Sleep-related problems and minor psychiatric disorders among Brazilian shift workers.

Sleep-related problems and minor psychiatric disorders among Brazilian shift workers.

Psychiatry Res. 2017 Aug 14;257:412-417

Authors: Olinto MTA, Garcez A, Henn RL, Macagnan JBA, Paniz VMV, Pattussi MP

Abstract
The aim of this study was to explore the association between sleep-related problems with the occurrence of minor psychiatric disorders in shift workers of southern Brazil. A cross-sectional study with 1202 workers (785 females) aged 18-50 years was carried out. Minor psychiatric disorders were assessed using the Self-Reporting Questionnaire (SRQ-20), and four sleep problems were collected and analyzed: sleep deprivation (≤ 5h), difficulty falling asleep, waking up during sleep, and sleep medication use. Results show that the overall prevalence of minor psychiatric disorders was 26.8%, but it was more prevalent among females than males (30.2% vs. 20.4%). Nightshift work was significantly associated with the occurrence of sleep-related problems. After adjusting for confounding factors, the number of sleep-related problems showed a positive linear trend with psychiatric disorders in both sexes. Having two or more sleep-related problems was associated with increased probability of psychiatric disorders approximately three-fold among males and two-fold among females, when compared with those without sleep problems. In conclusion, this study demonstrated that sleep-related problems have a strong and independent association with psychiatric disorders among shift workers. Furthermore, the prevalence of both conditions was higher among females than males; however, the strength of these associations was higher in males.

PMID: 28837929 [PubMed - as supplied by publisher]

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Reply: Unilateral Pulmonary Edema after Visiting High Altitude.

Reply: Unilateral Pulmonary Edema after Visiting High Altitude.

Ann Am Thorac Soc. 2017 Aug 24;:

Authors: Cherian SV, Estrada-Y-Martin RM

Abstract
N/A.

PMID: 28837781 [PubMed - as supplied by publisher]

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National estimates of 30-day readmissions among children hospitalized for asthma in the United States.

National estimates of 30-day readmissions among children hospitalized for asthma in the United States.

J Asthma. 2017 Aug 24;:0

Authors: Veeranki SP, Ohabughiro MU, Moran J, Mehta HB, Ameredes BT, Kuo YF, Calhoun WJ

Abstract
Objective Previous single-center studies have reported that up to 40% of children hospitalized for asthma will be readmitted. The study objectives are to investigate the prevalence and timing of 30-day readmissions in children hospitalized with asthma, and to identify factors associated with 30-day readmissions. Methods Data (n = 12,842) for children aged 6-18 years hospitalized for asthma were obtained from the 2013 Nationwide Readmission Database (NRD). The primary study outcome was time to readmission within 30 days after discharge attributable to any cause. Several predictors associated with risk of admission were included: patient (age, sex, median household income, insurance type, county location, pediatric chronic complex condition), admission (type, day, emergency services utilization, length of stay (LOS), discharge disposition) and hospital (ownership, bed size, teaching status). Cox's Proportional Hazards model was used to identify predictors. Results Of 12,842 asthma-related index hospitalizations, 2.5% were readmitted within 30 days post discharge. Time to event models identified significantly higher risk of readmission among asthmatic children aged 12-18 years, those who resided in in micropolitan counties, those with >4 days LOS during index hospitalization, those who were hospitalized in urban hospital, who had unfavorable discharge (HR 2.53, 95% CI 1.33-4.79), and those who were diagnosed with PCCC, respectively than children in respective referent categories. Conclusion A multi-dimensional approach including effective asthma discharge action plans and follow-up processes, home-based asthma education, and neighborhood/community-level efforts to address disparities should be integrated into routine clinical care of asthma children.

PMID: 28837382 [PubMed - as supplied by publisher]

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Family-based childhood obesity prevention interventions: a systematic review and quantitative content analysis.

Family-based childhood obesity prevention interventions: a systematic review and quantitative content analysis.

Int J Behav Nutr Phys Act. 2017 Aug 24;14(1):113

Authors: Ash T, Agaronov A, Young T, Aftosmes-Tobio A, Davison KK

Abstract
BACKGROUND: A wide range of interventions has been implemented and tested to prevent obesity in children. Given parents' influence and control over children's energy-balance behaviors, including diet, physical activity, media use, and sleep, family interventions are a key strategy in this effort. The objective of this study was to profile the field of recent family-based childhood obesity prevention interventions by employing systematic review and quantitative content analysis methods to identify gaps in the knowledge base.
METHODS: Using a comprehensive search strategy, we searched the PubMed, PsycIFO, and CINAHL databases to identify eligible interventions aimed at preventing childhood obesity with an active family component published between 2008 and 2015. Characteristics of study design, behavioral domains targeted, and sample demographics were extracted from eligible articles using a comprehensive codebook.
RESULTS: More than 90% of the 119 eligible interventions were based in the United States, Europe, or Australia. Most interventions targeted children 2-5 years of age (43%) or 6-10 years of age (35%), with few studies targeting the prenatal period (8%) or children 14-17 years of age (7%). The home (28%), primary health care (27%), and community (33%) were the most common intervention settings. Diet (90%) and physical activity (82%) were more frequently targeted in interventions than media use (55%) and sleep (20%). Only 16% of interventions targeted all four behavioral domains. In addition to studies in developing countries, racial minorities and non-traditional families were also underrepresented. Hispanic/Latino and families of low socioeconomic status were highly represented.
CONCLUSIONS: The limited number of interventions targeting diverse populations and obesity risk behaviors beyond diet and physical activity inhibit the development of comprehensive, tailored interventions. To ensure a broad evidence base, more interventions implemented in developing countries and targeting racial minorities, children at both ends of the age spectrum, and media and sleep behaviors would be beneficial. This study can help inform future decision-making around the design and funding of family-based interventions to prevent childhood obesity.

PMID: 28836983 [PubMed - in process]

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Pain, Bullying Involvement, and Mental Health Problems Among Children and Adolescents With ADHD in Taiwan.

Pain, Bullying Involvement, and Mental Health Problems Among Children and Adolescents With ADHD in Taiwan.

J Atten Disord. 2017 Aug 01;:1087054717724514

Authors: Yeh YC, Huang MF, Wu YY, Hu HF, Yen CF

Abstract
OBJECTIVE: The aim of this study was to examine the relationships of pain and pain-induced functional impairment with bullying involvement, as well as the relationships between pain and mental health problems among 474 children and adolescents with ADHD.
METHOD: The levels of pain, pain-induced functional impairment, involvement in bullying, depression, anxiety, ADHD symptoms, and sleep quality were assessed.
RESULTS: Both victims of verbal and relational bullying and victims of physical bullying were more likely to have pain and pain-induced functional impairment than nonvictims. The perpetrators of verbal and relational bullying were more likely to have pain than the nonperpetrators. Participants with pain and pain-induced functional impairment experienced more severe depression and anxiety and worse sleep quality than did those without pain or pain-induced functional impairment.
CONCLUSION: Clinical and educational professionals should consider the possibility of involvement in bullying and comorbid depression, anxiety, and poor sleep quality among ADHD children and adolescents with pain problems.

PMID: 28836888 [PubMed - as supplied by publisher]

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Early intervention for bipolar disorder in adolescents: A psychosocial perspective.

Related Articles

Early intervention for bipolar disorder in adolescents: A psychosocial perspective.

Early Interv Psychiatry. 2017 Aug 23;:

Authors: McAulay C, Mond J, Touyz S

Abstract
AIM: Early intervention in bipolar disorder (BD) has received increasing attention in recent years. The identification of risk factors has improved, but researchers continue to struggle to find an effective treatment once the illness has become established. The aetiology of BD and feasibility of early intervention present a challenge, making it difficult to decide who to target, as well as how.
METHODS: This essay seeks to address the lack of guidance for managing patients with a possible emerging bipolar illness, by presenting a rough roadmap to psychological care. The psychological techniques currently showing the most potential for this challenging group are reviewed. Markers of risk and supplementary clinical targets, such as anxiety and sleep disruption, are also discussed.
RESULTS: While research in this group remains in its infancy, various avenues of enquiry show promise, such as family-based approaches, CBT that targets features beyond the core illness, psychoeducation, and interventions that consider physical health. However, clearer pathways for establishing the course and stage of the illness are required to inform the intensity and type of treatment.
CONCLUSION: It is argued that treating early, indistinct symptoms of psychological distress, that may or may not signify prodromal BD, is valuable beyond its utility as an early intervention tool, as it has the capacity to improve help-seeking behaviour, quality of life and the likelihood of functional recovery in those who go on to develop the illness as adults.

PMID: 28836352 [PubMed - as supplied by publisher]

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Association between left atrial enlargement and obstructive sleep apnea in a general population of 71-year-old men.

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Association between left atrial enlargement and obstructive sleep apnea in a general population of 71-year-old men.

J Sleep Res. 2017 Aug 24;:

Authors: Holtstrand Hjälm H, Fu M, Hansson PO, Zhong Y, Caidahl K, Mandalenakis Z, Morales D, Ergatoudes C, Rosengren A, Grote L, Thunström E

Abstract
Left atrial enlargement has been shown to be associated with obstructive sleep apnea in patients with coronary artery disease and in sleep clinic cohorts. However, data from the general population are limited. The aim of this study was to investigate whether there is an association between obstructive sleep apnea and left atrial enlargement in a random sample from a general population of 71-year-old men. As part of the longitudinal population study The Study of Men Born in 1943, we analysed cross-sectional data for 411 men, all 71 years old, who had participated in an overnight home sleep study and a standardized echocardiographic examination. Of the 411 men, 29.4% had moderate to severe obstructive sleep apnea [apnea-hypopnea index score of ≥15 (n = 121)]. These participants showed a significantly higher frequency of systolic heart failure, hypertension, overweight, had greater waist circumference as well as higher left atrial areas compared with men with no or mild obstructive sleep apnea (23.7 ± 5.5 cm(2) versus 21.6 ± 4.5 cm(2) , P < 0.001). In a linear regression analysis, obstructive sleep apnea was significantly associated with left atrial enlargement after adjusting for overweight, atrial fibrillation, heart failure with reduced ejection fraction, hypertension and mitral regurgitation. Compared with individuals without obstructive sleep apnea, the mean left atrial area was 1.7 ± 1.5 cm(2) larger in men with severe obstructive sleep apnea (P < 0.05) and 1.3 ± 1.1 cm(2) larger among men with moderate obstructive sleep apnea (P < 0.05). In this cross-sectional study of 71-year-old men from the general population, left atrial area was independently associated with prevalence and severity of obstructive sleep apnea.

PMID: 28836321 [PubMed - as supplied by publisher]

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Association Between Spousal Caregiver Well-Being and Care Recipient Healthcare Expenditures.

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Association Between Spousal Caregiver Well-Being and Care Recipient Healthcare Expenditures.

J Am Geriatr Soc. 2017 Aug 24;:

Authors: Ankuda CK, Maust DT, Kabeto MU, McCammon RJ, Langa KM, Levine DA

Abstract
OBJECTIVES: To measure the association between spousal depression, general health, fatigue and sleep, and future care recipient healthcare expenditures and emergency department (ED) use.
DESIGN: Prospective cohort study.
SETTING: Health and Retirement Study.
PARTICIPANTS: Home-dwelling spousal dyads in which one individual (care recipient) was aged 65 and older and had one or more activity of daily living or instrumental activity of daily living disabilities and was enrolled in Medicare Part B (N = 3,101).
EXPOSURE: Caregiver sleep (Jenkins Sleep Scale), depressive symptoms (Center for Epidemiologic Studies Depression-8 Scale), and self-reported general health measures.
MEASUREMENTS: Primary outcome was care recipient Medicare expenditures. Secondary outcome was care recipient ED use. Follow-up was 6 months.
RESULTS: Caregiver depressive symptoms score and six of 17 caregiver well-being measures were prospectively associated with higher care recipient expenditures after minimal adjustment (P < .05). Higher care recipient expenditures remained significantly associated with caregiver fatigue (cost increase, $1,937, 95% confidence interval (CI) = $770-3,105) and caregiver sadness (cost increase, $1,323, 95% CI = $228-2,419) after full adjustment. Four of 17 caregiver well-being measures, including severe fatigue, were significantly associated with care recipient ED use after minimal adjustment (P < .05). Greater odds of care recipient ED use remained significantly associated with caregiver fatigue (odds ratio (OR) = 1.24, 95% CI = 1.01-1.52) and caregiver fair to poor health (OR = 1.23, 95% CI = 1.04-1.45) after full adjustment. Caregiver total sleep score was not associated with care recipient outcomes.
CONCLUSION: Poor caregiver well-being, particularly severe fatigue, is independently and prospectively associated with higher care recipient Medicare expenditures and ED use.

PMID: 28836269 [PubMed - as supplied by publisher]

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Effect of atopic dermatitis on quality of life and its psychosocial impact in Asian adolescents.

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Effect of atopic dermatitis on quality of life and its psychosocial impact in Asian adolescents.

Australas J Dermatol. 2017 Aug 24;:

Authors: Ng MS, Tan S, Chan NH, Foong AY, Koh MJ

Abstract
BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a common condition affecting up to 20% of the paediatric population in Singapore. It is often associated with significant psychosocial morbidity and can affect patients' quality of life (QOL) tremendously. This study investigated the varying lifestyle impacts, and psychosocial domains most affected by AD in adolescent children in Singapore.
METHODS: A prospective study evaluating the impact of AD on the QOL of adolescents was conducted over a 6-month period from July to December 2014. Adolescents aged 11-16 years with varying eczema severity were recruited. Eczema severity was determined by using the eczema area and severity index (EASI) scores. Lifestyle impact of AD was evaluated using patient-reported children's dermatology life quality index (CDLQI) scores. Statistical analysis was performed using an analysis of one-way variance and Student's t-test.
RESULTS: A total of 50 patients were enrolled and divided into three groups: mild (<10.3), moderate (10.3-20.9) and severe (>20.9) eczema based on EASI scores. Patients with mild and moderate eczema had lower CDLQI scores. Adolescents were most affected by the disruption that their symptoms had on their leisure and physical activities and sleep as a result of itch and scratching, respectively.
CONCLUSION: Chronic sufferers of severe eczema experience poorer QOL than those with mild or moderate eczema. They also experience significant psychosocial impact as a consequence of their condition.

PMID: 28836265 [PubMed - as supplied by publisher]

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Postoperative Blutdruckschwankungen nach Karotisendarteriektomie

Zusammenfassung

Hintergrund

Postoperative Blutdruckschwankungen nach Karotisendarteriektomie (CEA) sind bekannte Faktoren für ein erhöhtes Morbiditäts- und Mortalitätsrisiko.

Ziel der Arbeit

Darstellung des Einflusses der zwei etablierten gefäßchirurgischen Rekonstruktionsverfahren, der Eversions-CEA (E-CEA) und der konventionellen CEA mit Patchplastik (K-CEA), sowie der neueren sinuserhaltenden Eversions-CEA (SE-E-CEA) auf die postoperative Hämodynamik unter Berücksichtigung bisheriger wissenschaftlicher Erkenntnisse.

Material und Methoden

Auswertung klinisch-wissenschaftlicher Evidenz aus der PubMed (NLM) -Datenbank zu der jeweiligen Operationstechnik aus dem Zeitraum 1974 bis 2017 unter Ausschluss von Fallberichten.

Ergebnisse

Insgesamt wurden 34 Literaturstellen sowie eine Metaanalyse identifiziert, die sich mit der beschriebenen Thematik wissenschaftlich auseinandersetzen. Die Ergebnisse der Studien sowie der Metaanalyse zeigen, dass die E‑CEA mit einer Beeinträchtigung der lokalen Barorezeptorfunktion und einem erhöhten Bedarf an Vasodilatatoren in der frühen postoperativen Phase vergesellschaftet ist, wohingegen die K‑CEA und SE-E-CEA einen günstigeren Effekt auf den postoperativen Blutdruck auszuüben scheinen.

Schlussfolgerung

Unabhängig von der angewendeten Operationstechnik übt die CEA einen direkten Einfluss auf die Regulation des Blutdrucks aus. Eine engmaschige Überwachung des Blutdrucks sollte zumindest im postoperativen stationären Verlauf stattfinden. Der Stellenwert der SE-E-CEA als Alternative zu der klassischen E‑CEA muss zunächst ausführlicher wissenschaftlich untersucht werden.

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Minimalinvasive und roboterassistierte Chirurgie bei zystischen Pankreastumoren

Zusammenfassung

Hintergrund

Die Indikationsstellung zur chirurgischen Resektion zystischer Pankreastumoren ist komplex und das operative Risiko für den Patienten muss häufig gegenüber dem Risiko einer malignen Entartung abgewogen werden. Ziel der Arbeit ist ein Überblick über die Ergebnisse der minimalinvasiven Operationstechniken bei zystischen Pankreastumoren.

Methoden

Es erfolgte eine orientierende, systematische Literatursuche unter Verwendung der Medline-Datenbank (PubMed) sowie eine selektive Übersichtsdarstellung.

Ergebnisse

Es liegen bisher keine randomisierten kontrollierten Studien zum Vergleich der offenen und minimalinvasiven Resektion zystischer Tumoren vor. Retrospektive Fallserien bescheinigen den minimalinvasiven Techniken die Machbarkeit und Sicherheit sowie eine vergleichbare Morbidität nach distaler Pankreatektomie (DP), Pankreatoduodenektomie (PD), zentraler (CP) und totaler Pankreatektomie sowie der Enukleation. Während die meisten DP laparoskopisch durchgeführt werden, ist die Erfahrung für die minimalinvasive PD mit dem Roboter größer, jedoch auf wenige spezialisierte Zentren verteilt. Insgesamt ist die Zahl der publizierten Fälle minimalinvasiver organsparender Pankreasresektionen (CP oder Enukleation) bei zystischen Tumoren sehr gering; die verfügbaren selektionierten Ergebnisse jedoch zunächst positiv.

Diskussion

Die minimalinvasive Chirurgie bei zystischen Pankreastumoren hat das Potenzial, das operative Trauma der Patienten bei gleichen oder geringeren Komplikationsraten zu reduzieren. Voraussetzung ist eine zunehmende Spezialisierung insbesondere bei komplexen Operationen. Bei diesen Eingriffen wird der klinische Einsatz des Roboters ansteigen. Eine prospektive Dokumentation der Ergebnisse ist im Rahmen der Qualitätssicherung anzustreben.

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Resektion von Hauptgang- und Mischtyp-IPMN ≥5 mm

Zusammenfassung

Durch den Fortschritt in der Bildgebung werden immer mehr zystische Pankreasläsionen zufällig diagnostiziert. Unter den zystischen Pankreasläsionen nehmen dabei intraduktale papillär-muzinöse Neoplasien (IPMN) aufgrund ihres malignen Entartungspotenzials immer mehr eine wichtigere Rolle ein und die weitere Therapie bzw. Resektion muss sorgfältig abgewogen werden. Für die Diagnostik sollte stets eine Schnittbildgebung wie Computertomographie (CT) und/oder Magnetresonanztomographie (MRT) mit MR-Cholangiopankreatikographie (MRCP) durchgeführt werden. Ergänzend sollte eine Endosonographie (EUS) mit Punktion der zystischen Raumforderung erfolgen. Die Punktionsanalyse von Biomarkern wie GNAS- sowie KRAS-Mutationen oder das Verhältnis von Neutrophilen zu Lymphozyten (NLR) kann zur Differenzialdiagnose eingesetzt werden; diese spielen beim Hauptgang- und Mischtyp-IPMN derzeit jedoch noch eine untergeordnete Rolle. Die aktuellen Leitlinien (Fukuoka- und EU-Leitlinie) empfehlen beim Hauptgang- und Mischtyp-IPMN eine Resektion nach onkologischen Standards. Der Cut-off der Hauptgangdilatation liegt derzeit zwischen 5–10 mm, wird jedoch in den neusten Studien auf ≥5 mm reduziert, um einer potenziellen malignen Transformation vorzugreifen. Patientenalter und Komorbiditäten sind wichtige Parameter, welche bei der Interventionsentscheidung eine gewichtige Rolle spielen. Bei der Resektion sollten intraoperative Schnellschnittuntersuchungen des Gangepithels durchgeführt werden, um im Falle einer High-grade-Dysplasie im Absetzungsrand eine Nachresektion durchzuführen. Die Überwachung sollte bei potenziellen Risikokandidaten in regelmäßigen Abständen von 6 bis 12 Monaten erfolgen. Patienten mit malignem IPMN sollten analog zum Pankreaskarzinom nachgesorgt werden. Ein Screening für extrapankreatische Karzinome ist beim IPMN nicht erforderlich.

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Effects of different fertilizers on growth and nutrient uptake of Lolium multiflorum grown in Cd-contaminated soils

Abstract

This study aimed to explore the effects of different fertilizers and their combinations on growth and nutrient and Cd uptake of Lolium multiflorum. Compared with control treatment, chemical fertilizer, organic manure, and their conjunctions with biofertilizer increased shoot biomass. Biofertilizers were found to cause significant reductions in shoot biomass of plants grown in organic manure-treated and control soil. Decreased soil-available N and P and shoot N and K concentrations in biofertilizer amendment treatments indicated that plant growth and nutrient absorption might be negatively affected under nutrient deficiency conditions. Elevated shoot biomasses contributed to the highest shoot Cd contents in chemical fertilizer and chemical fertilizer + biofertilizer treatments among all treatments. But the maximum translocation efficiency occurred in biofertilizer + chemical fertilizer + organic manure treatment, followed by organic manure and chemical fertilizer + organic manure treatments. Based on the results, we can conclude that the application of only the biofertilizer Bacillus subtilis should be avoided in nutrient-limited soils. Chemical fertilizer application could benefit the amount of Cd in shoots, and organic manure application and its combinations could result in the higher translocation efficiency.

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Reductive precipitation and removal of Cr(VI) from groundwaters by pipe flocculation-microfiltration

Abstract

Chromium (Cr(VI)) is a very toxic and carcinogenic element, which is widely present in groundwaters, mainly due to geogenic conditions. The limit of Cr(VI) in drinking water is expected to be reduced to 10 μg/L in both the USA and the European Union. Recent literature findings indicated that the most efficient process in reducing Cr(VI) levels to below 10 μg/L proved to be Cr(VI) reduction by Fe(II), by applying a molar ratio Fe(II)/Cr(VI) of around 9. In the present work, we investigated the reduction of Cr(VI) by Fe(II) in pipe flocculation reactors followed by filtration of insoluble products by microfiltration. The proposed technology involves re-circulation of a part of the sludge in the pipe reactors, in order to improve kinetics and efficiency of the process. The obtained results showed that with a Fe(II) dose of around 1 mg/L, Cr(VI) was reduced to below 10 μg/L, by even an initial concentration as high as 300 μg/L of Cr(VI), corresponding to a molar ratio Fe(II)/Cr(VI) of around 3, thus reducing the overall quantity of reductive reagents and of the produced sludge. This ratio was also confirmed by the XPS analysis, which also showed that Cr(VI) was reduced to Cr(III) and then precipitated either as Cr(OH)₃ or associated with the produced iron oxides.

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The Spanish version of the Patient-Rated Wrist Evaluation outcome measure: cross-cultural adaptation process, reliability, measurement error and construct validity

The Patient-Rated Wrist Evaluation (PRWE) is a widely used measure of patient-reported disability and pain related to wrist disorders. We performed cross-cultural adaptation of the PRWE into Spanish (Spain) an...

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Benefits of different intensity of aerobic exercise in modulating body composition among obese young adults: a pilot randomized controlled trial

The aim of present study was to compare the effects of different aerobic exercise intensities and energy expenditures on the body composition of sedentary obese college students in Taiwan.

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Evaluation of PDQ-8 and its relationship with PDQ-39 in China: a three-year longitudinal study

Parkinson's disease is characterized by motor and non-motor symptoms with wide ranging impacts on the health-related quality of life. The 39-item Parkinson's disease Questionnaire (PDQ-39) is the most widely u...

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Production of a fermented organic rice syrup with higher isomalto-oligosaccharide using Lactobacillus plantarum

Abstract

Isomalto-oligosaccharide (IMO) syrup was prepared from organic rice, in which Lactobacillus plantarum as a starter was inoculated to raise its purity and also produce a fermented rice beverage. Of the five strains of lactic acid bacteria tested, L. plantarum was preferentially selected in terms of a viable cells (7.3 × 10⁸ colony forming unit (CFU/mL) and higher dry cell weight (13 mg/mL). The fermented syrup-based medium did not affect the growth of L. plantarum. As expected, the residual sugar content gradually decreased by 1.34% compared with the initial concentration. It was apparent that the residual sugars but not oligosaccharides were removed during the L. plantarum fermentation period. The production of lactic acid was the highest (8125.78 mg/kg) among the organic acids produced in the fermented IMO syrup.

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Stationary phase-dependent accumulation of ectoine is an efficient adaptation strategy in Vibrio anguillarum against cold stress

Publication date: December 2017
Source:Microbiological Research, Volume 205
Author(s): Yue Ma, Qiyao Wang, Wensheng Xu, Xiaohong Liu, Xiating Gao, Yuanxing Zhang
The capability of cold-adaptation is a prerequisite of microorganisms that survive in an environment with frequent fluctuations in temperature. As a global causative agent of vibriosis in marine fish farming, Vibrio anguillarum can efficiently grow and proliferate under cold-stress conditions, which is 15°C lower than the optimal growth temperatures (25–30°C). Our data showed that V. anguillarum was able to synthesize ectoine de novo and that ectoine was essential for its growth under cold stress. Using ¹H nuclear magnetic resonance spectroscopy and mutants lacking ectABC and proVWX (ectoine synthesis and transporter system genes, respectively), we confirmed that accumulation of this compatible solute occurs strictly at low temperatures and that the expression of ectA and proV is highly activated in the stationary growth phase. However, the synthesis of ectoine was repressed by exogenous choline (precursor of glycine betaine), suggesting that ectoine is an alternative compatible solute as a cold-stress protectant in V. anguillarum. Based on these results, we present possible scenarios of the synthesis and uptake of ectoine, which will facilitate the understanding of the molecular mechanism of V. anguillarum adaptation to cold environments and help improve freezing-dry processes for the V. anguillarum live vaccine.



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Analysis of the Pho regulon in Streptomyces tsukubaensis

Publication date: Available online 24 August 2017
Source:Microbiological Research
Author(s): María Ordóñez-Robles, Fernando Santos-Beneit, Antonio Rodríguez-García, Juan F. Martín
Phosphate regulation of antibiotic biosynthesis in Streptomyces has been studied due to the importance of this genus as a source of secondary metabolites with biological activity. Streptomyces tsukubaensis is the main producer of tacrolimus (or FK506), an immunosuppressant macrolide that generates important benefits for the pharmaceutical market. However, the production of tacrolimus is under a negative control by phosphate and, therefore, is important to know the molecular mechanism of this regulation. Despite its important role, there are no reports about the Pho regulon in S. tsukubaensis. In this work we combined transcriptional studies on the response to phosphate starvation with the search for PHO boxes in the whole genome sequence of S. tsukubaensis. As a result, we identified a set of genes responding to phosphate starvation and containing PHO boxes that include common Pho regulon members but also new species-specific candidates. In addition, we demonstrate for the first time the functional activity of PhoP from S. tsukubaensis through complementation studies in a Streptomyces coelicolor ΔphoP strain. For this purpose, we developed an anhidrotetracycline inducible system that can be applied to the controlled expression of target genes.



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Implementation of a perioperative surgical home protocol for pediatric patients presenting for adenoidectomy

Publication date: October 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 101
Author(s): Vidya T. Raman, Dmitry Tumin, Joshua Uffman, Arlyne K. Thung, Candice Burrier, Kris R. Jatana, Charles Elmaraghy, Joseph D. Tobias
IntroductionThe perioperative surgical home (PSH) is a patient-centered model designed to improve health, streamline the delivery of health care, and reduce the cost of care. Following the national introduction of PSH in 2014 by the ASA, adult hospitals have reported success with this model, with studies validating the benefits of PSH including reducing length of stay, lowering costs, and improving patient satisfaction.MethodsEligible patients, ranging in age from 16-35 months of age, were identified by the pre-admission testing (PAT) registered nurses (RNs) and faculty anesthesiologists upon review of the patient history. Participation in Pediatric PSH (PPSH) was introduced to the families by the pediatric otolaryngologists. Either the patient's family or physician team could elect to decline participation in the PPSH model. On the day of surgery, the PPSH protocol included a paper checklist to ensure that all patients met eligibility standards. A standardized order-set was implemented in the electronic medical record (EMR) for pre-operative and post-operative nursing instructions and eligible medications. Patients received at least 3 hours of postoperative monitoring prior to discharge home to address postoperative issues. Prior to discharge, caregivers watched a standard teaching video, available on YouTube, which was developed in conjunction with the hospital educational and technical support staff. An attending anesthesiologist made a postoperative followup phone call on the evening of surgery to ensure no untoward events were experienced by the patient as well as elicit caregiver feedback concerning the discharge process. The protocol was discontinued if at any time family members, physicians, or nurses were uncomfortable with completing the protocol or felt that the patient did not meet discharge criteria.ResultsOne hundred sixty-six patients were evaluated for PPSH inclusion. Forty patients were excluded (23 did not meet inclusion criteria, 5 had viral upper respiratory infections, and 10 for other non specified reasons such as tonsillectomy added, sibling with surgery, and incorrect documentation). Therefore, a total of 126 were eligible for PPSH (male/female = 69/57; age 22 ± 4 months). The comparison group included 1,029 children (male/female = 645/384; age 22 ± 7 months of age) undergoing adenoidectomy who were not evaluated for PPSH inclusion. Of the 126 PPSH participants included in the analysis, 27 were excluded at some point during the pathway. Nine cases experienced oxygen desaturation, laryngospasm, or required supplemental oxygen. Noncompliance with the protocol was noted in 5 cases, parental concerns were noted in 17 cases, and there were concerns from the pediatric anesthesiologist or otolaryngologist in 5 cases. In the comparison group, hospital length of stay was significantly longer than in the PSH group (p<0.001), with 524 (51%) patients discharged on the day of service compared to 99 (79%) in the PSH group. No major morbidity or mortality occurred. There was no difference between the two groups in return to the emergency department (ED) visits within 30 days (PSH: 7/126, 6%; control: 59/1,029, 6%; p=0.935). Within 14 days of the procedure, 4 PPSH patients visited urgent care or a primary care physician; 4 visited the ED; and 1 was readmitted to the hospital. Twenty families contacted the otorhinolaryngology triage phone line primarily related to pain and fever.ConclusionWe present our experience and success in developing a PPSH for patients, ranging in age from 16 to 35 months of age, undergoing adenoidectomy either alone or with tympanostomy tube insertion by protocolizing care, collaborating among care providers, and educating families. With this process in place, a significant percentage of these patients who were previously admitted were discharged home the same day of surgery.



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Response to the letter by Adams and Kwee, entitled: “Unproven value of end-of-treatment FDG-PET in Hodgkin lymphoma”

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Relation between thoracic aortic inflammation and features of plaque vulnerability in the coronary tree in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. An FDG-positron emission tomography and optical coherence tomography study

Abstract

Purpose

To evaluate the relationship between aortic inflammation as assessed by ¹⁸F–fluorodeoxyglucose-positron emission tomography (¹⁸F–FDG-PET) and features of plaque vulnerability as assessed by frequency domain-optical coherence tomography (FD-OCT).

Methods

We enrolled 30 consecutive non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. All patients underwent three-vessel OCT before intervention and ¹⁸F–FDG-PET before discharge. Univariable and C-reactive protein (CRP)-adjusted linear regression analyses were performed between features of vulnerability [namely:lipid-rich plaques with and without macrophages and thin cap fibroatheromas (TCFA)] and ¹⁸F–FDG uptake in both ascending (AA) and descending aorta (DA) [measured either as averaged mean and maximum target-to-blood ratio (TBR) or as active slices (TBR_max ≥ 1.6)].

Results

Mean age was 62 years, and 26 patients were male. On univariable linear regression analysis TBR_mean and TBR_max in DA was associated with the number of lipid-rich plaques (β = 4.22; 95%CI 0.05–8.39; p = 0.047 and β = 3.72; 95%CI 1.14–6.30; p = 0.006, respectively). TBR_max in DA was also associated with the number of lipid-rich plaques containing macrophages (β = 2.40; 95%CI 0.07–4.72; p = 0.044). A significant CRP adjusted linear association between the TBR_max in DA and the number of lipid-rich plaques was observed (CRP-adjusted β = 3.58; 95%CI -0.91-6.25; p = 0.01). TBR_max in DA showed a trend towards significant CRP-adjusted association with number of lipid-rich plaques with macrophages (CRP-adjusted β = 2.30; 95%CI -0.11-4.71; p = 0.06). We also observed a CRP-adjusted (β = 2.34; 95%CI 0.22–4.47; p = 0.031) linear association between the number of active slices in DA and the number of lipid-rich plaques. No relation was found between FDG uptake in the aorta and the number of TCFAs.

Conclusions

In patients with first NSTEACS^{, 18}F–FDG uptake in DA is correlated with the number of OCT detected lipid-rich plaques with or without macrophages. This association may be independent from CRP values.

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Influence of body mass index and type of low-level exercise on the side effect profile of regadenoson

Abstract

Purpose

Regadenoson, an A_2A adenosine receptor pharmacologic stress agent for radionuclide myocardial perfusion imaging (MPI), is administered as a single, fixed dose. We studied the side effect profile of regadenoson combined with two types of low-level exercise, according to body mass index (BMI).

Methods

Three hundred and fifty-six patients (46.1% men, mean age 67.7±10.7 years, range 31–90 years) underwent regadenoson stress testing combined with low-level exercise. Subjects were classified according to BMI as normal, overweight, or obese, and the type of low-level exercise performed as walking on the treadmill (TE group, n=190) or forcefully swinging legs while sitting (SS group, n=166). Patients' demographics, medical history, clinical symptoms during stress, changes in ECG, oxygen saturation (SatO₂), systolic blood pressure (SBP), and heart rate (HR) were evaluated.

Results

Groups were comparable (p=ns) with regard to cardiovascular risks factors. The incidence of side effects was similar across BMI (p=ns), although the TE patients showed improved profiles over those with SS exercise, with a significantly lower incidence of flushing, dizziness and nausea/gastrointestinal discomfort (12.9% vs. 28.4%; 19.9% vs. 33.4%; 11.4% vs. 19.2%, respectively; all p<0.05).

Regarding the hemodynamic response, we did not observe significant changes in SBP and HR after regadenoson administration across BMI categories. Comparing the TE and SS groups, no significant changes were observed in SBP, but there was a higher increase in HR in the TE group (p<0.05).

Conclusions

Regadenoson in combination with low-level exercise is safe and well tolerated over a wide range of BMI, with TE exercise showing a better side effect profile than SS.

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The conflict between treatment optimization and registration of radiopharmaceuticals with fixed activity posology in oncological nuclear medicine therapy

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Axillary blue sentinel lymph node: an unusual tattoo?

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Prognostic importance of lymph node-to-primary tumor standardized uptake value ratio in invasive squamous cell carcinoma of uterine cervix

Abstract

Purpose

Using integrated PET/CT, we evaluated the prognostic value of [¹⁸F]FDG uptake ratio between pelvic lymph node (LN) and primary tumor in invasive squamous cell carcinoma (SCCA) of the uterine cervix.

Methods

We retrospectively reviewed patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB to IIA cervical SCCA who underwent preoperative [¹⁸F]FDG PET/CT scans. PET/CT parameters such as maximum standardized uptake value (SUV) of the primary cervical cancer (SUV_cervix) and LN (SUV_LN), and the LN-to-cervical cancer SUV ratio (SUV_LN/SUV_cervix) were assessed. Prognostic values of PET/CT-derived metabolic and volumetric variables and clinicopathology parameters were analyzed to predict progression-free survival (PFS) in regression analyses.

Results

Clinical data, treatment modalities, and results were reviewed for 103 eligible patients. Median post-surgical follow-up was 29 months (range, 6–89), and 19 (18.5%) patients experienced recurrence. Multivariate logistic regression analysis showed that SUV_LN / SUV_cervix > 0.1747(P = 0.048) was the independent risk factor of recurrence. Patient group categorized by SUV_LN/SUV_cervix showed significant difference in PFS (log-rank test, P < 0.001).

Conclusions

Preoperative SUV_LN/SUV_cervix measured by [¹⁸F]FDG PET/CT was significantly associated with recurrence, and has an incremental prognostic value for PFS in patients with cervical SCCA.

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Metabolic volume performs better than SUVmax in the detection of left ventricular assist device driveline infection

Abstract

Purpose

A continuous-flow left ventricular assist device (LVAD) is a new and highly promising therapy in supporting end-stage heart failure patients, either bridging them to heart transplantation or as a destination therapy. Infection is one of the major complications associated with LVAD implants. ¹⁸F–FDG PET/CT has already been shown to be useful in the detection of LVAD infection. The goal of this study was to compare the diagnostic accuracy of different PET analysis techniques (visual grading versus SUVmax and metabolic volume).

Methods

We retrospectively analyzed 48 patients with implanted LVAD who underwent an ¹⁸F–FDG PET/CT that were either suspected to have a driveline or device infection or inflammation of unknown origin. PET/CT was analyzed qualitatively (visual grading) and quantitatively (SUVmax and metabolic volume) and matched to the final clinical diagnosis concerning driveline infection. The final diagnosis (standard of reference) was made at the end of clinically recorded follow-up or transplantation and included microbiological cultures of the driveline exit site and/or surgical samples, and clinical signs of infection despite negative cultures as well as recurrence of symptoms.

Results

Sensitivity, specificity, positive and negative predictive value were 87.5%, 79%, 81% and 86% for visual score, 87.5%, 87.5%, 87.5% and 87.5% for SUVmax and 96%, 87.5%, 88.5%, 95.5% for metabolic volume, respectively. ROC analysis revealed an AUC of .929 for SUVmax and .969 for metabolic volume. Both SUVmax and metabolic volume had a high detection rate of patients with driveline infection (21/24 = 91.5% true positive vs. 23/26 = 88.5% true positive, respectively). However, metabolic volume detected more patients without any infection correctly (1/22 = 4.5% false negative vs. 3/24 = 12.5% false negative).

Conclusions

¹⁸F–FDG PET/CT is a valuable tool for the diagnosis of LVAD driveline infection with high diagnostic accuracy. Particularly the use of the metabolic volume yields very high accuracy and performs slightly better than SUVmax.

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Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11 C-hydroxyephedrine PET study

Abstract

Purpose

This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by ¹¹C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF).

Methods

Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). ¹¹C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a ¹¹C-HED retention index (RI, %/min). To identify predictors of regional ¹¹C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix.

Results

Global ¹¹C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional ¹¹C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = −0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional ¹¹C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional ¹¹C-HED RI in HFpEF patients (both P ≤ 0.001).

Conclusion

Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.

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Integrated 18F–FDG PET/MRI compared to MRI alone for identification of local recurrences of soft tissue sarcomas: a comparison trial

Abstract

Purpose

To assess and compare the diagnostic accuracy of PET/MRI and MRI alone for the detection of local recurrences of soft tissue sarcomas (STS) after initial surgical resection of the primary tumors.

Material and methods

A total of 41 patients with clinically suspected tumor relapse of STS underwent an ¹⁸F–FDG-PET/MRI examination for assessment of local recurrence. Two experienced physicians interpreted the MRI data and subsequently the PET/MRI datasets in two separate reading sessions and were instructed to identify potential local tumor recurrences. Additionally, the diagnostic confidence in each reading for the identification of malignant lesions was determined. A McNemar test was applied to test for differences of both ratings and a Wilcoxon signed-rank test was used to identify differences of the confidence levels. Histopathological verification and follow-up imaging were applied for standard of reference.

Results

Tumor relapse was present in 27/41 patients. Calculated sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the detection of local tumor recurrence was 82%, 86%, 92%, 71% and 83% for MRI, and 96%, 79%, 90%, 92% and 90% for PET/MRI (p > 0.05). Furthermore, PET/MRI showed significantly higher confidence levels (p < 0.05) for the determination of malignant lesions.

Conclusion

Our results endorse ¹⁸F–FDG PET/MRI to be an excellent imaging method in the evaluation of recurrent STS after surgical excision, yielding superior tumor detection when compared to MRI alone.

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Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from 18 F-FDG PET/CT in operable triple-negative breast cancer

Abstract

Purpose

Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters.

Methods

A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters.

Results

All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage (P = 0.010), N stage (P < 0.001), and TNM stage (P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N (P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P < 0.001) were significant parameters.

Conclusions

Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by ¹⁸F-FDG PET/CT, rather than tumor parameters.

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Highlights of articles published in annals of nuclear medicine 2016

Abstract

This article is the first installment of highlights of selected articles published during 2016 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. A companion article highlighting selected articles published during 2016 in the European Journal of Nuclear Medicine and Molecular Imaging, which is the official peer-reviewed journal of the European Association of Nuclear Medicine, will also appear in the Annals Nuclear Medicine. This new initiative by the respective journals will continue as an annual endeavor and is anticipated to not only enhance the scientific collaboration between Europe and Japan but also facilitate global partnership in the field of nuclear medicine and molecular imaging.

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Role of interim 18 F-FDG-PET/CT for the early prediction of clinical outcomes of Non-Small Cell Lung Cancer (NSCLC) during radiotherapy or chemo-radiotherapy. A systematic review

Abstract

Background

Non-Small Cell Lung Cancer (NSCLC) is characterized by aggressiveness and includes the majority of thorax malignancies. The possibility of early stratification of patients as responsive and non-responsive to radiotherapy with a non-invasive method is extremely appealing. The distribution of the Fluorodeoxyglucose (¹⁸F–FDG) in tumours, provided by Positron-Emission-Tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT).

Objectives

In the last years, particular efforts have been focused on the possibility of using ad interim ¹⁸F–FDG PET (FDG_int) to evaluate response already in the course of radiotherapy. However, controversial findings have been reported for various malignancies, although several results would support the use of FDG_int for individual therapeutic decisions, at least in some pathologies. The objective of the present review is to assemble comprehensively the literature concerning NSCLC, to evaluate where and whether FDG_int may offer predictive potential.

Methods

Several searches were completed on Medline and the Embase database, combining different keywords. Original papers published in the English language from 2005 to 2016 with studies involving FDG_int in patients affected by NSCLC and treated with radiation therapy or chemo-radiotherapy only were chosen.

Results

Twenty-one studies out of 970 in Pubmed and 1256 in Embase were selected, reporting on 627 patients.

Conclusion

Certainly, the lack of univocal PET parameters was identified as a major drawback, while standardization would be required for best practice. In any case, all these papers denoted FDG_int as promising and a challenging examination for early assessment of outcomes during CRT, sustaining its predictivity in lung cancer.

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Role of ICG- 99m Tc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study

Abstract

Purpose

Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-^99mTc-nanocolloid in SLN detection in patients with cervical cancer.

Methods

This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19–21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry.

Results

Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved.

Conclusions

SLNB with ICG-^99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.

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The potential of 223 Ra and 18 F-fluoride imaging to predict bone lesion response to treatment with 223 Ra-dichloride in castration-resistant prostate cancer

Abstract

Purpose

The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of ²²³Ra-dichloride, to assess the relationship between those doses and corresponding ¹⁸F-fluoride uptake and to assess the potential of quantitative ¹⁸F-fluoride imaging to predict response to treatment.

Methods

Five patients received two intravenous injections of ²²³Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of ²²³Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial ²²³Ra scans. PET/CT imaging using ¹⁸F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline.

Results

Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5–11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in ¹⁸F-fluoride uptake was demonstrated (r² = 0.52). A log-linear relationship was demonstrated (r² = 0.77) between baseline measurements of ¹⁸F-fluoride uptake prior to ²²³Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both ²²³Ra and ¹⁸F-fluoride uptake in lesions (r = 0.75) as well as between ²²³Ra absorbed dose and ¹⁸F-fluoride uptake (r = 0.96).

Conclusions

There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between ²²³Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of ¹⁸F-fluoride in bone metastases is significantly correlated with corresponding uptake of ²²³Ra, the associated ²²³Ra absorbed dose and subsequent lesion response to treatment.

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Risk of cause-specific death in individuals with cancer – modifying role diabetes, statins, and metformin

Abstract

Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all-cause and cause-specific mortality dynamics in relation to baseline DM, statin use, and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow-up, and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage, and calendar period. Statin usage was associated with a reduced cancer-specific mortality with incidence rate ratio (IRR) 0.72 (95% confidence interval 0.69-0.74), IRR for CVD mortality was 0.95 (0.88-1.02), and for other causes 0.64 (0.56-0.74). In a sub-population of DM patients, IRR for metformin in all-cause mortality was 0.74 (0.71-0.78), in cancer mortality 0.75 (0.72-0.79), in CVD mortality 0.75 (0.68-0.83), and other causes 0.68 (0.60-0.78). In conclusion, our register-based study of survival after cancer diagnosis showed that patients with diabetes had substantially poorer outcome in all measures. An association between baseline statin usage and lower all-cause, cancer, and cardiovascular mortality was modified by cancer type. The effect of statin use was largest for breast and colorectal cancer. Metformin usage in a subpopulation of oral antidiabetic users was in general associated with lower mortality, but this association was modified by cancer type. The association was strongest for liver, colorectal, and breast cancer. This article is protected by copyright. All rights reserved.

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Temporomandibular joint reconstruction after condylar fracture complication related to osteosynthesis material

Publication date: Available online 24 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): J.F.C. Dantas, J.N. Nogueira Neto, V.A. Sarmento, P.S.F. Campos
Total condylar resorption and the failure of bone synthesis material as postoperative complications of condyle fracture are seldom reported in the literature. When these occur, they may severely limit temporomandibular joint (TMJ) function. In such cases, a reconstruction of the joint is indicated, which can be achieved by means of an alloplastic prosthesis. This article reports a rare case of impaction of osteosynthesis material in the region of the base of the skull associated with a mandibular condyle fracture treated with rigid internal fixation, which resulted in complications. There was progression to condylar resorption, requiring an alloplastic TMJ reconstruction, which was performed in a single surgical session.



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The impact of treatment for head and neck cancer on positive psychological change within a year of completing treatment

Publication date: Available online 24 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): S. Harding, T.P. Moss
Head and neck cancer carries a high level of morbidity and mortality. So why could anyone find having such a disease a positive event? The adversity hypothesis of "what doesn't kill you makes you stronger" suggests that people can use adversity to develop as human beings. This positive psychological change has received little attention in relation to head and neck cancer. Responses to the Silver Lining Questionnaire, University of Washington Quality of Life Questionnaire, and Short-Form 12 were collected from a postal survey, 3 to 12 months after the completion of treatment for head and neck cancer. Fifty-two (63%) people returned the survey and were included in the analysis. Time since completion of therapy did not show any relationship with positive psychological change. Tumour stage and treatment regimen both had a relationship with positive change. Participants with lower stage tumours had higher levels of positive change than those with tumours of higher stages. Participants who had surgery alone reported more positive change than those who had surgery with radiotherapy. A social factor related to greater change was being married or living with a partner when compared to living alone. Further research would aid the identification of bio-psychosocial factors that influence the development of positive psychological change and inform the development of rehabilitation interventions.



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AI software developed at @UWaterloo spots melanoma markers, speeding up diagnosishttps://t.co/MXrIcd4QNV https://t.co/gHqScgx1a0

AI software developed at @UWaterloo spots melanoma markers, speeding up diagnosis https://t.co/MXrIcd4QNV https://t.co/gHqScgx1a0

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Temporomandibular joint reconstruction after condylar fracture complication related to osteosynthesis material

Publication date: Available online 24 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): J.F.C. Dantas, J.N. Nogueira Neto, V.A. Sarmento, P.S.F. Campos
Total condylar resorption and the failure of bone synthesis material as postoperative complications of condyle fracture are seldom reported in the literature. When these occur, they may severely limit temporomandibular joint (TMJ) function. In such cases, a reconstruction of the joint is indicated, which can be achieved by means of an alloplastic prosthesis. This article reports a rare case of impaction of osteosynthesis material in the region of the base of the skull associated with a mandibular condyle fracture treated with rigid internal fixation, which resulted in complications. There was progression to condylar resorption, requiring an alloplastic TMJ reconstruction, which was performed in a single surgical session.



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The impact of treatment for head and neck cancer on positive psychological change within a year of completing treatment

Publication date: Available online 24 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): S. Harding, T.P. Moss
Head and neck cancer carries a high level of morbidity and mortality. So why could anyone find having such a disease a positive event? The adversity hypothesis of "what doesn't kill you makes you stronger" suggests that people can use adversity to develop as human beings. This positive psychological change has received little attention in relation to head and neck cancer. Responses to the Silver Lining Questionnaire, University of Washington Quality of Life Questionnaire, and Short-Form 12 were collected from a postal survey, 3 to 12 months after the completion of treatment for head and neck cancer. Fifty-two (63%) people returned the survey and were included in the analysis. Time since completion of therapy did not show any relationship with positive psychological change. Tumour stage and treatment regimen both had a relationship with positive change. Participants with lower stage tumours had higher levels of positive change than those with tumours of higher stages. Participants who had surgery alone reported more positive change than those who had surgery with radiotherapy. A social factor related to greater change was being married or living with a partner when compared to living alone. Further research would aid the identification of bio-psychosocial factors that influence the development of positive psychological change and inform the development of rehabilitation interventions.



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'Heartbreaking': Coast boy's leukemia battle in final days - The Sunshine Coast Daily

'Heartbreaking': Coast boy's leukemia battle in final days The Sunshine Coast Daily She said doctors were concerned with the rate at which the leukemia was returning to his bone marrow, and neurosurgeons have been trying to understand what is causing the swelling in the brain. Multiple tests for infections have all turned out negative ...

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Efficacy of Extended Adjuvant Therapy with Aromatase Inhibitors in Early Breast Cancer among Common Clinicopathologically-defined Subgroups: A Systematic Review and Meta-analysis

Publication date: Available online 24 August 2017
Source:Cancer Treatment Reviews
Author(s): Hadar Goldvaser, Ibrahim AlGorashi, Domen Ribnikar, Bostjan Seruga, Arnoud J. Templeton, Alberto Ocana, Eitan Amir
BackgroundRandomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5 years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically.MethodsWe identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age (<60 ±5 years versus ≥60 ±5 years), tumor size (>2cm versus ≤2cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no).ResultsSeven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference=0.44), nodal involvement (HR=0.72 versus 0.83, p for difference=0.22), double hormone receptor expression (HR=0.68 versus 1.01, p for difference=0.31) and receipt of adjuvant chemotherapy (HR=0.71 versus 0.80, p for difference=0.51).ConclusionsExtended treatment with AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The combination of greater effect size and higher absolute risk of recurrence in node positive and larger tumors will likely translate to higher absolute benefits from extended AIs in these groups.



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Determination of glucose-6-phosphate dehydrogenase cut-off values in a Tunisian population

Authors: Laouini, Naouel / Sahli, Chaima Abdelhafidh / Jouini, Latifa / Haloui, Sabrine / Fredj, Sondes Hadj / Daboubi, Rym / Siala, Hajer / Ouali, Faida / Becher, Meriam / Toumi, Nourelhouda / Bibi, Amina / Messsaoud, Taieb


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Spelunking for lipids in caveolae [Cell Biology]

Phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) have been implicated in the maintenance of caveolae, but direct evidence that these lipids are required for normal caveolar structure and dynamics in living cells has been lacking. A new study by Fairn and colleagues uses sophisticated tools to perturb specific lipids in living cells to assess the consequences for caveolae. This study demonstrates disparate roles for these lipids in the stability and mobility of caveolae and points the way for future work to understand how these lipids contribute to the biology of caveolae.

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Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane [Cell Biology]

Caveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns(4,5)P2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.

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Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding. [Additions and Corrections]

VOLUME 285 (2010) PAGES 17525–17536Fig. 5E and supplemental Fig. S3A contained inadvertent image duplications. These errors have been corrected and do not affect the results or conclusions of this work.jbc;292/34/14310/FU1F1FU1

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Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex [Membrane Biology]

The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex.

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Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells. [Withdrawals/Retractions]

VOLUME 283 (2008) PAGES 13736–13744This article has been withdrawn by the authors because of errors that occurred in the construction of Figs. 1D, 3C, 5C, and 5H, and supplemental Fig. 1A have been brought to their attention. The authors state that the errors do not affect the conclusions of the article, which have been confirmed in subsequent articles.

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Shining a light on GPCR complexes [Membrane Biology]

The G protein–coupled receptor (GPCR) signaling pathways mediating information exchange across the cell membrane are central to a variety of biological processes and therapeutic strategies, but visualizing the molecular-level details of this exchange has been difficult for all but a few GPCR–G protein complexes. A study by Gao et al. now reports new strategies and tools to obtain receptor complexes in a near-native state, revealing insights into the gross conformational features of rhodopsin-transducin interactions and setting the stage for future studies.

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Proton transfer reactions in the red light-activatable channelrhodopsin variant ReaChR and their relevance for its function [Protein Structure and Folding]

Channelrhodopsins (ChRs) are light-gated ion channels widely used for activating selected cells in large cellular networks. ChR variants with a red-shifted absorption maximum, such as the modified Volvox carteri ChR1 red-activatable channelrhodopsin ("ReaChR," λmax = 527 nm), are of particular interest because longer wavelengths allow optical excitation of cells in deeper layers of organic tissue. In all ChRs investigated so far, proton transfer reactions and hydrogen bond changes are crucial for the formation of the ion-conducting pore and the selectivity for protons versus cations, such as Na+, K+, and Ca2+ (1). By using a combination of electrophysiological measurements and UV-visible and FTIR spectroscopy, we characterized the proton transfer events in the photocycle of ReaChR and describe their relevance for its function. 1) The central gate residue Glu130 (Glu90 in Chlamydomonas reinhardtii (Cr) ChR2) (i) undergoes a hydrogen bond change in D → K transition and (ii) deprotonates in K → M transition. Its negative charge in the open state is decisive for proton selectivity. 2) The counter-ion Asp293 (Asp253 in CrChR2) receives the retinal Schiff base proton during M-state formation. Starting from M, a photocycle branching occurs involving (i) a direct M → D transition and (ii) formation of late photointermediates N and O. 3) The DC pair residue Asp196 (Asp156 in CrChR2) deprotonates in N → O transition. Interestingly, the D196N mutation increases 15-syn-retinal at the expense of 15-anti, which is the predominant isomer in the wild type, and abolishes the peak current in electrophysiological measurements. This suggests that the peak current is formed by 15-anti species, whereas 15-syn species contribute only to the stationary current.

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A CRISPR/Cas9 approach reveals that the polymerase activity of DNA polymerase {beta} is dispensable for HIV-1 infection in dividing and nondividing cells [DNA and Chromosomes]

Retrovirus integration into the host genome relies on several host enzymes, potentially including DNA polymerase β (Pol β). However, whether human Pol β is essential for lentivirus replication in human cells is unclear. Here, we abolished DNA polymerase β (Pol β) expression by targeting its DNA polymerase domain with CRISPR/Cas9 in human monocytic THP-1 cells to investigate the role of Pol β in HIV-1 transduction in both dividing and nondividing macrophage stages of THP-1 cells. Pol β–knock-out was confirmed by enhanced sensitivity to methyl methanesulfonate-induced DNA damage. Of note, nuclear extracts from Pol β–knock-out THP-1 cells prepared from both dividing and nondividing stages displayed significantly reduced capability to repair the gapped HIV-1 integration intermediate DNA substrate in a biochemical simulation. However, nuclear extract from both dividing and nondividing stages of the Pol β–KO cells had detectable gap repair activity, suggesting that other host DNA polymerases also repair gapped HIV-1 DNA, particularly in dividing cells. Next, when we compared transduction using HIV-1 and simian immunodeficiency virus in control and Pol β–KO cells, the loss of the Pol β expression did not affect transduction efficiency of these lentiviruses in both dividing and nondividing stages. Finally, the gap repair assay indicated that limited cellular dNTP pools, but not Pol β expression, are a primary factor for HIV-1 DNA gap repair, particularly in nondividing cells. These data support the idea that Pol β polymerase activity is dispensable for HIV-1 infection in both dividing and nondividing stages of human cells targeted by the virus.

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Structural and biochemical analyses indicate that a bacterial persulfide dioxygenase-rhodanese fusion protein functions in sulfur assimilation [Enzymology]

Hydrogen sulfide (H2S) is a signaling molecule that is toxic at elevated concentrations. In eukaryotes, it is cleared via a mitochondrial sulfide oxidation pathway, which comprises sulfide quinone oxidoreductase, persulfide dioxygenase (PDO), rhodanese, and sulfite oxidase and converts H2S to thiosulfate and sulfate. Natural fusions between the non-heme iron containing PDO and rhodanese, a thiol sulfurtransferase, exist in some bacteria. However, little is known about the role of the PDO–rhodanese fusion (PRF) proteins in sulfur metabolism. Herein, we report the kinetic properties and the crystal structure of a PRF from the Gram-negative endophytic bacterium Burkholderia phytofirmans. The crystal structures of wild-type PRF and a sulfurtransferase-inactivated C314S mutant with and without glutathione were determined at 1.8, 2.4, and 2.7 Å resolution, respectively. We found that the two active sites are distant and do not show evidence of direct communication. The B. phytofirmans PRF exhibited robust PDO activity and preferentially catalyzed sulfur transfer in the direction of thiosulfate to sulfite and glutathione persulfide; sulfur transfer in the reverse direction was detectable only under limited turnover conditions. Together with the kinetic data, our bioinformatics analysis reveals that B. phytofirmans PRF is poised to metabolize thiosulfate to sulfite in a sulfur assimilation pathway rather than in sulfide stress response as seen, for example, with the Staphylococcus aureus PRF or sulfide oxidation and disposal as observed with the homologous mammalian proteins.

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Equilibrium and ultrafast kinetic studies manipulating electron transfer: A short-lived flavin semiquinone is not sufficient for electron bifurcation [Enzymology]

Flavin-based electron transfer bifurcation is emerging as a fundamental and powerful mechanism for conservation and deployment of electrochemical energy in enzymatic systems. In this process, a pair of electrons is acquired at intermediate reduction potential (i.e. intermediate reducing power), and each electron is passed to a different acceptor, one with lower and the other with higher reducing power, leading to "bifurcation." It is believed that a strongly reducing semiquinone species is essential for this process, and it is expected that this species should be kinetically short-lived. We now demonstrate that the presence of a short-lived anionic flavin semiquinone (ASQ) is not sufficient to infer the existence of bifurcating activity, although such a species may be necessary for the process. We have used transient absorption spectroscopy to compare the rates and mechanisms of decay of ASQ generated photochemically in bifurcating NADH-dependent ferredoxin-NADP+ oxidoreductase and the non-bifurcating flavoproteins nitroreductase, NADH oxidase, and flavodoxin. We found that different mechanisms dominate ASQ decay in the different protein environments, producing lifetimes ranging over 2 orders of magnitude. Capacity for electron transfer among redox cofactors versus charge recombination with nearby donors can explain the range of ASQ lifetimes that we observe. Our results support a model wherein efficient electron propagation can explain the short lifetime of the ASQ of bifurcating NADH-dependent ferredoxin-NADP+ oxidoreductase I and can be an indication of capacity for electron bifurcation.

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Short-term starvation is a strategy to unravel the cellular capacity of oxidizing specific exogenous/endogenous substrates in mitochondria [Metabolism]

Mitochondrial oxidation of nutrients is tightly regulated in response to the cellular environment and changes in energy demands. In vitro studies evaluating the mitochondrial capacity of oxidizing different substrates are important for understanding metabolic shifts in physiological adaptations and pathological conditions, but may be influenced by the nutrients present in the culture medium or by the utilization of endogenous stores. One such influence is exemplified by the Crabtree effect (the glucose-mediated inhibition of mitochondrial respiration) as most in vitro experiments are performed in glucose-containing media. Here, using high-resolution respirometry, we evaluated the oxidation of endogenous or exogenous substrates by cell lines harboring different metabolic profiles. We found that a 1-h deprivation of the main energetic nutrients is an appropriate strategy to abolish interference of endogenous or undesirable exogenous substrates with the cellular capacity of oxidizing specific substrates, namely glutamine, pyruvate, glucose, or palmitate, in mitochondria. This approach primed mitochondria to immediately increase their oxygen consumption after the addition of the exogenous nutrients. All starved cells could oxidize exogenous glutamine, whereas the capacity for oxidizing palmitate was limited to human hepatocarcinoma Huh7 cells and to C2C12 mouse myoblasts that differentiated into myotubes. In the presence of exogenous glucose, starvation decreased the Crabtree effect in Huh7 and C2C12 cells and abrogated it in mouse neuroblastoma N2A cells. Interestingly, the fact that the Crabtree effect was observed only for mitochondrial basal respiration but not for the maximum respiratory capacity suggests it is not caused by a direct effect on the electron transport system.

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Function of inhibitor of Bruton's tyrosine kinase isoform {alpha} (IBTK{alpha}) in nonalcoholic steatohepatitis links autophagy and the unfolded protein response [Signal Transduction]

Nonalcoholic fatty liver disease (steatosis) is the most prevalent liver disease in the Western world. One of the advanced pathologies is nonalcoholic steatohepatitis (NASH), which is associated with induction of the unfolded protein response (UPR) and disruption of autophagic flux. However, the mechanisms by which these processes contribute to the pathogenesis of human diseases are unclear. Herein, we identify the α isoform of the inhibitor of Bruton's tyrosine kinase (IBTKα) as a member of the UPR, whose expression is preferentially translated during endoplasmic reticulum (ER) stress. We found that IBTKα is located in the ER and associates with proteins LC3b, SEC16A, and SEC31A and plays a previously unrecognized role in phagophore initiation from ER exit sites. Depletion of IBTKα helps prevent accumulation of autophagosome intermediates stemming from exposure to saturated free fatty acids and rescues hepatocytes from death. Of note, induction of IBTKα and the UPR, along with inhibition of autophagic flux, was associated with progression from steatosis to NASH in liver biopsies. These results indicate a function for IBTKα in NASH that links autophagy with activation of the UPR.

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The role of the Met20 loop in the hydride transfer in Escherichia coli dihydrofolate reductase [Computational Biology]

A key question concerning the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) is whether the Met20 loop is dynamically coupled to the chemical step during catalysis. A more basic, yet unanswered question is whether the Met20 loop adopts a closed conformation during the chemical hydride transfer step. To examine the most likely conformation of the Met20 loop during the chemical step, we studied the hydride transfer in wild type (WT) ecDHFR using hybrid quantum mechanics-molecular mechanics free energy simulations with the Met20 loop in a closed and disordered conformation. Additionally, we investigated three mutant forms (I14X; X = Val, Ala, Gly) of the enzyme that have increased active site flexibility and donor-acceptor distance dynamics in closed and disordered Met20 loop states. We found that the conformation of the Met20 loop has a dramatic effect on the ordering of active site hydration, although the Met20 loop conformation only has a moderate effect on the hydride transfer rate and donor-acceptor distance dynamics. Finally, we evaluated the pKa of the substrate N5 position in closed and disordered Met20 loop states and found a strong correlation between N5 basicity and the conformation of the Met20 loop.

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Demethylation of induced pluripotent stem cells from type 1 diabetic patients enhances differentiation into functional pancreatic {beta} cells [Developmental Biology]

Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield. The cells responded to high-glucose stimulation by secreting insulin in vitro. The shape, size, and number of their granules, as observed by transmission electron microscopy, were identical to those found in cadaveric β cells. When the IPCs were transplanted into immunodeficient mice that had developed streptozotocin-induced diabetes, they promoted a dramatic decrease in hyperglycemia, causing the mice to become normoglycemic within 28 days. None of the mice died or developed teratomas. Because the cells are derived from "self," immunosuppression is not required, providing a much safer and reliable treatment option for T1D patients. Moreover, these cells can be used for drug screening, thereby accelerating drug discovery. In conclusion, our approach eliminates the need for cadaveric pancreatic tissue.

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The long non-coding RNA GAS5 regulates transforming growth factor {beta} (TGF-{beta})-induced smooth muscle cell differentiation via RNA Smad-binding elements [Signal Transduction]

Smooth muscle cell (SMC) differentiation is essential for vascular development, and TGF-β signaling plays a critical role in this process. Although long non-coding RNAs (lncRNAs) regulate various cellular events, their functions in SMC differentiation remain largely unknown. Here, we demonstrate that the lncRNA growth arrest-specific 5 (GAS5) suppresses TGF-β/Smad3 signaling in smooth muscle cell differentiation of mesenchymal progenitor cells. We found that forced expression of GAS5 blocked, but knockdown of GAS5 increased, the expression of SMC contractile proteins. Mechanistically, GAS5 competitively bound Smad3 protein via multiple RNA Smad–binding elements (rSBEs), which prevented Smad3 from binding to SBE DNA in TGF-β–responsive SMC gene promoters, resulting in suppression of SMC marker gene transcription and, consequently, in inhibition of TGF-β/Smad3-mediated SMC differentiation. Importantly, other lncRNAs or artificially synthesized RNA molecules that contained rSBEs also effectively inhibited TGF-β/Smad3 signaling, suggesting that lncRNA–rSBE may be a general mechanism used by cells to fine-tune Smad3 activity in both basal and TGF-β–stimulated states. Taken together, our results have uncovered an lncRNA-based mechanism that modulates TGF-β/Smad3 signaling during SMC differentiation.

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p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation [Signal Transduction]

Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)–induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1–NFATc1–cyclin D1–CDK6–PKN1–CDK4–PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1–cyclin D1/CDK6 and upstream of CDK4–PAK1 in the p115 RhoGEF–Rac1–NFATc1–cyclin D1–CDK6–PKN1–CDK4–PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2–Gi/o–Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1–NFATc1–cyclin D1–CDK6–PKN1–CDK4–PAK1 signaling.

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Roadmap for investigating epigenome deregulation and environmental origins of cancer

The interaction between the (epi)genetic makeup of an individual and their environmental exposure record is accepted as a determinant factor for most human cancers. In an opinion paper published in the International Journal of Cancer, scientists from the Epigenetics Group at the International Agency for Research on Cancer (IARC) and partners review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. The article also discusses critical knowledge gaps and research needs and provides guidelines (a roadmap) for investigating epigenetic deregulation and environmental origins of cancer.
Herceg Z, Ghantous A, Wild CP, Sklias A, Casati L, Duthie SJ, et al.
Roadmap for investigating epigenome deregulation and environmental origins of cancer
Int J Cancer. Accepted manuscript online 24 August 2017; http://ift.tt/2vuVhds


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Conference Calendar

J Vasc Res 2017;54:257

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Membership of the ESM

J Vasc Res 2017;54:258

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A postal worker faked cancer and got paid to miss 2 years of work. Here's how a judge punished her. - Chicago Tribune

Chicago Tribune

A postal worker faked cancer and got paid to miss 2 years of work. Here's how a judge punished her. Chicago Tribune Caroline Boyle, who was convicted of fraud Tuesday in Colorado, worked for the USPS since 1991, and was planning to use sick leave until her retirement in April, which she planned to celebrate with a Hawaiian cruise, according to officials and court ... and more »

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Cancer of the Middle and Inner Ear - News-Medical.net

Cancer of the Middle and Inner Ear News-Medical.net Squamous cell carcinoma (SCC): Temporal bone cancer occurs in one of 5000–20,000 cases. Annually, it accounts for an incidence level of about 1–6 cases out of 1 million. Individuals may be diagnosed with temporal bone SCC when they are 50 or 60 ...

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Wound healing effect of Euphorbia hirta linn. (Euphorbiaceae) in alloxan induced diabetic rats

Euphorbia hirta linn., is a species of Euphorbiaceae family. They are known as asthma plant, barokhervi. The plant E. hirta is famous for its medicinal importance among the tribal popu...

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Survey finds lag in HPV vaccination rates for childhood cancer survivors - News-Medical.net

Newburgh Gazette

Survey finds lag in HPV vaccination rates for childhood cancer survivors News-Medical.net Persistent infection with certain high-risk strains of HPV can cause cancer of the cervix, vagina, penis, tongue, throat, anus and other sites. Previous studies from St. Jude and others found that childhood cancer survivors are at an increased risk of ... Most US teens getting HPV vaccine, CDC saysHiTechFacts all 19 news articles »

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Copyright Transfer Agreement

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Check List

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