Examining the efficacy of a multicomponent m-Health physical activity, diet and sleep intervention for weight loss in overweight and obese adults: randomised controlled trial protocol

Introduction

Traditional behavioural weight loss trials targeting improvements in physical activity and diet are modestly effective. It has been suggested that sleep may have a role in weight loss and maintenance. Improving sleep health in combination with physical activity and dietary behaviours may be one strategy to enhance traditional behavioural weight loss trials. Yet the efficacy of a weight loss intervention concurrently targeting improvements in physical activity, dietary and sleep behaviours remains to be tested.

Methods and analysis

The primary aim of this three-arm randomised controlled trial is to examine the efficacy of a multicomponent m-Health behaviour change weight loss intervention relative to a waitlist control group. The secondary aims are to compare the relative efficacy of a physical activity, dietary behaviour and sleep intervention (enhanced intervention), compared with a physical activity and dietary behaviour only intervention (traditional intervention), on the primary outcome of weight loss and secondary outcomes of waist circumference, glycated haemoglobin, physical activity, diet quality and intake, sleep health, eating behaviours, depression, anxiety and stress and quality of life. Assessments will be conducted at baseline, 6 months (primary endpoint) and 12 months (follow-up). The multicomponent m-Health intervention will be delivered using a smartphone/tablet 'app', supplemented with email and SMS and individualised in-person dietary counselling. Participants will receive a Fitbit, body weight scales to facilitate self-monitoring, and use the app to access educational material, set goals, self-monitor and receive feedback about behaviours. Generalised linear models using an analysis of covariance (baseline adjusted) approach will be used to identify between-group differences in primary and secondary outcomes, following an intention-to-treat principle.

Ethics and dissemination

The Human Research Ethics Committee of The University of Newcastle Australia provided approval: H-2017–0039. Findings will be disseminated via publication in peer-reviewed journals, conference presentations, community presentations and student theses.

Trial registration number

ACTRN12617000735358; UTN1111-1219-2050.

https://ift.tt/2CRH0Pa

TADAFER II: Tadalafil treatment for fetal growth restriction - a study protocol for a multicenter randomised controlled phase II trial

Introduction

There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR.

Methods and analysis

This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age.

Ethics and dissemination

This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications.

Trial registration number

UMIN000023778.

https://ift.tt/2P3onzl

Another look at what teachers and students think about interprofessional learning as a shared experience in Iran: a qualitative research

Objectives

To explore experiences of interprofessional learning (IPL), and how faculty and students might want to participate in IPL opportunities as a form of shared learning.

Design

Qualitative study.

Setting

The Ministry of Health and Medical Education which is accountable for rendering service to the public, providing healthcare needs and improving the quality of medical education was established in Iran in 1985, to integrate medical education with healthcare services.

Participants

A sample of six faculty members and seven students, purposively sampled for demographic characteristics and their experience regarding shared learning.

Methods

A descriptive qualitative study using thematic analysis of content was conducted. Data were obtained using semistructured interviews and then analysed thematically. Data collection and analysis were concurrent.

Results

Three categories were identified: the role of prologues in IPL, the role of structured IPL, and the role of context and structure in such a system for learning, representing seven subcategories.

Conclusion

The findings indicate that experiences of learning with different professionals are complex, and these experiences shape their present and future workplace relations. Matching the existing educational context and structure with IPL and providing planned interaction and reflection among professionals are necessary to support IPL.

https://ift.tt/2CTDHHz

Ecological study on the use of hormonal contraception, abortions and births among teenagers in the Nordic countries

Objectives

Compare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries.

Design

Ecological study using national registry data concerning births and abortions among all women aged 15–19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008–2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008–2015 were obtained from national databases in Denmark, Norway and Sweden.

Setting

Denmark, Finland, Iceland, Norway and Sweden.

Participants

Women 15–19 years old in all Nordic countries (749 709) and 13–19 years old in Denmark, Norway and Sweden (815 044).

Results

Both annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15–19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18–19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden.

Conclusions

Birth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers.

https://ift.tt/2OXUwbs

Clinicopathological Significance of the ET Axis in Human Oral Squamous Cell Carcinoma

Abstract

The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ET_AR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cell malignancy and the expressions of ET-1 and ET_AR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ET_AR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.

https://ift.tt/2Sraysx

Reply: TDP-43 mutations increase HNRNP A1-7B through gain of splicing function

Sir,

https://ift.tt/2SxGAmz

One hundred years ago: Nijinsky and the origins of schizophrenia

A footpath in the Square de la Tour Saint-Jacques in Paris is named for the dancer Vaslav Nijinsky (1889–1950). It was in the nearby Théâtre du Châtelet that the 'God of Dance' astounded audiences and scandalized critics with his pioneering choreography. However, it would not last—in March 1919, Nijinsky was diagnosed with schizophrenia, and the world lost the art of its greatest dancer. His case captured the interest of clinicians and the general public during the first half of the 20th century. An acquaintance with royalty, politicians and leading artists, he became a case for some of the most renowned psychiatrists of the day, including Bleuler, Binswanger, Wagner-Jauregg, Jung, Adler and Sakel. However, this is not merely a case of historical interest. Schizophrenia is a neurodevelopmental disorder in which premorbid motor and intellectual abnormalities are present before the onset of psychosis, which generally occurs in late adolescence; but Nijinsky was aged 30 at the time of his diagnosis and had arguably the most finely tuned motor skills in history. Here, his case is revisited, and discussed through the prism of novel pathophysiological mechanisms.

https://ift.tt/2zhfozO

Cognitive control involves theta power within trials and beta power across trials in the prefrontal-subthalamic network

Abstract

There is increasing evidence that the medial prefrontal cortex participates in conflict and feedback monitoring while the subthalamic nucleus adjusts actions. Yet how these two structures coordinate their activity during cognitive control remains poorly understood. We recorded from the human prefrontal cortex and the subthalamic nucleus simultaneously while participants (n = 22) performed a novel task involving high conflict trials, complete response inhibition trials, and trial-to-trial behavioural adaptations to conflict and errors. Overall, we found that within-trial adaptions to both conflict and complete response inhibition involved changes in the theta band while across-trial behavioural adaptations to both conflict and errors involved changes in the beta band (P < 0.05). Yet the role each region's theta and beta oscillations played during the task differed significantly between the two sites. Trials that involved either within-trial conflict or complete response inhibition were associated with increased theta phase synchrony between the medial prefrontal cortex and the subthalamic nucleus (P < 0.05). Despite increased synchrony, however, increases in prefrontal theta power were associated with response inhibition, while increases in subthalamic theta power were associated with response execution (P < 0.05). In the beta band, post-response increases in prefrontal beta power were suppressed when the completed trial contained either conflict or an erroneous response (P < 0.05). Subthalamic beta power, on the other hand, was only modified during the subsequent trial that followed a conflict or error trial. Notably, these adaptation trials exhibited slower response times (P < 0.05), suggesting that both brain regions contribute to across-trial adaptations but do so at different stages of the adaptation process. Taken together, our data shed light on the mechanisms underlying within-trial and across-trial cognitive control and how disruption of this network can negatively impact cognition. More broadly, however, our data also demonstrate that the specific role of a brain region, rather than the frequency being utilized, governs the behavioural correlates of oscillatory activity.

https://ift.tt/2SxYnds

TDP-43 mutations increase HNRNP A1-7B through gain of splicing function

Sir,

https://ift.tt/2zdT9L2

A Systematic Review in Support of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care, Fourth Edition

Palliative care continues to be a rapidly growing field aimed at improving quality of life for patients and their caregivers.

https://ift.tt/2SvCQlv

Ileal schwannoma causing intussusception in an adult

Ileal schwannomas are extremely rare tumours. Very few cases have been previously reported. Most cases present with abdominal pain and gastrointestinal bleeding; intussusception is a rare presentation. Due to limitations in imaging modalities, arriving at a diagnosis preoperatively can be challenging. The only reliable method of diagnosis, and treatment, is resection of the tumour, followed by histological and immunohistochemical testing. This report details the rare case of intussusception as the presenting feature of an ileal schwannoma.

https://ift.tt/2OlQ7tS

Infected and obstructed kidney secondary to sloughed necrotic renal papilla

Description  

A 66-year-old Afro-Caribbean woman presented with a 1-day history of sharp left flank pain. This was associated with nausea and diarrhoea, without fever or urinary symptoms. Her medical history includes type 2 diabetes mellitus on insulin therapy but with suboptimal control (haemoglobin A1c 80 mmol/mol or 0.23 g/dL glucose levels) and related complications including chronic kidney disease, retinopathy, peripheral neuropathy, hypertension, sickle cell trait, obesity and osteoarthritis. Blood investigations demonstrated leucocytosis (white cell count 12.7x10⁹/L) and deranged renal function (creatinine 150 µmol/L; baseline 110 µmol/L). Urine dipstick test was positive for nitrites, ketones and glucose and urine culture isolated mixed growth of bacteria with Candida.

A CT abdomen/pelvis, initially planned on the working diagnosis of acute diverticulitis, revealed a mild left-sided hydroureteronephrosis associated with perinephric inflammatory stranding. Left posterolateral bladder wall thickening and left distal ureteric enhancement were also highlighted (figures 1 and 2). The patient was...

https://ift.tt/2yI2prf

Salmonella Enteritidis breast abscess: an unusual cause of breast abscess in the UK

Breast abscess is a common clinical condition mostly caused by Staphylococcus aureus. However, infections due to mixed organisms are observed in non-lactational women, mostly in smokers. Salmonella infection causing breast abscess is extremely rare in developed countries. We report a case of Salmonella enterica subsp enterica (I) serovar Enteritidis breast abscess in a 48-year-old woman, a UK citizen, who had recently travelled abroad. She was treated successfully with a combination of surgery and ciprofloxacin. Unusual causative organisms should be kept in mind in patients with recent travel abroad and pus should be sent for microbiology. Mastitis caused by Salmonella spp can present with a severely indurated area that may take a few weeks to resolve. Complete assessment with biopsy of the indurated area and breast imaging is mandatory to exclude malignancy.

https://ift.tt/2OlQ1m0

Linezolid-associated serotonin toxicity after escitalopram discontinuation: concomitant drug considerations

We report a case of a hospitalised patient who developed probable serotonin toxicity shortly after the initiation of linezolid in whom the selective serotonin reuptake inhibitor (SSRI) escitalopram had been recently discontinued. On day 2 of linezolid administration, the patient reported severe anxiety and was observed to have full body jerking and twitching motions without mental status change. Notably, the patient was concomitantly receiving the antidepressant, trazodone and the benzodiazepine, clonazepam possibly affecting the severity and manifestations of serotonin toxicity. Linezolid was discontinued after 5 days and the patient's symptoms resolved. Serotonin toxicity can present with an array of symptoms and be life threatening if left unrecognised. This report highlights the clinical lessons that discontinuation of an SSRI upon initiation of linezolid does not eliminate the risk of serotonin toxicity and that other concomitant medications may worsen or improve some of the symptoms lending delay and uncertainty to the diagnosis.

https://ift.tt/2yHYBWX

Neurocysticercosis: a reversible and rare cause of seizure in the developed world

Description 

A 22-year-old man, originally from India, presented to an emergency department in Canada with a new-onset seizure and collapse associated with a few seconds of right eye and tongue deviation. This event occurred following 6 weeks of difficulty concentrating and unilateral left-sided headache. On examination, no focal neurological deficits were found. A non-contrast CT head was requested which showed a left-sided occipital lesion. A follow-up brain MRI revealed the 'hole-with-dot' lesion pathognomonic for neurocysticercosis (NCC).

NCC is caused by the tapeworm Taenia solium and is the most common parasitic infection of the central nervous system, endemic to many low-income countries worldwide. T. solium is transmitted among humans via the faecal–oral route, with pigs acting as an intermediate host. Humans are a definitive host for the intestinal tapeworm which produces eggs containing an infective embryo (oncosphere). This embryo can actively cross the intestinal wall into the blood stream and deposit in...

https://ift.tt/2Oguqes

Adjacent schwannomas originating from intercostal and sympathetic nerves

Description 

Schwannomas are the most frequent type of intrathoracic neurogenic tumour, but the presence of multiple simultaneous schwannomas is a rare occurrence. We experienced a patient initially thought to have a single schwannoma based on preoperative imaging, but who was subsequently found to have two adjacent schwannomas arising from different nerves.

A 48-year-old woman showed an abnormal shadow on chest X-ray during a medical examination. CT-guided biopsy did not provide a definitive diagnosis, and she was therefore referred to our department. Her general condition was good and her neurological findings were normal. No skin pigmentation or subcutaneous nodules were observed. Chest CT revealed a 5.5 cm segmental lobular tumour in the right posterior mediastinum (figure 1A) and chest MRI showed that the tumour continued from the right intervertebral foramina (figure 1B). We suspected schwannoma of the intercostal nerve, and performed video-assisted thoracoscopic surgery in the...

https://ift.tt/2yK7dMP

Prevalence and risk factors of deep venous thrombosis in patients with longitudinally extensive transverse myelitis: one center data from China

Deep venous thrombosis (DVT) is a severe complication in longitudinally extensive transverse myelitis (LETM) patients. It may interfere with LETM treatment and delay the recovery of the spinal dysfunction. How...

https://ift.tt/2qmTQO9

The Diesel Exhaust in Miners Study provides no evidence for an increase in risk for lung cancer in miners exposed to diesel engine emissions

Abstract

The Diesel Exhaust in Miners Study is unquestionably the most suitable data material to date to examine a possible link between diesel engine emissions and lung cancer risk. But the results do not appear to be consistent in themselves. The crucial methodological problem in this study, however, has yet to be discovered, to which the lack of any description of age related information (year of birth, year of hire, year of first exposure, year of death) for the cohort as well as for the cases might have contributed. This information is important to understand the flaws in the analysis. It turns out that the year of birth is associated with the exposure, i.e. with the chance to be exposed over a certain period of time as well as with the chance to be an ever-smoker. A further important issue for the interpretation of the results is the validity of the data on smoking, which are mainly obtained from next of kin for decedents up to 50 years after death. Taking all these aspects into account, it can be concluded that only the SMR-analysis can be considered from all published results.

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Occurrence of Acute Mountain Sickness in Nonclimbing Tourists at Mount Mitchell, North Carolina (2037 m)

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2PzJ8C0

Cancers, Vol. 10, Pages 413: Mechanisms of Lysophosphatidic Acid-Mediated Lymphangiogenesis in Prostate Cancer

Cancers, Vol. 10, Pages 413: Mechanisms of Lysophosphatidic Acid-Mediated Lymphangiogenesis in Prostate Cancer

Cancers doi: 10.3390/cancers10110413

Authors: Pei-Yi Wu Yueh-Chien Lin Yuan-Li Huang Wei-Min Chen Chien-Chin Chen Hsinyu Lee

Prostate cancer (PCa) is the most common noncutaneous cancer in men worldwide. One of its major treatments is androgen deprivation therapy, but PCa frequently relapses as aggressive castration resistant local tumors and distal metastases. Hence, the development of novel agents or treatment modalities for advanced PCa is crucial. Many tumors, including PCa, first metastasize to regional lymph nodes via lymphatic vessels. Recent findings demonstrate that the bioactive lipid lysophosphatidic acid (LPA) promotes PCa progression by regulating vascular endothelial growth factor-C (VEGF-C), a critical mediator of tumor lymphangiogenesis and lymphatic metastasis. Many of the underlying molecular mechanisms of the LPA&ndash;VEGF-C axis have been described, revealing potential biomarkers and therapeutic targets that may aid in the diagnosis and treatment of advanced PCa. Herein, we review the literature that illustrates a functional role for LPA signaling in PCa progression. These discoveries may be especially applicable to anti-lymphangiogenic strategies for the prevention and therapy of metastatic PCa.

https://ift.tt/2Q6XAhT

Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer

Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer

Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer, Published online: 31 October 2018; doi:10.1038/s41416-018-0198-3

Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer

https://ift.tt/2PDO88Z

Immune dysregulation in cancer patients developing immune-related adverse events

Immune dysregulation in cancer patients developing immune-related adverse events

Immune dysregulation in cancer patients developing immune-related adverse events, Published online: 31 October 2018; doi:10.1038/s41416-018-0155-1

Immune dysregulation in cancer patients developing immune-related adverse events

https://ift.tt/2PyGD2O

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer, Published online: 31 October 2018; doi:10.1038/s41416-018-0298-0

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer

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Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer

Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer

Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer, Published online: 31 October 2018; doi:10.1038/s41416-018-0262-z

Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer

https://ift.tt/2Pw9qoR

Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma

Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma

Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma, Published online: 31 October 2018; doi:10.1038/s41416-018-0199-2

Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma

https://ift.tt/2RqqgCO

Upregulation of Circular RNA VPS13C-has-circ-001567 Promotes Ovarian Cancer Cell Proliferation and Invasion

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Integrative Analysis of Transcriptomic and Methylomic Data in Photoperiod-Dependent Regulation of Cucumber Sex Expression

The cucumber (Cucumis sativus) is characterized by its diversity and seasonal plasticity in sexual type. A long day length condition significantly decreased the cucumber female flower ratio by 17.7%-52.9%, and the effect of photoperiod treatment is more significant under low temperature than under high temperature. Transcriptome analysis indicates that the photoperiod treatment preferentially significantly influenced flower development processes, particularly MADS-box genes in shoot apices. The long-day treatment resulted in predominantly transposable element (TE)- and gene-associated CHH-types of DNA methylation changes. Nevertheless, there was significant enrichment of CG- and CHG-types of DNA methylation changes nearing transcription start sites (TSSs)/transcription end sites (TESs) and gene bodies, respectively. Predominantly negative association between differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were observed which implied epiregulation of DEGs. Two MADS-box genes that were significantly downregulated by long photoperiod showed significant hypermethylation in promoter regions that is essentially TE-rich. This study indicates MADS-box genes which are partially regulated by promoter methylation state may mediate photoperiod-dependent regulation of cucumber sex expression.

https://ift.tt/2ABpSMh

The Yeast DNA Damage Checkpoint Kinase Rad53 Targets the Exoribonuclease, Xrn1

The highly conserved DNA damage response (DDR) pathway monitors the genomic integrity of the cell and protects against genotoxic stresses. The apical kinases, Mec1 and Tel1 (ATR and ATM in human, respectively), initiate the DNA damage signaling cascade through the effector kinases, Rad53 and Chk1, to regulate a variety of cellular processes including cell cycle progression, DNA damage repair, chromatin remodeling, and transcription. The DDR also regulates other cellular pathways, but direct substrates and mechanisms are still lacking. Using a mass spectrometry-based phosphoproteomic screen in Saccharomyces cerevisiae, we identified novel targets of Rad53, many of which are proteins that are involved in RNA metabolism. Of the 33 novel substrates identified, we verified that 12 are directly phosphorylated by Rad53 in vitro: Xrn1, Gcd11, Rps7b, Ded1, Cho2, Pus1, Hst1, Srv2, Set3, Snu23, Alb1, and Scp160. We further characterized Xrn1, a highly conserved 5' exoribonuclease that functions in RNA degradation and the most enriched in our phosphoproteomics screen. Phosphorylation of Xrn1 by Rad53 does not appear to affect Xrn1's intrinsic nuclease activity in vitro, but may affect its activity or specificity in vivo.

https://ift.tt/2ESeZK7

Few Smokers With PAD Receive Adequate Cessation Support

TUESDAY, Oct. 30, 2018 -- More than one-third of patients with peripheral artery disease (PAD) are active smokers, yet few of them receive evidence-based smoking cessation interventions, according to a study published in the Oct. 16 issue of the...

https://ift.tt/2ABaSy0

Peer Support Aids Patients With T2DM, Depressive Symptoms

TUESDAY, Oct. 30, 2018 -- Peer support reduces hospitalizations for diabetes patients with depressive symptoms, according to a study published online Oct. 29 in Diabetes Care. Andrea L. Cherrington, M.D., M.P.H., from the University of Alabama at...

https://ift.tt/2EPUoG8

AMA Announces Initiative to Reinvent Physician Training

TUESDAY, Oct. 30, 2018 -- The American Medical Association (AMA) today announced a new $15 million competitive grant initiative, the "Reimagining Residency" initiative, aimed at improving residency training. The AMA will award $15 million over five...

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The American Society for Radiation Oncology, Oct. 21-24

The 60th Annual Meeting of the American Society for Radiation Oncology The annual meeting of the American Society for Radiation Oncology was held from Oct. 21 to 24 in San Antonio, Texas, and attracted approximately 11,000 participants from around...

https://ift.tt/2ERIxY9

Erectile Dysfunction Common in Childhood Cancer Survivors

TUESDAY, Oct. 30, 2018 -- The prevalence of erectile dysfunction (ED) is 29 percent among male childhood cancer survivors (CCS), according to a research letter published online Oct. 4 in JAMA Oncology. Laura van Iersel, M.D., from St. Jude...

https://ift.tt/2ABaRtW

Right time and place for IL-12: targeted delivery stimulates immune therapy

Systemic interleukin 12 therapy has potent antitumor effects, but clinical delivery of this potent cytokine has been complicated by systemic toxicity. A novel strategy to deliver IL-12 to the tumor microenvironment appears promising in a first-in-human study, appearing to stimulate tumor specific adaptive immune responses with minimal systemic toxicity.

https://ift.tt/2ACcJT5

Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan-kynurenine-aryl hydrocarbon axis

Significant progress has been made in cancer immunotherapy with checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)-programmed death-ligand 1 signaling pathways. Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on treatment. Not all tumors with this phenotype respond however and one mediator of immunosuppression in T cell-inflamed tumors is the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) pathway. Multiple mechanisms of immunosuppression may be mediated by this pathway including depletion of tryptophan, direct immunosuppression of Kyn and activity of Kyn-bound AhR. Indoleamine 2,3-dioxygenase 1 (IDO1), a principle enzyme in Trp catabolism, is the target of small molecule inhibitors in clinical development in combination with PD-1 checkpoint inhibitors. Despite promising results in early phase clinical trials in a range of tumor types, a phase III study of the IDO1-selective inhibitor epacadostat in combination with pembrolizumab showed no difference between the epacadostat-treated group versus placebo in patients with metastatic melanoma. This has led to a diminution of interest in IDO1 inhibitors however other approaches to inhibit this pathway continue to be considered. Novel Trp-Kyn-AhR pathway inhibitors such as Kyn degrading enzymes, direct AhR antagonists and tryptophan mimetics are advancing in early stage or pre-clinical development. Despite uncertainty surrounding IDO1 inhibition, ample preclinical evidence supports continued development of Trp-Kyn-AhR pathway inhibitors to augment immune-checkpoint and other cancer therapies.

https://ift.tt/2EUmOz4

Occurrence and significance of pathogenicity and fitness islands in environmental vibrios

Pathogenicity islands (PAIs) are large genomic regions that contain virulence genes, which aid pathogens in establishing infections. While PAIs in clinical strains (strains isolated from a human infection) are...

https://ift.tt/2PtCgWS

Respiratory failure, non-invasive ventilation and symptom burden: an observational study

Non-invasive ventilation(NIV) is commonly used to manage acute respiratory failure due to decompensated cardiorespiratory disease. We describe symptom burden in this population.

https://ift.tt/2RpolhP

The effectiveness of music therapy for terminally ill patients：A meta-analysis and systematic review

The quality of death has increasingly raised concern because of the physical and psychological suffering of patients with advanced disease. Music therapy has been widely used in palliative care; however, its physical and mental effectiveness remains unclear.

https://ift.tt/2PyBfg0

Immune dysregulation in cancer patients developing immune-related adverse events

https://ift.tt/2P1GUMa

Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer

https://ift.tt/2CPvoMM

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer

https://ift.tt/2OX6C4y

Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations

https://ift.tt/2CRBfB9

Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma

https://ift.tt/2P3gUQV

Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer

https://ift.tt/2CRZ2B1

Resting frontal EEG asymmetry in adolescents with major depression: impact of disease state and comorbid anxiety disorder

Major Depression (MD) is a severe mental disorder with lifetime prevalence rates of 17% (Kessler et al., 2005), mostly beginning between the ages of 12-18 years (Zisook et al., 2007). Up to 75% of children and adolescents with MD are affected by a depressive disorder as adults (Fombonne et al., 2001). Apart from the well-known diagnostic symptoms such as depressive mood (American Psychiatric Association, 2013), MD is also associated with abnormal approach and withdrawal tendencies (Derntl et al., 2011; Radke et al., 2014), which are reflected in aberrant cognition and behavior, such as e.g.

https://ift.tt/2RoeGIo

Fibromyalgia: increased reactivity of the muscle membrane and a role of central regulation

Fibromyalgia (FM) is a chronic pain condition of unknown etiology and unclear pathophysiology. FM is characterized by widespread, especially tendomuscular, pain and generalized hypersensitivity to pain (Mease, 2005; Wolfe and Rasker, 2013; Yunus, 2008). There is evidence of hyperactivation/deregulation at various levels of the central nervous system (Banic et al., 2004; Burgmer et al., 2012; Choi et al., 2016; Desmeules et al., 2003; Gracely et al., 2002; Truini et al., 2015; Yunus, 2008). In addition, there is growing evidence of muscular function disturbance (Ge et al., 2009; Hubbard and Berkoff, 1993; Klaver-Krol, 2017; Vitali et al., 1989).

https://ift.tt/2Px2SpZ

Electrophysiological evidence for changes in attentional orienting and selection in functional somatic symptoms

Medically unexplained symptoms (MUS) or functional somatic symptoms are characterised by unpleasant physical sensations with medical characteristics that do not correspond adequately to any acknowledged medical impairment. The nature of symptoms greatly varies, ranging from headaches, joint weaknesses, back pains, and heart palpitation, to severe cases of temporal blindness, motor paralysis, and even epileptic seizure. However, the underlying cause of MUS remains largely unknown (APA, 2013; Hatcher and Arrol, 2008).

https://ift.tt/2RoeAAw

Predictive Value of Intraoperative Bulbocavernosus Reflex during Untethering Surgery for Post-operative Voiding Function

Tethered cord syndrome (TCS) occurs as a result of inelastic structures anchoring the cord. Clinical presentation varies by age, but loss of bladder or bowel control, motor weakness, sensory loss, scoliosis, spasticity, and pain can develop (Frainey et al. 2014). Particularly, sacral function, including bladder and bowel control, as well as sexual function, is one of the major considerations because of its close relationship with quality of life. For treatment, surgical release of the tethered cord is recommended in early diagnosis to prevent functional deterioration (Solmaz et al.

https://ift.tt/2PurbF6

PREDICTORS OF HEPATOCELLULAR CARCINOMA IN HCV CIRRHOTIC PATIENTS TREATED WITH DIRECT ACTING ANTIVIRALS

Despite the dramatic improvement in viral eradication rates that has been reached with direct antiviral agents (DAAs), the real benefit of viral eradication after DAAs on hepatocellular carcinoma (HCC) development is still controversial.

https://ift.tt/2Sxfegj

Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma

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Directory: AAO Officers and Organizations

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Second molar intrusion: Continuous arch or loop mechanics?

Our aim was to compare the load systems produced by rectangular loops and continuous arch mechanics on intrusion of a maxillary second molar.

https://ift.tt/2qhPg3s

Information for readers

https://ift.tt/2Q7ewVo

Comparative assessment of bonding time and 1-year bracket survival using flash-free and conventional adhesives for orthodontic bracket bonding: A split-mouth randomized controlled clinical trial

A new flash-free adhesive promises to eliminate the flash removal step in bonding and to reduce bonding time by as much as 40% per bracket, with a bond failure rate of less than 2%. The aim of this trial was to compare bonding time and bracket failure rate over a 1-year period between the flash-free adhesive and a conventional adhesive for orthodontic bracket bonding.

https://ift.tt/2qhPeZo

Editorial Board

https://ift.tt/2Q5J5e9

Root resorption of maxillary incisors after traction of unilateral vs bilateral impacted canines with reinforced anchorage

The aim of this study was to compare the root resorption (RR) of maxillary incisors after traction of unilateral vs bilateral impacted canines with reinforced anchorage.

https://ift.tt/2qhPcAK

Table of Contents

https://ift.tt/2QeDMsQ

ASA Ruling on OrthoAccel Technologies Inc t/a AcceleDent

Upheld Internet (on own site) 04 July 2018

https://ift.tt/2qlI4ne

A recipe for conflict

Brian has been a difficult patient from the outset of his treatment. He is the son of 2 busy attorneys, who appear to prioritize their careers over family obligations. An ambivalent 13-year-old, Brian has displaced multiple brackets since he began comprehensive correction almost 3 years ago. You've met repeatedly with his father to discuss the need for more prudent eating habits and to request that he refrain from chewing on pencils. Another problem is his home care. Apparently, it doesn't exist.

https://ift.tt/2Q6LpBO

Three-dimensional evaluation of open-bite patients treated with anterior elastics and curved archwires

One nonsurgical treatment method for a patient with open bite is to use curved nickel-titanium arches and anterior elastics. The aim of this study was to investigate the effects of this technique with cone-beam computed tomography.

https://ift.tt/2qhPAPT

A daughter's question: Asked and answered

Back in 2011, I was invited to offer an opinion article for a special issue of the Southern Association of Orthodontists News.1 Many others were similarly invited, including David Sarrett (dean of a new dental school), and the likes of Johnston, Joondeph, Lindauer, Sadowsky, Cangialosi, Kluemper, Beeman, Hartsfield, Huja, Trojan, Casko, and Will. At the time, there were many big issues on the table that were both disturbing and challenging. They included the opening of many new dental schools, problems related to the recruitment and retention of faculty, how many practitioners were needed, serving the underserved (ie, access to care), increasing the quality of dental education and scholarly accomplishment, inadequate dental school funding, the cost of education, and increasing student debt.

https://ift.tt/2Q7XuGX

Morphologic and gene expression analysis of periodontal ligament fibroblasts subjected to pressure

Force application (FA) during orthodontic tooth movement is mediated through periodontal ligament (PDL) fibroblasts. FA on deciduous teeth has an inherent risk of root resorption, which is less in permanent teeth. Currently, the root resorption mechanism is poorly understood. We hypothesized that FA alters the morphology and gene expression of PDL fibroblasts. This study was designed to achieve homogenous PDL fibroblast cultures, establish an in-vitro FA model, analyze fibroblast morphology after FA, and compare the gene expressions of PDL fibroblasts of deciduous and permanent teeth after FA.

https://ift.tt/2qkzK7i

Authors' response

The range of our scoping review literature search was 2004 through May 2017; over 1 year later, the peer review process was complete, and the article was published. So it is no surprise that more articles have been published since we completed our search, and we are glad to learn of the 2 mentioned by Dr Hudson. We wonder, however, whether Dr. Hudson has correctly interpreted the meaning of those articles. To clarify this matter, we contacted Dr Manfredini, whose works are extensively cited to support Dr Hudson's arguments.

https://ift.tt/2Q83M9i

Patient satisfaction and quality of life status after 2 treatment modalities: Invisalign and conventional fixed appliances

Our objectives were to assess patient satisfaction and quality of life among adults via 2 validated comprehensive questionnaires and to compare patient satisfaction and status in oral health-related quality of life immediately after orthodontic treatment in patients treated with Invisalign (Align Technology, San Jose, Calif) and those who received standard bracket-based treatment.

https://ift.tt/2qlhUB4

Widening the scope

I want to thank Drs Rinchuse and Greene for their article, "Scoping review of systematic review abstracts about temporomandibular disorders: comparison of search years 2004 and 2017" (Rinchuse DJ, Greene CS. Am J Orthod Dentofacial Orthop 2018;154:35-46). This was an interesting way to bring our members more up to date with the plethora of TMD systematic reviews that are now coming out and the implications of the important recent advances in the field. The role of genetics in our understanding and identification of vulnerable patients is an exciting movement.

https://ift.tt/2Q8mldI

Accuracy of 3-dimensional printed dental models reconstructed from digital intraoral impressions

A rapidly advancing digital technology in orthodontics is 3-dimensional (3D) modeling and printing, prompting a transition from a more traditional clinical workflow toward an almost exclusively digital format. There is limited literature on the accuracy of the 3D printed dental models. The aim of this study was to assess the accuracy of 2 types of 3D printing techniques.

https://ift.tt/2qix61x

November 2018:154(5)

https://ift.tt/2QeDJxa

Orthodontic correction of severe Class II malocclusion in a patient with Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a complex disorder that affects multiple systems and may cause craniofacial and dentofacial abnormalities. However, there is still a lack of evidence in the literature regarding the progress of orthodontic treatment in patients with PWS. This case report describes the successful orthodontic treatment of a patient with PWS. A girl, 9 years 0 months of age, who had been diagnosed with PWS had protruding maxillary incisors and a convex profile. Her malocclusion was due to the posteriorly positioned mandible.

https://ift.tt/2qlhVF8

Authors' response

As we have mentioned several times in our previous articles including our most recently published work, (Chan E, Dalci O, Petocz P, Papadopoulou AK, Darendeliler MA. Physical properties of root cementum: part 26. Effects of micro-osteoperforations on orthodontic root resorption: a microcomputed tomography study. Am J Orthod Dentofacial Orthop 2018; 153:204-13), we believe that the effects of different treatment procedures or other interventions on root resorption should be evaluated in patients who are undergoing full-length orthodontic treatment.

https://ift.tt/2QcTV2k

Excluded unless essential

You have decided to be an expert witness in an orthodontic malpractice case. For which side is irrelevant, but for our purposes, let's say that you're testifying for the defendant. The defense attorney has decided that some testimony from one of the plaintiff's key experts will be critical to the outcome of the case, and so he asks you to sit in the courtroom gallery to listen to the testimony of the plaintiff's expert. This will allow you to better refute his or her opinion. McAbee v Chapman, No.

https://ift.tt/2qi2cGG

Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case–Control Study

Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case–control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC).

https://ift.tt/2OgOldj

A Joint Approach to Immunotherapy Biomarkers [News in Brief]

Tumor mutational burden and inflammatory gene signature independently predict responses to pembrolizumab.

https://ift.tt/2yJ9AQ3

Cemiplimab Approved for Treatment of CSCC [News in Brief]

PD-1 inhibitor is first effective treatment for patients with metastatic or locally advanced disease.

https://ift.tt/2OcFjhu

Plasma-Based Genotyping Pays Off in NSCLC [News in Brief]

Done alone or with tissue genotyping, it can predict effective targeted therapies for many patients.

https://ift.tt/2yCJBK0

Chief John M. Buckman III joins IamResponding as Director of Government and Regional Outreach

Dewitt, New York - IamResponding.com is pleased to announce that Chief John M. Buckman III has joined the IamResponding team as its new Director of Government and Regional Outreach. IamResponding is excited to have Chief Buckman join its team of emergency services professionals and looks forward to working with Chief Buckman to enhance its current product offerings, and to expand its current...

https://ift.tt/2Og5weY

Nuchal Rigidity in Infantile Bacterial Meningitis

A 1-year-old boy presented with a 2-day history of fever and vomiting. His vaccination status was up to date, including 4 doses of the 13-valent pneumococcal conjugate vaccines and Hemophilus influenza type b vaccines. At presentation, there were no physical signs suggesting respiratory or circulatory compromise. His heart rate and respiratory rate were 150 beats per minute and 44 times per minute, respectively. His body temperature was 39.6°C. There was no paralysis, and the pupillary light reflex was normal.

https://ift.tt/2yCEs4E

Prognostic role of BAP-1 and PBRM-1 expression in intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC. miR-31 seems also to play important regulatory functions in ICC and it directly regulates BAP-1 expression in lung cancer. In this study, tissue expression of BAP-1, PBRM-1, S100P, and miR-31 was investigated in ICC and correlated with clinical-pathological features. Sixty-one consecutive patients who underwent curative hepatic resection for ICC were enrolled. None received any therapy prior to surgery. Immunostaining for BAP-1, PBRM-1, and S100P, and in situ hybridization for miR-31 were performed, using tissue microarray slides. A strong retained expression of BAP-1 and PBRM-1 was associated with a reduced overall (p = 0.04 and p = 0.002, respectively) and disease-free survival (p = 0.05 and p = 0.02, respectively). An overexpression of S100P was related to a reduced overall survival (p = 0.005). The multivariate analyses identified the presence of perineural invasion and the retained PBRM-1 expression as independent predictors of worse overall [p = 0.02, hazard ratio (HR) = 2.25 (1.16–4.39) and p = 0.001, HR = 3.13 (1.56–6.28), respectively] and disease-free survivals [p = 0.03, HR = 2.43 (1.09–5.4) and p = 0.03, HR = 2.51 (1.11–5.67), respectively]. An overexpression of S100P was predictive of a worse overall survival [p = 0.02, HR = 1.66 (1.08–2.55)]. High levels of miR-31 were significantly associated to a low expression of BAP-1 protein (p = 0.03). In ICC, a retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis.

https://ift.tt/2SqdDJn

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

A modified Steglich esterification reaction was used to synthesize a small library of ester derivatives with primary and secondary alcohols. The methodology uses a non-halogenated and greener solvent, acetonitrile, and enables product isolation in high yields without the need for chromatographic purification.

https://ift.tt/2P20LuU

The aftermath of boxing revisited: identifying chronic traumatic encephalopathy pathology in the original Corsellis boxer series

https://ift.tt/2qiWJ2n

Chromium in Postmortem Material

Abstract

Recently, considerable attention has been paid to the negative effects caused by the presence and constant increase in concentration of heavy metals in the environment, as well as to the determination of their content in human biological samples. In this paper, the concentration of chromium in samples of blood and internal organs collected at autopsy from 21 female and 39 male non-occupationally exposed subjects is presented. Elemental analysis was carried out by an electrothermal atomic absorption spectrometer after microwave-assisted acid digestion. Reference ranges of chromium in the blood, brain, stomach, liver, kidneys, lungs, and heart (wet weight) in the population of Southern Poland were found to be 0.11–16.4 ng/mL, 4.7–136 ng/g, 6.1–76.4 ng/g, 11–506 ng/g, 2.9–298 ng/g, 13–798 ng/g, and 3.6–320 ng/g, respectively.

https://ift.tt/2OWofS5

Mercury Bioaccumulation in Tropical Mangrove Wetland Fishes: Evaluating Potential Risk to Coastal Wildlife

Abstract

The present study, aimed at observing the total concentration of mercury (Hg) in edible finfish species with an implication to human health risk, was carried out from the Setiu mangrove wetlands on the east coast of Peninsular Malaysia. Out of 20 species observed, the highest Hg concentrations were found among carnivores-fish/invertebrate-feeders, followed by omnivores and carnivores-invertebrate-feeders, while the lowest concentrations in herbivores. The Hg concentrations varied widely with fish species and body size, from 0.12 to 2.10 mg/kg dry weight. A positive relationship between body weight and Hg concentration was observed in particular for Toxotes jaculatrix and Tetraodon nigroviridis. Besides the permissible range of Hg concentration up to 0.3 mg/kg (cf. United States Environmental Protection Agency (USEPA)) in majority of species, the carnivore feeders such as Acanthopagrus pacificus, Gerres filamentosus, and Caranx ignobilis have shown excess amounts (> 0.40 mg/kg flesh weight) that raising concerns over the consumption by local people. However, the weekly intake of mercury—estimated through the fish consumption in all three trophic levels—suggests that the present Hg concentrations are still within the range of Provisional Tolerable Weekly Intake (PTWI) reported by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Perhaps, a multi-species design for Hg monitoring at Setiu wetlands would be able to provide further insights into the level of toxicity transfer among other aquatic organisms and thereby a strong health risk assessment for the local communities.

https://ift.tt/2CRmLBp

Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells

Abstract

This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0 μmol Se/L) for 2 h, followed by LPS (100 ng/mL) stimulation for another 3 h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100 ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P < 0.05) mRNA profiles of 9 inflammation-related genes in cells, while short-time Se pretreatment modestly reversed (P < 0.05) the LPS-induced upregulation of 7 genes (COX-2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, and MCP-1) and further increased (P < 0.05) expression of IFN-β and TNF-α in stressed cells. Meanwhile, LPS decreased (P < 0.05) mRNA levels of 18 selenoprotein encoding genes and upregulated mRNA levels of TXNRD1 and TXNRD3 in cells. Se pretreatment recovered (P < 0.05) expression of 3 selenoprotein encoding genes (GPX1, SELENOH, and SELENOW) in a dose-dependent manner and increased (P < 0.05) expression of another 5 selenoprotein encoding genes (SELENOK, SELENOM, SELENOS, SELENOT, and TXNRD2) only at a high level (2.0 μmol Se/L). Taken together, LPS-induced immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.

https://ift.tt/2OWDr1w

Correction to: Impact of Prenatal and Postnatal Treatment of Sodium Fluoride and Aluminum Chloride on Some Hormonal and Sensorimotor Aspects in Rats

The original version of this article contained a mistake: The author name Ahood A. Al-Eidan was incorrectly written as Ahoud A. Al-Eidan.

https://ift.tt/2CSfRfi

Associations Between Copper and Zinc and Risk of Hypertension in US Adults

Abstract

Evidence linking copper and zinc to hypertension are limited and conflicting. Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 were used. Zinc and copper intake from diet and supplements was assessed with 24-h dietary recall. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg/diastolic blood pressure (DBP) ≥ 90 mmHg/treatment with hypertensive medications. In a sensitivity analysis, according to the 2017 American College of Cardiology and American Heart Association guideline, hypertension was also defined as SBP ≥ 130 mmHg/DBP ≥ 80 mmHg/treatment with hypertensive medications. A total of 17,811 adults (8430 men and 9381 women) were included. After adjustment for age, gender, body mass index (BMI), race, educational level, smoking status, family income, and total daily energy intake, the OR of hypertension for highest vs. lowest quartile intake of copper, zinc, and copper/zinc ratio was 1.11 (0.90–1.37), 1.11 (0.90–1.35), and 0.95 (0.81–1.11), respectively. In stratified analysis by BMI (< 25 kg/m², 25–30 kg/m², > 30 kg/m²), no significant association was found between hypertension and intakes of copper, zinc, and copper/zinc ratio (highest vs. lowest quartile) in multivariate analysis. In multivariate analysis, the OR of hypertension for highest vs. lowest quartile levels of serum copper, zinc, and copper/zinc ratio was 1.11 (0.61–2.04), 1.43 (0.84–2.44), and 0.68 (0.34–1.33), respectively. Similar results were found in the sensitivity analysis. Zinc and copper might be not independently associated with hypertension in US adults.

https://ift.tt/2OYksUu

Speciation Analysis of Trace Mercury in Sea Cucumber Species of Apostichopus japonicus Using High-Performance Liquid Chromatography Conjunction With Inductively Coupled Plasma Mass Spectrometry

Abstract

In this paper, a simple and cost-effective method using high-performance liquid chromatography in conjunction with inductively coupled plasma mass spectrometry with a rapid ultrasound-assisted extraction was used for analysis speciation of trace mercury in sea cucumber species of Apostichopus japonicus. The effective separation of inorganic mercury, methylmercury, and ethylmercury was achieved within 10 min using Agilent ZORBAX SB-C₁₈ analytical and guard columns with an isocratic mobile phase consisting of 8% methanol and 92% H₂O containing 0.12% L-cysteine (m/v) and 0.01 mol/L ammonium acetate. Mercury species were extracted from A. japonicus samples using a solution containing 2-mercaptoethanol, L-cysteine, and hydrochloric acid and sonicating for 0.5 h. The limits of detection of inorganic mercury, methylmercury, and ethylmercury were 0.12, 0.08, and 0.20 μg/L, and the minimum detectable concentrations (measured at 0.500 g sample volume in 10.00 mL) were 2.4, 1.6, and 4.0 μg/kg, respectively. Analysis of a scallop certified reference material (GBW 10024) revealed accordance between the experimental and certified values. This study provides a reference for the evaluation of mercury speciation in sea cucumber and other seafood.

https://ift.tt/2CR9poz

Zinc and Insulin Resistance: Biochemical and Molecular Aspects

Abstract

Studies have shown the participation of minerals in mechanisms involved in the pathogenesis of insulin resistance. Zinc, in particular, seems to play an important role in the secretion and action of this hormone. Therefore, the aim of this review is to understand the role of zinc in increasing insulin sensitivity. We conducted a search of articles published in the PubMed and ScienceDirect database selected from March 2016 to February 2018, using the keywords "zinc," "insulin," "insulin resistance," "insulin sensitivity," and "supplementation." Following the eligibility criteria were selected 53 articles. The scientific evidences presented in this review show the importance of zinc and their carrier proteins in the synthesis and secretion of insulin, as well as in the signaling pathway of action of this hormone. Zinc deficiency is associated with glucose intolerance and insulin resistance; however, the effectiveness of the intervention with the zinc supplementation is still inconclusive.

https://ift.tt/2P1Tlry

Metal Contents in the Most Widely Consumed Commercial Preparations of Four Different Medicinal Plants (Aloe, Senna, Ginseng, and Ginkgo) from Europe

Abstract

Medicinal plants like Aloe barbadensis, Ginkgo biloba, Panax ginseng, and Cassia angustifolia are being increasingly used but self-medication is a major public health challenge because of their numerous interactions. Furthermore, dietary exposure to metals through the consumption of these commercial preparations should be evaluated. Some of these metals may have a nutritional interest but others are metals of toxicological relevance. The content of essential and toxic metals has been analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) in 80 samples of both organically and conventionally grown aloe, senna, ginseng, and ginkgo pharmaceutical formats to establish their metallic profile, to evaluate their nutritional value and to assess the toxic metal risk resulting from their consumption. Ca (9181 mg/kg ww) in senna, Fe (30.0 mg/kg ww) in ginseng, and Al (15.7 mg/kg ww) in ginseng are noteworthy. The consumption of 9 g/day of ginkgo represents 6.44% of the RDI set for Ca. The consumption of 25 mL/day of aloe syrup is 3.06% (men) and 1.52% (women) of the RDI of Fe. Al exposure from 25 mL/day of aloe consumption is 2.71% of its TDI. Considering the dosages recommended by the manufacturers, the intake of toxic metals does not pose a health risk but the intake of essential metals is worth mentioning.

https://ift.tt/2CR9mZV

Effect of Aluminum Exposure on Glucose Metabolism and Its Mechanism in Rats

Abstract

The effects of aluminum (Al) exposure on glucose metabolism and its mechanism were investigated. A total of 30 healthy Wistar male rats were randomly divided into two groups: control (GC) and experimental (GE). The GC group received intraperitoneal normal saline. The GE was established by intraperitoneal injected AlCl₃ solution at 10 mg/kg for 30 days. Fasting blood glucose (FBG) and serum levels of insulin (FINS) were measured. The insulin resistance index (HOMA-IR) and pancreatic β cell function index (HOMA-β) were calculated and analyzed with homeostasis model assessment (HOMA). Pancreatic tissue was taken for pathological examination. Glucose transporter 4 (GLUT4) expression in skeletal muscle was detected by quantitative PCR and Western blot. Levels of FBG and HOMA-IR in GE were higher than those in GC at day 10 and 20 (P < 0.05). FINS in GE were higher than those in GC at day 10 and 20, and lower than those in GC at day 30 (P < 0.05). HOMA-β in GE was lower than that of GC at every time point (P < 0.05). Pathology showed that pancreatic damage changed more profoundly with prolongation of time in GE. Expression levels of GLUT4 mRNA and protein in rat skeletal muscle in GE were significantly lower than those in GC (P < 0.05). The results suggested that Al exposure affected glucose metabolism through pancreatic damage and reduction of GLUT4 expression.

https://ift.tt/2OYkqfk

Impact of Prenatal and Postnatal Treatment of Sodium Fluoride and Aluminum Chloride on Some Hormonal and Sensorimotor Aspects in Rats

Abstract

In most communities, there is a constant exposure to environmental pollutants with probable negative impact on the development of the nervous system. Among these pollutants are the sodium fluoride (NaF) and aluminum chloride (AlCl₃) which may represent a real threat to the proper functioning of the brain. This study comprises two fundamentally different strategies; in the first one, pregnant rats were administered a daily dose of NaF (0.15 g /L) or AlCl₃ (500 mg/L) in the drinking water either separately or in combination with each other from day 6 of gestation until just after weaning. In the second approach, the male rats born to mothers exposed to the pollutants were divided into two groups. In the first, rats were continued to be treated with the same pollutants administered to them in the drinking water at the same dose level until the age of 70 days. The rats of the second group were supplied with drinking water without either one of the pollutants for a similar period of time. The rats exposed to NaF separately or in combination with AlCl₃ during the prenatal life and subsequently through the postnatal stages exhibited disturbance in the locomotor activities. This was concomitant with alterations in plasma, PTH, ACTH, and estradiol levels. Additionally, the serum levels of LH and testosterone were altered in the two groups treated with sodium fluoride during the prenatal and up to the weaning periods or in the group which continued to have the NaF until day 70 after birth.

https://ift.tt/2CR98C3

Response to Letter to the Editor: “Comment on “Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet””

https://ift.tt/2OZKoz3

Effect of Lead on Antioxidant Ability and Immune Responses of Crucian Carp

Abstract

The aim of this study was to explore the effects of lead exposure on the antioxidant and immune responses of Crucian carp. Three hundred sixty healthy Crucian carp were randomly grouped into four groups and exposed to different doses of lead (0, 0.05, 0.5, and 1 mg/L). Fish were sampled at 30 and 60 days, respectively, and antioxidant capability, immune parameters, ALAD activity, and immune-related genes were assessed. The results showed that T-AOC and GSH activities of the liver were significantly increased in 60 days (P < 0.05); the activities of SOD, CAT, T-AOC, and GSH were significantly increased (P < 0.05) compared to the control in the kidney in 60 days. With an increase in Pb dose, the activity and expression of lysozyme and the content of immunoglobulin M were significantly decreased compared to the control. Compared with the control group, the activity of ALAD in the lead-exposed group decreased significantly (P < 0.05). The expression of the HSP70, tumor necrosis factor-α (TNF-α), interleukins (IL-10), and immunoglobulin M genes was all enhanced in lead-exposed group, whereas lysozyme gene expression was decreased. The results indicated that lead induced oxidative stress and had immunotoxic effects on Crucian carp.

https://ift.tt/2CR90T5

Selenium-Rich Yeast Protects Against Aluminum-Induced Renal Inflammation and Ionic Disturbances

Abstract

The aim of this study was to evaluate the protective effects of SeY (selenium-rich yeast) against Al (aluminum)-induced inflammation and ionic imbalances. Male Kunming mice were treated with Al (10 mg/kg) and/or SeY (0.1 mg/kg) by oral gavage for 28 days. The degree of inflammation was assessed by mRNA expression of inflammatory biomarkers. Ionic disorders were assessed by determining the Na⁺, K⁺, and Ca²⁺ content, as well as the alteration in ATP-modifying enzymes (ATPases), including Na⁺K⁺-ATPase, Ca²⁺-ATPase, Mg²⁺-ATPase, Ca²⁺Mg²⁺-ATPase, and the mRNA levels of ATPase's subunits in kidney. It was observed here that SeY exhibited a significant protective effect on the kidney against the Al-induced upregulation of pro-inflammatory and downregulation of anti-inflammatory cytokines. Furthermore, a significant effect of Al on the Na⁺, K⁺, Ca²⁺, and Mg²⁺ levels in kidney was observed, and Al was observed to decrease the activities of Na⁺K⁺-ATPase, Mg²⁺-ATPase, and Ca²⁺Mg²⁺-ATPase. The mRNA expression of the Na⁺K⁺-ATPase subunits and Ca²⁺-ATPase subunits was regulated significantly by Al. Notably, SeY modulated the Al-induced alterations of ion concentrations, ATPase activity, and mRNA expression of their subunits. These results suggest that SeY prevents renal toxicity caused by Al via regulation of inflammatory responses, ATPase activities, and transcription of their subunits.

https://ift.tt/2OX7OF8

Changes in Trace Elements During Early Stages of Chronic Kidney Disease in Type 2 Diabetic Patients

Abstract

Trace elements can influence glucose metabolism and be related to oxidative stress in type 2 diabetes mellitus. Moreover, trace elements play important roles in the nephrotic complications of these patients. Nevertheless, few investigations have been made into the changes in the levels of trace elements in diabetic patients at various stages of chronic kidney disease (CKD). The aims of this present study were to determine the levels of some important trace elements in diabetic patients during the early stages of CKD and to identify the relationship between these elements and CKD progression in type 2 diabetic patients. One hundred and forty-eight type 2 diabetic patients with chronic kidney diseases were recruited into this study. The subjects were grouped into four stages (1, 2, 3a, 3b) of CKD, according to their urine protein levels and estimated glomerular filtration rates (eGFRs). The levels of serum zinc and iron exhibited a statistically significant decreasing trend (P trend = 0.032 and 0.047, respectively) from stage 1 to stage 3b after adjustment for age, gender, smoking, alcohol consumption, education, hypertension, and body mass index. The other tested elements, including copper, magnesium, selenium, chromium, and manganese, did not display any significant trends upon proceeding from stage 1 to stage 3b. Thus, serum zinc and iron appear to be useful markers when evaluating the early progression of CKD in type 2 diabetic patients.

https://ift.tt/2CR9usn

Determination of Trace Elements in Infant Formulas Available on Polish Market

Abstract

The aim of this study was to assess the levels of 13 essential and toxic elements (As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, V, Zn) in the infant formulas, available on Polish market. Selected food samples were of animal (cow- and goat-based milks) and plant (soy-based milk, hypoallergic products, grain porridges) origin. Two analytical techniques, inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA), have been complementarily applied to analyze elemental content of 16 formulas dedicated for infants between 0 and 8 months. For arsenic determinations, the radiochemical mode of NAA was also used. The daily intake of some micronutrients in the age 0–8 months for non-breastfed infants was estimated and compared with present safety limits. Certified reference materials (CRMs) have been used for the validation of the methods: Non-fat Milk Powder 1549 (National Bureau of Standards—NBS), Soya Bean Flour INCT-SBF-4 (Institute of Nuclear Chemistry and Technology—INCT), Rice Flour SRM 1568b (National Institute of Standards and Technology—NIST).

https://ift.tt/2CR8QLt

Alleviation Mechanisms of Selenium on Cadmium-Spiked in Chicken Ovarian Tissue: Perspectives from Autophagy and Energy Metabolism

Abstract

Cadmium (Cd) is a kind of toxic heavy metal and it can cause damage to organs and tissues. Selenium (Se) can antagonize some metal element toxicity including Cd. The present study was designed to investigate Cd-induced damage to chicken ovary by autophagy and the protective mechanism of Se on Cd-induced damage. Administration of Cd for 12 weeks led to energy metabolism disorder of the chicken ovarian tissues, which resulted in autophagy. In addition, the mRNA expression of glucose-related genes including hexokinase II (HK2), pyruvate kinase (PK), pyruvate dehydrogenase complex (PDHX), and succinate dehydrogenase (SDH) and the activities of ATPase, including Na⁺-K⁺-ATPase, Ca²⁺-ATPase, Mg²⁺-ATPase, were all downregulated remarkably compared with the control. However, combined with oral administration of Se at 2 mg/kg, the mRNA expression of glucose-related genes and the activities of ATPase increased. The mRNA expression of the autophagy-related genes by Cd treatment, including microtubule-associated protein light chain 3 (LC3), dynein, autophagy-related gene 5 (Atg5), and Beclin 1, was remarkably enhanced, whereas mammalian target of rapamycin (mTOR) was downregulated. However, besides mTOR, their levels displayed a downregulated trend beyond simultaneous Se treatment. The protein expression of autophagy genes was similar to those of mRNA. In conclusion, Cd toxicity affect energy metabolism and induce autophagy, which causes damage to chicken ovary, whereas Se could protect effectively this injury induced by Cd.

https://ift.tt/2OWmVPb

Heavy Metal (Cd and Pb) and Aflatoxin Contamination in Tissues and Eggs from Free Grazing Ducks and Their Environment in Central Thailand

Abstract

The cross-sectional study of heavy metals and aflatoxins was conducted by studying duck egg, blood, liver, feed, and water samples from 11 free grazing farms. The duck feed, soil, and rice samples were lower than the standard limit for aflatoxins at 20 ng g⁻¹. The highest levels of aflatoxin were detected in the liver, intestine, and egg yolk; these were 3.04, 1.73, and 4.56 ng g⁻¹ respectively, while the average levels were 1.6 ± 0.73, 1.31 ± 0.23, and 1.87 ± 0.99 ng g⁻¹, respectively. Interestingly, aflatoxin was not detected in any of the egg white albumin samples (90/90 samples), whereas aflatoxin contamination was predominantly found in the yolk. Additionally, the means and standard deviations of Pb and Cd found in the duck eggs were 118.61 ± 22.25 and 13.84 ± 9.06 ng g⁻¹ respectively. The maximum levels of Pb and Cd in eggs were 134.34 and 29.72 ng g⁻¹, respectively. Moreover, Pb contamination occurred in the duck liver tissue in 93.61% (88/94) of the samples, whereas Cd contamination was found in 100% (100/100). The maximum levels of Pb and Cd in the duck liver tissues were 606.16 and 22,946.20 ng g⁻¹, which was higher than those in the eggs. Pb contamination in the water from rice paddy fields after grazing was significantly higher than that in water samples taken before grazing. This is the first report of Pb and Cd contamination in blood, egg, and liver samples of free grazing ducks in Thailand.

https://ift.tt/2CR8N2f

Positive PCNA and Ki-67 Expression in the Testis Correlates with Spermatogenesis Dysfunction in Fluoride-Treated Rats

Abstract

The present study aimed to evaluate the effect of fluoride (F) on spermatogenesis in male rats. F⁻ at 50 and 100 mg/L was administered for 70 days, after which the testicular and epididymis tissues were collected to observe the histopathological structure under a light microscope. The ultrastructure of the testis and sperm was also examined via transmission electron microscopy. The apoptosis of spermatogenic cells was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of proliferation factors, namely, proliferating cell nuclear antigen (PCNA) and Ki-67, in the testicular and epididymis tissues, were assayed through immunohistochemistry. F⁻ at 50 and 100 mg/L significantly damaged the structure of the testis and epididymis, and the testis and sperm ultrastructure exhibited various changes, including mitochondrial swelling and vacuolization, and apsilated and raised sperm membrane. F treatment significantly increased spermatogenic cell apoptosis in the testis. PCNA (P < 0.01) and Ki-67 (P < 0.01) also presented positive expression in the testis. By comparison, no significant changes occurred in the epididymis. In summary, excessive F intake results in spermatogenesis dysfunction by damaging the testicular structure and inducing spermatogenic cell apoptosis in male rats. The positive expression level of PCNA and Ki-67 was a good response to spermatogenesis dysfunction.

https://ift.tt/2OX7zKe

Trace Elements in Saliva as Markers of Type 2 Diabetes Mellitus

Abstract

To analyze Mg, Ca, and Zn levels in saliva, comparing patients with type 2 diabetes mellitus and a control group of healthy subjects. This transversal, observational, clinical study included a total sample of 147 patients, 74 with type 2 diabetes mellitus and a control group of 73 healthy subjects. Socio-demographic, anthropometric, diabetological, and metabolic variables were registered. Trace elements in non-stimulated basal saliva were measured using inductively coupled plasma mass spectrometry (ICP-MS): Mg, Ca, and Zn. Concentrations of zinc, calcium, and magnesium were significantly higher in the diabetic group than the control group (p < 0.001). A relation was observed between waist circumference and high cardiovascular risk in men (based on two categories: waist circumference < 102 cm; waist circumference ≥ 102 cm), and magnesium levels in saliva (p = 0.003). Magnesium, zinc, and calcium levels in saliva could be useful markers for differentiating patients with type 2 diabetes mellitus from non-diabetics. The salivary magnesium could be used as a marker of high cardiovascular risk when associated with abdominal obesity represented by a waist circumference ≥ 102 cm in men. The present results do suggest that salivary zinc levels could act as a good marker of type 2 diabetes mellitus, in light of zinc's well-known role as a co-marker of insulin and its relationship to carbohydrate metabolism.

https://ift.tt/2CTUY3p

NaF Reduces KLK4 Gene Expression by Decreasing Foxo1 in LS8 Cells

Abstract

Decreased expression and increased phosphorylation of Forkhead box o1 (Foxo1) in ameloblasts were observed both in vivo and in vitro when treated by fluoride. The present study aims to investigate the possible relationship between Foxo1 and enamel matrix proteinases, matrix metalloproteinase 20 (MMP20), and kallikrein 4 (KLK4), in NaF-treated ameloblasts. Ameloblast-like cells (LS8 cells) were exposed to NaF at selected concentration (0/2 mM) for 24 h. Gene overexpression and silencing experiments were used to up- and down-regulate Foxo1 expression. The expression levels of Foxo1, MMP20, and KLK4 were detected by quantitative real-time PCR and western blot. Dual luciferase reporter assay was performed to evaluate the regulation of Foxo1 on the transcriptional activity of KLK4 promoter. The results showed that KLK4 expression was decreased in LS8 cells treated by NaF, while MMP20 expression was not changed. Foxo1 activation led to significantly up-regulation of KLK4 in LS8 cells under NaF condition. Knockout of Foxo1 markedly decreased klk4 expression in mRNA level, and intensified inhibition occurred in LS8 cells when combined with NaF treatment. However, the variation trend of MMP20 was not clear. Dual luciferase reporter assay showed that Foxo1 activation enhanced the transcriptional activity of KLK4 promoter. These findings suggest that the decrease of Foxo1 expression induced by high fluoride was a cause for low KLK4 expression.

https://ift.tt/2P1j8jo

New on NCI Websites for October 2018

NCI periodically provides updates on new websites and other online content of interest to the cancer community. See selected content that has been added as of October 2018.

https://ift.tt/2OWFfaO

Immunization of Adult Zebrafish for the Preclinical Screening of DNA-based Vaccines

Here we describe a protocol for the immunization of the adult zebrafish (Danio rerio) with a DNA-based vaccine and demonstrate the validation of a successful vaccination event. This method is suitable for the preclinical screening of vaccine candidates in various infection models.

https://ift.tt/2CP2ufK

Visualize Drosophila Leg Motor Neuron Axons Through the Adult Cuticle

Here we describe a protocol to visualize the axonal targeting with a florescent protein in adult legs of Drosophila by fixation, mounting, imaging, and post-imaging steps.

https://ift.tt/2OVmHHU

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Here a protocol to investigate the early effects of amyloid-β (Aβ) in the brain is presented. This shows that Aβ induces clathrin-mediated endocytosis and collapse of axonal growth cones. The protocol is useful in studying early effects of Aβ on axonal growth cones and may facilitate prevention of Alzheimer's disease.

https://ift.tt/2CUkIMG

Sepsis Alliance & NAEMT team-up to combat sepsis

Sepsis Alliance, the nation's leading sepsis organization, and the National Association of Emergency Medical Technicians (NAEMT) are proud to announce their new partnership to combat sepsis and help save lives. Sepsis is the body's life-threatening reaction to an infection. In the United States, sepsis affects 1.7 million people and takes 270,000 lives. As many as 87% of sepsis cases...

https://ift.tt/2ABqd1p

Pilot Studies May Shed Light on How to Treat Lymphedema

TUESDAY, Oct. 30, 2018 -- Treatment with ketoprofen may improve the skin biology in lymphedema, with improvements noted in histopathology and skin thickness, according to a study published online Oct. 18 in JCI Insight. Stanley G. Rockson, M.D.,...

https://ift.tt/2zcIqk7

Accepting Increased-Risk Donor Heart Tied to Higher Survival

TUESDAY, Oct. 30, 2018 -- Acceptance of a heart from an increased-risk donor (IRD) is associated with a significant survival benefit, according to a research letter published in the November issue of the Journal of the American College of...

https://ift.tt/2SujVHP

Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software

We present two analytical protocols that can be used to analyze intracranial electroencephalography data using the Statistical Parametric Mapping (SPM) software: time-frequency statistical parametric mapping analysis for neural activity, and dynamic causal modeling of induced responses for intra- and inter-regional connectivity.

https://ift.tt/2CR1urj

Choice and No-Choice Bioassays to Study the Pupation Preference and Emergence Success of Ectropis grisescens

Here, we present a protocol to investigate the pupation preference of mature larvae of Ectropis grisescens in response to soil factors (e.g., substrate type and moisture content) using choice bioassays. We also present a protocol of no-choice bioassays to determine the factors that affect the pupation behaviors and survivorship of E. grisescens.

https://ift.tt/2OYYG2M

Prenatal Exposure to Phthalates Linked to Language Delay

TUESDAY, Oct. 30, 2018 -- Prenatal exposure to phthalates is associated with language delay in children, according to a study published online Oct. 29 in JAMA Pediatrics. Carl-Gustaf Bornehag, Ph.D., from Karlstad University in Sweden, and...

https://ift.tt/2zcQiSr

Community Health Worker Intervention Beneficial

TUESDAY, Oct. 30, 2018 -- A standardized community health worker (CHW)-delivered intervention, Individual Management for Patient-Centered Targets, improves patient-perceived quality of care and reduces hospitalizations for low-income patients with...

https://ift.tt/2zgEcb1

Mortality Among Young People Declined From 1999 to 2015

TUESDAY, Oct. 30, 2018 -- Mortality rates for infants and youths generally declined in the United States from 1999 to 2015, though they remain higher than rates in Canada and England/Wales, with especially high rates among black and American...

https://ift.tt/2SxzYVw

Angiotensin-Converting Enzyme Inhibitors May Up Lung CA Risk

TUESDAY, Oct. 30, 2018 -- The use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with an increased risk for lung cancer compared with angiotensin receptor blockers, according to a study published online Oct. 24 in the...

https://ift.tt/2StqY3H

Psoriasis Linked to Increased Risk for Inflammatory Bowel Disease

TUESDAY, Oct. 30, 2018 -- Psoriasis appears to be significantly associated with inflammatory bowel disease (IBD), according to a review published online Oct. 24 in JAMA Dermatology. Yun Fu, M.D., from Chang Gung Memorial Hospital in Taiwan, and...

https://ift.tt/2SuY8jj

Therapeutic Lifestyle Intervention in Church Helpful for BP Control

TUESDAY, Oct. 30, 2018 -- A therapeutic lifestyle change (TLC) intervention plus motivational interviewing (MINT) sessions delivered in churches can reduce systolic blood pressure (BP) among blacks compared with health education (HE) alone,...

https://ift.tt/2zcIoZx

New Method Estimates Risk for Recurrence in Breast Cancer

TUESDAY, Oct. 30, 2018 -- The risk for breast cancer recurrence can be extracted using disease-specific survival data, according to a study published online Oct. 18 in Cancer Epidemiology, Biomarkers & Prevention. Angela B. Mariotto, Ph.D., from...

https://ift.tt/2zcHKuY

Guidelines Presented for Lumbar Puncture in Alzheimer's Dx

TUESDAY, Oct. 30, 2018 -- The Alzheimer's Association has released appropriate-use criteria for lumbar puncture and cerebrospinal fluid (CSF) testing in Alzheimer's disease diagnosis, according to a review article published online Oct. 10 in...

https://ift.tt/2Swm6dZ

Evidence for diversifying selection of genetic regions of encoding putative collagen-like host-adhesive fibers in Pasteuria penetrans

Abstract

Pasteuria spp. belong to a group of genetically diverse endospore-forming bacteria (phylum: Firmicutes) that are known to parasitize plant-parasitic nematodes and water fleas (Daphnia spp.). Collagen-like fibres form the nap on the surface of endospores and the genes encoding these sequences have been hypothesised to be involved in the adhesion of the endospores of Pasteuria spp. to their hosts. We report a group of seventeen unique collagen-like genes putatively encoded by Pasteuria penetrans (strain: Res148) that formed five different five different phylogenetic clusters and suggest that collagen-like proteins are an important source of genetic diversity in animal pathogenic Firmicutes including Pasteuria. Additionally, and unexpectedly, we identified a putative collagen-like sequence which had a very different sequence structure to the other collagen-like proteins but was similar to the protein sequences in Megaviruses that are involved in host-parasite interactions. We, therefore, suggest that these diverse endospore surface proteins in Pasteuria are involved in biological functions, such as cellular adhesion; however, they are not of monophyletic origin and were possibly obtained de novo by mutation or possible through selection acting upon several historic horizontal gene transfer events.

https://ift.tt/2zcVbef

Intra- and inter-field diversity of 2,4-dichlorophenoxyacetic acid-degradative plasmids and their tfd catabolic genes in rice fields of the Mekong delta in Vietnam

Abstract

The tfd genes mediating degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) differ in composition and organization in bacterial isolates from different geographical origin and are carried by different types of mobile genetic elements (MGE). It is not known whether such global diversity of 2,4-D-catabolic MGE and their tfd gene cargo is reflected in the diversity at field scale. The genomic context of 2,4-D catabolic genes of 2,4-D-degrading isolates from two rice fields with a 2,4-D application history, located in distant provinces of the Vietnam Mekong delta, was compared. All isolates were β-proteobacteria, were unique for each rice field and carried the catabolic genes on MGE. Most MGE were IncP-1β plasmids and carried tfd clusters highly similar to those of the IncP-1β plasmid pJP4, typified by two chlorophenol catabolic gene modules (tfd-I and tfd-II). IncP-1β plasmids from the same field showed small deletions and/or insertions in accessory metabolic genes. One MGE belonged to an unclassified plasmid group and carries a copy of both tfdA and tfd-II identical to those in the IncP-1β plasmids. Our results indicate intra-field evolution and inter-field exchange of 2,4-D-catabolic IncP-1β plasmids as well as the exchange of tfd genes between different plasmids within a confined local environment.

https://ift.tt/2SvOJbh

Beyond “See One, Do One, Teach One”

https://ift.tt/2zcKE2Q

Participation and yield of a population-based colorectal cancer screening programme in China

Objective

Colorectal cancer (CRC) screening has been widely implemented in many countries. However, evidence on participation and diagnostic yield of population-based CRC screening in China is sparse.

Design

The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1 381 561 eligible participants aged 40–69 years from 16 provinces in China from 2012 to 2015. 182 927 participants were evaluated to be high risk for CRC by an established risk score system and were subsequently recommended for colonoscopy. Participation rates and detection of colorectal neoplasms in this programme were reported and their associated factors were explored.

Results

25 593 participants undertook colonoscopy as recommended, with participation rate of 14.0%. High level of education, history of faecal occult blood test, family history of CRC and history of colonic polyp were found to be associated with the participation in colonoscopy screening. Overall, 65 CRC (0.25%), 785 advanced adenomas (3.07%), 2091 non-advanced adenomas (8.17%) and 1107 hyperplastic polyps (4.33%) were detected. Detection rates of colorectal neoplasms increased with age and were higher for men. More advanced neoplasms were diagnosed in the distal colon/rectum (65.2%). Several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms.

Conclusion

The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate. Our findings will provide important references for designing effective population-based CRC screening strategies in the future.

https://ift.tt/2OWvMAi

Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin

Objective

Campylobacter jejuni produces a genotoxin, cytolethal distending toxin (CDT), which has DNAse activity and causes DNA double-strand breaks. Although C. jejuni infection has been shown to promote intestinal inflammation, the impact of this bacterium on carcinogenesis has never been examined.

Design

Germ-free (GF) Apc^Min/+mice, fed with 1% dextran sulfate sodium, were used to test tumorigenesis potential of CDT-producing C. jejuni. Cells and enteroids were exposed to bacterial lysates to determine DNA damage capacity via H2AX immunofluorescence, comet assay and cell cycle assay. To examine the interplay of CDT-producing C. jejuni, gut microbiome and host in tumorigenesis, colonic RNA-sequencing and faecal 16S rDNA sequencing were performed. Rapamycin was administrated to investigate the prevention of CDT-producing C. jejuni-induced tumorigenesis.

Results

GF Apc^Min/+mice colonised with human clinical isolate C. jejuni81–176 developed significantly more and larger tumours when compared with uninfected mice. C. jejuni with a mutated cdtB subunit, mutcdtB, attenuated C. jejuni-induced tumorigenesis in vivo and decreased DNA damage response in cells and enteroids. C. jejuni infection induced expression of hundreds of colonic genes, with 22 genes dependent on the presence of cdtB. The C. jejuni-infected group had a significantly different microbial gene expression profile compared with the mutcdtB group as shown by metatranscriptomic data, and different microbial communities as measured by 16S rDNA sequencing. Finally, rapamycin could diminish the tumorigenic capability of C. jejuni.

Conclusion

Human clinical isolate C. jejuni 81–176 promotes colorectal cancer and induces changes in microbial composition and transcriptomic responses, a process dependent on CDT production.

https://ift.tt/2CSjkdt

Chronic diarrhoea: the indications for lower GI endoscopy when functional bowel disease is suspected

We read with interest the 'Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, third Edition' by Arasaradnam et al.1 Compared with the second edition, the new guidance provides more detailed and specific content which will undoubtedly aid the investigation of chronic diarrhoea both in primary and secondary care. However, we would like to clarify the authors' position on the following.

On page 9 under 'Recommendations', the authors state 'In patients with typical symptoms of functional bowel disease, normal physical examination and normal screening blood and faecal tests (calprotectin), a positive diagnosis of IBS can be made (Grade of evidence level 2, Strength of recommendation strong).'

However, on the same page, they also state 'In younger patients (under 40 years) with a normal faecal calprotectin and in whom functional bowel disease is suspected, we recommend a flexible sigmoidoscopy with biopsy (Grade of evidence level 3, Strength...

https://ift.tt/2OWvFES

Animal protein intake and hepatic steatosis in the elderly

We read with interest the work by Alferink et al,1 which reports that intake of animal protein, but not that of monosaccharides and disaccharides, was found to be independently associated with non-alcoholic fatty liver disease (NAFLD). This is a surprising finding from a well-conducted cohort study that facilitated adjustment for metabolic covariates, in addition to sociodemographics and other lifestyle factors. However, we have reservations about the generalisability of these findings to patients with NAFLD or non-alcoholic steatohepatitis (NASH).

The studied population had an average age of 70 years, which is unusual for a first presentation of NAFLD. A large retrospective study identified 52.8 years as the average age of NASH-cirrhosis.2 Given the estimated rate of disease progression in NAFLD and NASH, most patients with clinically significant NAFLD are likely to have presented before the age of 70 years.3

Table 1 of the trial shows that the...

https://ift.tt/2COQriy

Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice

Objective

The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.

Design

A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.

Results

The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.

Conclusion

The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.

Trial registration number

NCT02838732; Results.

https://ift.tt/2OWvw4i

Expression of Fluorescent Fusion Proteins in Murine Bone Marrow-derived Dendritic Cells and Macrophages

In this article, we provide a detailed protocol for the expression of fluorescent fusion proteins in murine bone marrow derived dendritic cells and macrophages. The method is based on the transduction of bone marrow progenitors with retroviral constructs followed by differentiation into macrophages and dendritic cells in vitro.

https://ift.tt/2zjsPPw

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes

Abstract

Purpose

In this study, we aimed to describe the real-life practice outcomes of pertuzumab–trastuzumab–taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.

Methods

This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.

Results

Median age was 51 (22–82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5–40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.

Conclusions

Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab–trastuzumab–taxane therapy to date.

https://ift.tt/2SwoUrq

Pulsara unveiling major new features of its platform at EMS World 2018 in Nashville

BOZEMAN, Mont. — Pulsara will be unveiling critical new elements of its technology during the EMS World Expo conference this week in Nashville. Pulsara provides a real-time communication network in hospitals and across entities and regions—driving quality improvement and better patient coordination. The technology solution is being used by regional healthcare systems across the U.S....

https://ift.tt/2qiue4T

Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer

Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer

Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer, Published online: 30 October 2018; doi:10.1038/s41419-018-1101-0

Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer

https://ift.tt/2PqijQT

The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation

The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation

The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation, Published online: 30 October 2018; doi:10.1038/s41419-018-1148-y

The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation

https://ift.tt/2RoIwMK

Postoperative morbidity of complete mesocolic excision and central vascular ligation in right colectomy: a retrospective comparative cohort study

Abstract

Background

To investigate morbidity and mortality following complete mesocolic excision (CME) and central vascular ligation (CVL) in patients undergoing right colectomy.

Methods

Data from consecutive patients undergoing elective right colectomy at a university-affiliated referral centre were retrospectively analysed. Patients who underwent conventional right-sided colonic cancer surgery (January 2001–April 2009, n = 84) were compared to patients who underwent CME/CVL (May 2009–January 2015, n = 71). The primary end point was anastomotic leak. Secondary end points were delayed gastric emptying, severe respiratory failure, mortality and length of hospital stay.

Results

No significant difference was found in the rate of anastomotic leak (1.2% in the conventional versus 5.6% in the CME/CVL group, p = 0.108). Patients in the CME/CVL group had a higher 90-day mortality rate (7.0% versus 0.0%, p = 0.019). Four out of five deceased patients suffered from aspiration with consecutive respiratory failure. There was a tendency towards delayed gastric emptying in the CME/CVL group (12.7% versus 7.1%, p = 0.246). Clavien-Dindo complication grades ≥ 2 were similar in both groups with 16 (19%) in the conventional and 15 (21.1%) in the CME/CVL group (p = 0.747). CME/CVL patients had a shorter mean length of stay with 11 versus 14 days (p <  0.001).

Conclusions

Complete mesocolic excision with central vascular ligation in right colectomy seems to have a higher aspiration rate leading to severe respiratory failure and to higher mortality compared to conventional resection methods. Patient selection for this procedure may therefore be crucial.

https://ift.tt/2Q776S4

Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme

Abstract

Background

Glioblastoma multiforme (GBM) is the common primary brain tumor classified the most malignant glioma. Long non-coding RNAs (LncRNAs) are important epigenetic regulators with critical roles in cancer initiation and progression. LncRNA HOTAIRM1 transcribes from the antisense strand of HOXA gene cluster which locus in chromosome 7p15.2. Recent studies have shown that HOTAIRM1 is involved in acute myeloid leukemia and colorectal cancer. Here we sought to investigate the role of HOTAIRM1 in GBM and explore its mechanisms of action.

Methods

The expressions of HOTAIRM1 and HOXA1 in GBM tissues and cells were determined by qRT-PCR, and the association between HOTAIRM1, HOXA1 transcription and tumor grade were analyzed. The biological function of HOTAIRM1 in GBM was evaluated both in vitro and in vivo. Chromatin immunoprecipitation (ChIP) assay and quantitative Sequenom MassARRAY methylation analysis were performed to explore whether HOTAIRM1 could regulate histone and DNA modification status of the HOXA1 gene transcription start sites (TSS) and activate its transcription. ChIP and RNA-ChIP were further performed to determine the molecular mechanism of HOTAIRM1 in epigenetic regulation of the HOXA1 gene.

Results

HOTAIRM1 was abnormally up-regulated in GBM tissues and cells, and this up-regulation was correlated with grade malignancy in glioma patients. HOTAIRM1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. In vivo experiments showed knockdown of HOTAIRM1 lessened the tumor growth. Additionally, HOTAIRM1 action as regulating the expression of the HOXA1 gene. HOXA1, as an oncogene, it's expression levels were markedly elevated in GBM tissues and cell lines. Mechanistically, HOTAIRM1 mediated demethylation of histone H3K9 and H3K27 and reduced DNA methylation levels by sequester epigenetic modifiers G9a and EZH2, which are H3K9me² and H3K27me³ specific histone methyltransferases, and DNA methyltransferases (DnmTs) away from the TSS of HOXA1 gene.

Conclusions

We investigated the potential role of HOTAIRM1 to promote GBM cell proliferation, migration, invasion and inhibit cell apoptosis by epigenetic regulation of HOXA1 gene that can be targeted simultaneously to effectively treat GBM, thus putting forward a promising strategy for GBM treatment. Meanwhile, this finding provides an example of transcriptional control over the chromatin state of gene and may help explain the role of lncRNAs within the HOXA gene cluster.

https://ift.tt/2zop2Rl

Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial

Abstract

Background

This was a prespecified secondary analysis of a randomized trial that analyzed bone density and pain response following fractionated intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) for palliative management of spinal metastases.

Methods/materials

Sixty patients were enrolled in the single-institutional randomized exploratory trial, randomly assigned to receive IMRT or 3DCRT (30 Gy in 10 fractions). Along with pain response (measured by the Visual Analog Scale (VAS) and Chow criteria), quantitative bone density was evaluated at baseline, 3, and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures.

Results

Relative to baseline, bone density increased at 3 and 6 months following IMRT by a median of 24.8% and 33.8%, respectively (p < 0.01 and p = 0.048). These figures in the 3DCRT cohort were 18.5% and 48.4%, respectively (p < 0.01 for both). There were no statistical differences in bone density between IMRT and 3DCRT at 3 (p = 0.723) or 6 months (p = 0.341). Subgroup analysis of osteolytic and osteoblastic metastases showed no differences between groups; however, mixed metastases showed an increase in bone density over baseline in the IMRT (but not 3DCRT) arm. The 3-month rate of the pathological fractures was 15.0% in the IMRT arm vs. 10.5% in the 3DCRT arm. There were no differences in pathological fractures at 3 (p = 0.676) and 6 (p = 1.000) months. The IMRT arm showed improved VAS scores at 3 (p = 0.037) but not 6 months (p = 0.430). Using Chow criteria, pain response was similar at both 3 (p = 0.395) and 6 (p = 0.732) months.

Conclusions

This the first prospective investigation evaluating the impact of IMRT vs. 3DCRT on bone density. Along with pain response and pathologic fracture rates, significant rises in bone density after 3 and 6 months were similar in both cohorts. Future randomized investigations with larger sample sizes are recommended.

Trial registration

NCT, NCT02832830. Registered 14 July 2016

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