits among migrant or seasonal farmworkers or other stratified patients. We defined heat effects as the percentage difference in average daily counts of clinic visits, comparing 90–50th centiles of daily mean apparent temperature, a composite index accounting for both temperature and humidity. We conducted a sensitivity analysis to evaluate the impact of adjustment for ozone levels and different heat definitions.

Results

Estimates of heat effects on average daily clinic visits among migrant farmworkers were positive (88.0%, 95% CI: 26.2% to 180.0%). We did not observe statistically significant associations between heat and clinic visits among other stratified groups.

Conclusions

Our study appears to be the first to link heat effects with clinic data among migrant and seasonal farmworkers. This research suggests possible significant impact of heat on migrant farmworkers and provides justifications for further studies.

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Mortality rates by occupation in Korea: a nationwide, 13-year follow-up study

Objective

The present study sought to identify inequalities in cause-specific mortality across different occupational groups in Korea.

Methods

The cohort included Korean workers enrolled in the national employment insurance programme between 1995 and 2000. Mortality was determined by matching death between 1995 and 2008 according to a nationwide registry of the Korea National Statistical Office. The cohort was divided into nine occupational groups according to the Korean Standard Occupational Classification (KSOC). Age-standardised mortality rates of each subcohort were calculated.

Results

The highest age-standardised mortality rate was identified in KSOC 6 (agricultural, forestry and fishery workers; male (M): 563.0 per 100 000, female (F): 206.0 per 100 000), followed by KSOC 9 (elementary occupations; M: 499.0, F: 163.4) and KSOC 8 (plant, machine operators and assemblers; M: 380.3, F: 157.8). The lowest rate occurred in KSOC 2 (professionals and related workers; M: 209.1, F: 93.3). Differences in mortality rates between KSOC 2 and KSOC 9 (M: 289.9, F: 70.1) and the rate ratio of KSCO9 to KSCO2 (M: 2.39, F: 1.75) were higher in men. The most prominent mortality rate difference was observed in external causes of death (M: 96.9, F: 21.6) and liver disease in men (38.3 per 100 000). Mental disease showed the highest rate ratio (M: 6.31, F: 13.00).

Conclusions

Substantial differences in mortality rates by occupation were identified. Main causes of death were injury, suicide and male liver disease. Development of policies to support occupations linked with a lower socioeconomic position should be prioritised.

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Hepatitis C ups risk of head, neck cancers - Times of India

Times of India

Hepatitis C ups risk of head, neck cancers
Times of India
Also paramount to the research, said Torres, was to control for smoking, a major risk factor for head and neck cancers. Therefore, they identified 694 control subjects, all with a diagnosis of smoking-related cancers (378 with lung, 168 with esophageal ...
Head and Neck Cancers May Be Linked to Hepatitis CPhilly.com
MD Anderson links hepatitis C to greater risk of head and neck cancersHouston Chronicle

all 4 news articles »

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HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators in governing fundamental biological processes, as well as in tumorigenesis. The nuclear paraspeckle assembly transcript 1 (NEAT1) is one of the most highly regulated lncRNAs in recent genomic datasets, however, its biological role and regulatory mechanism in ovarian cancer (OC) development and progression are poorly defined. In this study, we identified that NEAT1 was up-regulated in OC patients and cell lines, and its expression was associated with the FIGO stage and lymph node metastasis. Furthermore, the ectopic expression of NEAT1_1 in OVCAR-3 cell lines promoted cell proliferation and invasion, whereas knockdown of NEAT1_1 did the opposite. Furthermore, NEAT1_1 was stabilized by an RNA-binding protein HuR, but suppressed by miR-124-3p in OC cells. Accordingly, the increased HuR mRNA and decreased miR-124-3p levels were observed in OC patients. These results suggested that lncRNA NEAT1, whose expression was collaboratively controlled by HuR and miR-124-3p, could regulate ovarian carcinogenesis and may serve as a potential target for antineoplastic therapies.

LncRNA NEAT1, whose expression was collaboratively controlled by HuR and miR-124-3p, could regulate ovarian carcinogenesis and may serve as a potential target for antineoplastic therapies.

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A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors

Abstract

Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open-label, phase I study of the fully human anti-ALK-1 mAb PF-03446962 conducted in Japan and South Korea, in Asian patients with advanced solid tumors. The dose escalation Part 1 of the study was based on a standard 3 + 3 design (n = 16). In Part 2, patients were treated with PF-03446962 at 7 and 10 mg/kg (10/cohort), including patients with disease progression following prior VEGF receptor (R)-targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-03446962. No dose-limiting toxicity (DLT) was noted in the 12 DLT-evaluable patients. Treatment was well tolerated. The MTD for biweekly intravenous administration was estimated to be 10 mg/kg and the RP2D 7 mg/kg. Treatment-related grades 1–3 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment-related AEs were grades 1–2 pyrexia and epistaxis. Four patients (3/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK-1 inhibition by PF-03446962. Stable disease for 12 weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK-1 inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF(R)-targeted inhibitors or chemotherapy.

This report presents the safety, preliminary activity, and pharmacokinetics results of the first study of the novel anti-activin receptor-like kinase 1 (ALK-1) monoclonal antibody PF-03446962 in Asian patients with advanced solid tumors. The study findings suggest that activin receptor-like kinase-1 (ALK-1) inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies, complementary to vascular endothelial growth factor (receptor)-targeted therapy or chemotherapy.

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Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma

Abstract

Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen (HLA) genetic variation, could influence host risk of hepatocellular carcinoma (HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 (PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression quantitative trait loci (eQTL) for PTPN12 by bioinformatics analyses. In this study, we genotyped the PTPN12 eQTL and sequenced the HBV region EnhII/BCP/PC in a case–control cohort including 1507 HBV-related HCC cases and 1560 HBV persistent carriers as controls. The variant genotype GG of rs11489585 increased HCC risk compared to the HBV persistent carriers (adjusted OR = 2.03, 95% confidence interval [CIs] = 1.30–3.18). We also detected borderline significant associations of PTPN12 eQTL rs11489585 with HBV mutations (P = 0.05 for G1799C). Taken together, PTPN12 may influence HCC risk accompanied by HBV mutations.

PTPN12 may influence HCC risk accompanied by HBV mutations.

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Πληροφορίες

Πέμπτη 14 Απριλίου 2016

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