Labor Pain's Relationship With Depression: From Whence, and What Shall be Done?

No abstract available

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Dexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis

BACKGROUND: Both dexamethasone and dexmedetomidine are effective peripheral nerve block (PNB) perineural adjuncts that prolong block duration. However, each is associated with side effects. With paucity of head-to-head comparisons of these adjuncts, the question of the best adjunct to mix with local anesthetics (LA) for PNB is unanswered. This meta-analysis aims to inform current practice and future research by identifying the superior adjunct by comparing dexamethasone and dexmedetomidine. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, trials comparing the combination of perineural dexamethasone or dexmedetomidine with LA to LA alone for PNB were sought. The Cochrane Risk of Bias Tool was used to assess the methodological quality of trials, and indirect or network meta-analyses using random-effects modeling were planned. We designated duration of analgesia as a primary outcome. Secondary outcomes included sensory and motor block durations, sensory and motor block onset times, and the risks of hypotension, sedation, and neurological symptoms. RESULTS: Fifty trials were identified, including only 1 direct comparison, precluding a network meta-analysis. Indirect meta-analysis of 49 trials (3019 patients) was performed. Compared to dexmedetomidine, dexamethasone prolonged the duration of analgesia by a mean difference (95% confidence interval [CI]) of 148 minutes (37–259 minutes) (P = .003), without prolonging sensory/motor blockade. Dexmedetomidine increased rates of hypotension (risk ratio [95% CI], 6.3 [1.5–27.5]; P = .01) and sedation (risk ratio [95% CI], 15.8 [3.9–64.6]; P = .0001). Overall risk of bias was moderate, and publication bias was noted, resulting in downgrading evidence strength. CONCLUSIONS: There is low-quality evidence that both adjuncts similarly prolong sensory/motor blockade. However, dexamethasone may be a superior adjunct; it improves the duration of analgesia by a statistically significant increase, albeit clinically modest, equivalent to 2.5 hours more than dexmedetomidine, without the risks of hypotension or sedation. Future direct comparisons are encouraged. Accepted for publication September 10, 2018. Funding: This work was supported by departmental funding from the Department of Anesthesia, Lausanne University Hospital, Lausanne, Switzerland (E.A.), and also from the Department of Anaesthesiology and Pain Medicine, and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (F.W.A.). Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Faraj W. Abdallah, MD, Department of Anesthesiology and Pain Medicine, and Ottawa Hospital Research Institute, University of Ottawa, The Ottawa Hospital General Campus, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. Address e-mail to FAbdallah@toh.ca. © 2018 International Anesthesia Research Society

https://ift.tt/2A415jz

Airway Management and Clinical Outcomes in External Laryngeal Trauma: A Case Series

External laryngeal trauma is a rare but potentially fatal event that presents several management challenges. This retrospective observational case series conducted at a level-1 trauma center over a 12-year period consists of 62 cases of acute external laryngeal trauma. Patient demographics, mode and mechanisms of injury, presenting signs and symptoms, initial imaging results, airway management, time to surgical management, and 6-month outcomes including airway status, deglutition status, and voice quality were investigated. No difference was found in mortality or 6-month outcomes between patients requiring surgical repair and/or tracheostomy versus patients with less severe injuries managed conservatively. Accepted for publication August 30, 2018. Funding: None. The authors declare no conflicts of interest. Institutional review board Number and Contact Information: HUM00125057. 2800 Plymouth Rd, Bldg 520, Room 3214, Ann Arbor, MI 48109. E-mail: irbmed@umich.edu. Reprints will not be available from the authors. Address correspondence to Alexandra R. DePorre, MD, Department of Anesthesiology, Michigan Medicine, University of Michigan, 1H247 UH, 1500 E Medical Center Dr, Ann Arbor, MI 48109. Address e-mail to adeporre@med.umich.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2QGXCgw

Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis

BACKGROUND: Propofol can cause degeneration of developing brain cells and subsequent long-term learning or memory impairment. However, at the early stage of embryonic development, the molecular mechanism of propofol-induced inhibition in neural stem cells (NSCs) neurogenesis is still unclear. The aim of this study was to determine the role of propofol in NSCs neurogenesis and, more importantly, to explore the underlying mechanism. METHODS: First, a single intraperitoneal injection of propofol was performed in pregnant mice, and 6 hours after administration of propofol, the hippocampus RNA and the protein of the embryos' brains was extracted to analyze the expression of neuron-specific markers. Second, the primary NSCs were isolated from the hippocampus of mouse embryonic brain and then treated with propofol for cell viability, immunostaining, and transwell assays; more importantly, we performed RNA sequencing (RNA-seq) and q-reverse transcription polymerase chain reaction assays to identify genes regulated by propofol; the Western blot, small interfering RNA (SiRNA), and luciferase reporter assays were used to study the effects of propofol on calmodulin-dependent protein kinase (CaMk) II/5' adenosine monophosphate-activated protein kinase (AMPK)/activating transcription factor 5 (ATF5) signaling pathway. RESULTS: Our results indicated that propofol treatment could inhibit the proliferation, migration, and differentiation of NSCs. The results of RNA-seq assays showed that propofol treatment resulted in downregulation of a group of Ca2+-dependent genes. The following mechanism studies showed that propofol regulates the proliferation, differentiation, and migration of NSCs through the CaMkII/phosphorylation of serine at amino acid position 485 (pS485)/AMPK/ATF5 signaling pathway. CONCLUSIONS: The results from study demonstrated that propofol inhibits the proliferation, differentiation, and migration of NSCs, and these effects are partially mediated by CaMkII/pS485/AMPK/ATF5 signaling pathway. Accepted for publication August 30, 2018. Funding: This research was supported by National Natural Science Foundation of China (Grant No. 81400930). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Jing Cang, MD, Department of Anesthesiology, Zhongshan Hospital, Fudan University, Xuhui Qu, Shanghai Shi 200032, China. Address e-mail to cangjing1998@126.com. © 2018 International Anesthesia Research Society

https://ift.tt/2QNA9dF

Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%–40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed. Accepted for publication August 27, 2018. Funding: This workshop was sponsored by the American Society of Anesthesiology Brain Health Initiative, the Society for Neuroscience in Anesthesiology and Critical Care, Baxter, and Pfizer. M.B. acknowledges receiving private consulting income from a legal case regarding postoperative cognitive function in an older adult and material support (ie, monitors) from Masimo for a research study. C.H.B. has consulted for and has a data share agreement with Medtronic. M.B. acknowledges support from National Institute on Aging (NIA) K76 AG057020 (and additional support from R03-AG050918 and P30AG028716), K.J.S. from National Institutes of Health (NIH) K12 HD043488 and an Alzheimer's Association Clinician Scientist Fellowship, C.H.B. from NIA K76 AG057020, S.G.D. from NIA K23 AG048332 and the American Foundation for Aging Research, R.A.W. from NIH 2R01GM101698, and R.G.E. from National Institute of General Medical Sciences P01 55876. All collaborators participated in the Best Practices Discussion at the 2016 International Perioperative Neurotoxicity Working Group meeting and helped edit the manuscript. The 2016 Perioperative Neurotoxicity Working group are also listed in Appendix. The authors declare no conflicts of interest. Address correspondence to Miles Berger, MD, PhD, Anesthesiology Department, Duke University Medical Center, 4317 Duke S Orange Zone, Durham, NC 27710. Address e-mail to Miles.berger@duke.edu. © 2018 International Anesthesia Research Society

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Effect of Apneic Oxygenation on Tracheal Oxygen Levels, Tracheal Pressure, and Carbon Dioxide Accumulation: A Randomized, Controlled Trial of Buccal Oxygen Administration

BACKGROUND: Apneic oxygenation via the oral route using a buccal device extends the safe apnea time in most but not all obese patients. Apneic oxygenation techniques are most effective when tracheal oxygen concentrations are maintained >90%. It remains unclear whether buccal oxygen administration consistently achieves this goal and whether significant risks of hypercarbia or barotrauma exist. METHODS: We conducted a randomized trial of buccal or sham oxygenation in healthy, nonobese patients (n = 20), using prolonged laryngoscopy to maintain apnea with a patent airway until arterial oxygen saturation (SpO2) dropped 90% during apnea. RESULTS: Buccal patients were more likely to achieve the primary outcome (P 94%; 750 seconds (750–750 seconds) vs 447 seconds (405–525 seconds); P

https://ift.tt/2A3CVpk

Preclinical Evaluation of Ropivacaine in 2 Liposomal Modified Systems

BACKGROUND: Our research group has recently developed liposomes with ionic gradient and in a combined manner as donor and acceptor vesicles containing ropivacaine (RVC; at 2% or 0.75%). Looking for applications of such novel formulations for postoperative pain control, we evaluated the duration of anesthesia, pharmacokinetics, and tissue reaction evoked by these new RVC formulations. METHODS: The formulations used in this study were large multivesicular vesicle (LMVV) containing sodium acetate buffer at pH 5.5 or in a combined manner with LMVV as donor and large unilamellar vesicles (LUVs) as acceptor vesicles with an external pH of 7.4. Wistar rats were divided into 6 groups (n = 6) and received sciatic nerve block (0.4 mL) with 6 formulations of RVC (LMVVRVC0.75%, LMVV/LUVRVC0.75%, LMVVRVC2%, LMVV/LUVRVC2%, RVC 0.75%, and RVC 2%). To verify the anesthetic effect, the animals were submitted to the pain pressure test and the motor block was also monitored. Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. Rats (n = 6) were submitted to a hind paw incision, and mechanical hypersensitivity was measured via the withdrawal response using von Frey filaments after injection of the 6 formulations. Finally, New Zealand white rabbits (n = 6) received sciatic nerve block (3 mL) with 1 of the 6 formulations of RVC. Blood samples were collected predose (0 minutes) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480, and 540 minutes after injection. RVC plasma levels were determined using a triple-stage quadrupole mass spectrometer. RESULTS: Duration and intensity of the sensory block were longer with all liposomal formulations, when compared to the plain RVC solution (P

https://ift.tt/2QGK3gR

Uncommon Imaging Findings of Inflammatory Myofibroblastic Tumor: Report of a Rare Case With Both Omentum and Mesentery Involvement in the Abdominal Cavity

The inflammatory myofibroblastic tumor (IMT) is a rare stromal tumor with diverse imaging findings. The present study describes a case of contrast-enhanced CT and 18F-FDG PET/CT manifestations of an IMT with diffuse omental and mesenteric thickening and swelling in the entire abdominal cavity. It is extremely rare to observe such imaging features in the extrapulmonary IMT. Furthermore, this case emphasizes that 18F-FDG PET/CT holds the potential for demonstrating IMT lesion extent and correctly identifying appropriate sites for biopsy.

https://ift.tt/2C7PPEd

A Case of Liver Injury Mimicking Metastasis After Gamma Knife Therapy for Lung Cancer: Evaluating by 18F-FDG PET/CT

A 52-year-old man presented a mixed low-density lesion with high FDG uptake in hepatic segment VIII after gamma knife therapy for lung cancer, which was easily misdiagnosed as hepatic metastasis. Follow-up PET/CT assessment demonstrated that the hepatic lesion was barely observed and without FDG accumulation 5 months after radiotherapy. This case suggests that a new FDG-avid lesion at PET/CT after radiotherapy for lung cancer can be caused by radiation-induced liver injury. Knowledge of its imaging characteristics and nature course evaluated by follow-up PET/CT is critical to avoid misinterpretation of this lesion as metastases.

https://ift.tt/2CCW1Fy

Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer

Purpose The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUVmax (nSUVmax). Materials and Methods A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUVmax measurements were normalized to the SUV of the pelvic blood pool. Patient, tumor, and PET/CT data were correlated to extracervical recurrence-free survival (ecRFS) and lymph node pathology. Results Of 113 patients, there were 23 (20%) extracervical recurrences. On univariate analysis, stage, histology, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node were significantly associated with ecRFS. On multivariable analysis, nSUVmax and radiographic size of the primary tumor remained associated with ecRFS (both P

https://ift.tt/2C8SAVQ

Huge Abdominal Photopenic Area Due to Kidney Cyst Imaged by Bone Scintigraphy in a Prostate Cancer Patient

Bone scintigraphy is a method of choice in evaluating metastatic disease in patients with prostatic cancer. We describe the case of a 77-year-old man who was subjected to bone scan for evaluation of secondary metastatic disease due to an elevated prostatic-specific antigen level (7.2). Bone scintigraphy demonstrated a huge photopenic area in the left upper abdominal area, as a result of a huge kidney cyst (15 × 13 cm).

https://ift.tt/2CCneZ0

68Ga PET Imaging in Patients With Neuroendocrine Tumors: A Systematic Review and Meta-analysis

Purpose The aim of this study was to systematically review the literature to assess the role of 68Ga PET imaging in neuroendocrine tumors (NETs). Materials and Methods The literature was searched using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases through OVID. Studies comparing PET or PET/CT with conventional imaging in the initial diagnosis, staging and restaging, assessment of treatment response, and routine surveillance of NETs were deemed eligible for inclusion. Risk of bias and applicability concerns were assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Results Twenty-two studies met the inclusion criteria. For the initial diagnosis of NETs, PET or PET/CT had a pooled sensitivity of 91% (95% confidence interval [CI], 85%–94%) and a pooled specificity of 94% (95% CI, 86%–98%). In the setting of staging and restaging, the sensitivity of PET or PET/CT for detecting primary and/or metastatic lesions ranged from 78.3% to 100%, whereas specificity ranged from 83% to 100%. Change in management occurred in 45% (95% CI, 36%–55%) of the cases, with majority of the changes involving surgical planning and patient selection for peptide receptor radionuclide therapy. Conclusions 68Ga PET or PET/CT is recommended for initial diagnosis where conventional testing remained equivocal, for staging of patients with localized primary and/or limited metastasis where definitive surgery is planned, to determine somatostatin receptor status and suitability for peptide receptor radionuclide therapy, and for staging of patients where detection of occult disease will alter treatment options and decision making.

https://ift.tt/2C8SxJE

Imaging Brain Metastasis Patients With 18F-(2S,4R)-4-Fluoroglutamine

Purpose There is a need for an alternative PET probe, which does not show normal brain tissue uptake in the evaluation of metastasis to the brain. Therefore, we investigate the feasibility of 18F-labeled glutamine analog, 18F-(2S,4R)-4-fluoroglutamine (18F-FGln), as a new metabolic probe to detect brain metastasis. Methods Patients (7 men and 7 women; age, 25–67 years) with suspected brain metastasis were enrolled for this study. All patients were imaged first with 18F-FGln PET (3 patients for 1-hour dynamic whole-body PET/CT scans, and 11 patients for static whole-body scans at 30 ± 10 minutes after injection), followed by a whole-body 18F-FDG PET performed in the same week. The characteristics of 18F-FGln PET imaging in brain metastasis patients were compared with that of 18F-FDG PET and/or contrast-enhanced MRI patient-by-patient. A composite of all functional and anatomic imaging studies served as the imaging comparator. Results Initial study in 3 patients using 1-hour dynamic scan showed that 30 ± 10 minutes after injection is optimal for identifying brain metastasis with a high-contrast ratio. All patients were positive for brain metastasis on this studies that demonstrated 38 lesions in 6 anatomic regions on the imaging comparator. The per-lesion detection rates for 18F-FGln PET and 18F-FDG PET were 81.6% and 36.8%, respectively. The average tumor-to-normal brain ratio of 18F-FGln PET was significantly better than that of 18F-FDG PET in all patients (4.97 ± 2.23 vs 1.22 ± 0.69, P

https://ift.tt/2CGsxqa

SUV Harmonization Between Different Hybrid PET/CT Systems

Aim Current PET/CT lutetium oxyorthosilicate (LSO) or lutetium-yttrium oxyorthosilicate crystal scanners are equipped with sophisticated softwares including point-spread function (PSF) and time-of-flight (TOF) image reconstruction. These softwares are associated with increased SUVs compared with 3D-OSEM reconstructions associated with older BGO PET/CT scanners. The European Association of Nuclear Medicine (EANM) identified the problem of SUV harmonization since 2010 through the EANM Research Ltd European Association of Nuclear Medicine Research Ltd [EARL] FDG PET/CT accreditation program. This required processing 2 reconstructions, one optimized for maximum spatial lesion detection and one for harmonized quantitation. We investigated an alternative single reconstruction method for both qualitative and quantitative analysis optimized to maximize spatial lesion detectability, followed by an intrinsic postreconstruction algorithm for SUV harmonization. Methods Phantom and "in vivo" patient data analysis were acquired and analyzed on (a) a Siemens Biograph mCT system with LSO crystals and PSF and TOF algorithms, and on (b) a General Electric Discovery STE system with BGO crystals, without PSF and TOF. A dedicated algorithm (EQ.filter) was tested to harmonize SUV between the 2 scanners compared with EANM/EARL specifications. NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small fillable spheres (lesion to background ratios of 8:1 and 4:1) were used. Phantom data were validated on 7 oncologic patients with 39 hyperactive lesions ranging from 3 mm to 26 mm. Results The main benefit of PSF + TOF LSO PET/CT systems was increased contrast for small active lesions. Recovery coefficients measured according to NEMA standards exceeded those obtained by 3D-OSEM reconstruction. SUVmax discrepancies between the 2 PET/CT systems were as high as 149%, dropping to below 10% when optimized by EQ.filter. Conclusions A single reconstruction optimized by EQ.filter for maximum spatial lesion detectability is an easy and precise solution to harmonize SUVs between different PET/CT scanners, avoiding a second reconstruction with an additional smoothing filter as requested by EANM/EARL.

https://ift.tt/2C9tQNl

Cervical Cancer Presenting as an Omental Cake

In women, peritoneal carcinomatosis usually originates from primary ovarian cancer. We report a case of omental cake as the initial presentation of a cervical cancer, which is extremely rare for this disease. 18F-FDG PET/CT imaging demonstrated diffuse hypermetabolic abdominopelvic peritoneal carcinomatosis originating from cervical cancer that was confirmed by histopathologically.

https://ift.tt/2CCkV7Y

Quality and Safety in Health Care, Part XLI: The IMPACT Registry

The IMPACT Registry is a repository of information for heart catheterizations for congenital heart disease regardless of age and also the catheterizations for acquired heart disease in children. The registry collects information on outcomes, provides quality improvement opportunities for participants, provides reports to participants comparing their results with national results, compares the volume of catheter work done at an institution with the frequency of adverse events, and provides information that may be helpful in evaluating the use of medical devices and treatment options.

https://ift.tt/2Cbij06

Re: Response Assessment of 223Ra Treatment Should a Fluorocholine PET/CT Be Performed?

No abstract available

https://ift.tt/2CBqmnO

99mTc Sodium Pertechnetate Uptake in Ectopic Mediastinal Thyroid Tissue on Hybrid Thyroid Scintigraphy

Ectopic thyroid is a rare/incidental imaging finding. When discovered, 90% of ectopic thyroid is found typically along the pathway of embryologic migration of thyroid tissue, whereas around 10% have been discovered in other anatomical locations including the mediastinum and the heart. Thyroid scintigraphy with 99mTc sodium pertechnetate (TcO4) is peculiar for thyroid tissue uptake. The current case, clinically euthyroid, had heterogeneous uptake in multinodular goiter with uptake in the ectopic thyroid tissue in right paratracheal location on functional imaging with TcO4. Subsequent single photon emission computed tomography/computed tomography (SPECT/CT) imaging confirmed the ectopic thyroid tissue.

https://ift.tt/2Cb51kf

Oropharyngeal Squamous Cell Carcinoma Metastasis to Distal Skeletal Muscle on FDG PET/CT

We present a case of a tongue squamous cell carcinoma (SCC) metastasizing to distal skeletal muscle detected on FDG PET/CT imaging. A 48-year-old man with locally recurrent tongue SCC underwent a restaging FDG PET/CT to investigate neck and unilateral leg pain. The PET scan showed large, intensely FDG-avid lesions in the right scalene and left hamstring muscles, which were biopsy proven as metastatic SCC. Skeletal muscle metastases from oropharyngeal SCCs are rare; however, PET/CT has allowed increased detection of atypical metastatic sites. Such cases support the consideration of metastasis for muscular lesions in head and neck cancer patients.

https://ift.tt/2CCkVF0

Bile Collection Detected With BrIDA Scintigraphy in a Patient With Hepatocellular Carcinoma

A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently, hospitalization was required because of high fever (up to 39°C), weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of the intrahepatic fluid collections. Biochemical and microbiological analyses of a fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus and Enterobacter cloacae. Thus, the patient underwent 99mTc-trimethylbromo-iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with a flow from a bile duct.

https://ift.tt/2C6N5ai

99mTc-MDP Bone Scan and 18F-FDG PET/CT Imaging of Multiple Extraskeletal Osteosarcomas

Extraskeletal osteosarcomas are uncommon entities in clinical practice, which account for 1% to 2% of all soft tissue sarcomas. We here reported a case of multiple extraskeletal osteosarcomas and nuclear medicine imaging findings of this disease in 99mTc-MDP bone scan as well as 18F-FDG PET/CT.

https://ift.tt/2CAZ4xL

The Coexistence of a Horseshoe Kidney and Meckel Diverticulum With Dramatic Mobility Revealed Through 99mTc Pertechnetate Imaging

A previously healthy 11-year-old boy with intermittent abdominal pain and bloody stool underwent Meckel scintigraphy. On the initial images, there was a faint U-shaped activity in the mid-abdominal region, which gradually faded and evolved into distinct foci of radiotracer accumulation in the later images. One of the foci changed its location during the study, suspected as moving Meckel diverticulum. A horseshoe kidney was noted by subsequent CT images, which corresponded to nonmoving foci. A Meckel diverticulum was confirmed after exploratory laparotomy, accounted for moving focus on Merkel scintigraphy.

https://ift.tt/2CcrEEy

The Pattern of Striatal Dopamine Depletion as a Prognostic Marker in De Novo Parkinson Disease

Purpose To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD). Methods Approximately 634 patients with drug-naive PD who underwent 18F-FP-CIT PET scans were followed up for at least 2 years. After quantifying dopamine transporter (DAT) availability in each striatal subregion, the patterns of striatal dopamine depletion of each patient were assessed based on (1) the degree of dopamine loss in the other striatal subregions compared to the posterior putamen (inter-subregional ratio [ISR]) and (2) the interhemispheric asymmetry of dopamine loss in the posterior putamen (asymmetry index [AI]). According to their patterns, we assessed the longitudinal changes in L-dopa-equivalent doses and L-dopa-induced dyskinesia (LID)-free times using the linear mixed model and Cox regression model, respectively. Results There was no significant correlation between the ISR and AI values (Pearson correlation coefficient, 0.150). The linear mixed model showed that higher AI values were associated with slower longitudinal increases in L-dopa-equivalent dose across time (P = 0.003), whereas ISR values were not (P = 0.154). The Cox regression model demonstrated that higher ISR values were associated with early development of LID (hazard ratio, 1.693; P = 0.010), whereas AI values were not (P = 0.269). Conclusions The present study demonstrated that the pattern of anterior-to-posterior gradient and right-to-left asymmetry of striatal DAT availability predicted the development of LID and increasing doses of dopaminergic medications.

https://ift.tt/2CB0VCR

FDG PET/CT Findings in TAFRO Syndrome

A 67-year-old woman with prolonged fever, thrombocytopenia, and renal dysfunction underwent FDG PET/CT to evaluate underlying causes, including malignancy. PET/CT showed FDG uptake in ascites, subcutaneous edema, lymph nodes, spleen, and bone marrow. Subsequent bone marrow biopsy revealed myelofibrosis, and laboratory testing showed elevated concentrations of interleukin 6 in serum and ascites. These findings led to the diagnosis of TAFRO syndrome, a variant of multicentric Castleman disease, characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, and organomegaly. Because TAFRO syndrome is potentially fatal, accurate diagnosis is crucial. Characteristic FDG PET/CT findings facilitate the diagnosis of TAFRO syndrome, which is generally challenging.

https://ift.tt/2C8v8be

Congenital Penile Rhabdomyosarcoma on FDG PET/CT

Primary penile malignancy is uncommon. Congenital primary penile rhabdomyosarcoma diagnosed in an infant is extremely rare. We present the FDG PET/CT findings in a 1-month-old boy with penile mass. The images showed hypermetabolic lesion at the base of the penis and left inguinal lymph node. Pathological examination demonstrated rhabdomyosarcoma.

https://ift.tt/2CBWVll

New era of robotic surgical systems

Asian Journal of Endoscopic Surgery, EarlyView.


https://ift.tt/2IN7d2j

Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti‐viral therapy in patients with chronic hepatitis B

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2pMkorC

A Highly Porous Copper Electrocatalyst for Carbon Dioxide Reduction

Advanced Materials, EarlyView.


https://ift.tt/2pJnWLs

“Genetically Engineered” Biofunctional Triboelectric Nanogenerators Using Recombinant Spider Silk

Advanced Materials, EarlyView.


https://ift.tt/2IQ3p0z

Triangulating abuse liability assessment for flavoured cigar products using physiological, behavioural economic and subjective assessments: a within-subjects clinical laboratory protocol

Introduction

In the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability.

Methods and analyses

Participants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18–25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models.

Ethics and dissemination

The Virginia Commonwealth University Institutional Review Board approved the study (VCU IRB: HM20007848). Dissemination channels for study findings include scientific journals, scientific meetings, and policy briefs.

Trial registration number

NCT02937051.

https://ift.tt/2C6HC3g

Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (The GerMoT study)

Introduction

Comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary diagnostic process used to determine the medical, psychological and functional capabilities of frail older people. The primary aim of our current study is to confirm whether CGA-based outpatient care is superior than usual care in terms of health-related outcomes, resource use and costs.

Methods and analysis

The Geriatric Mobile Team trial is designed as a single-centre randomised, controlled, assessor-blinded (at baseline) trial. All participants will be identified via local healthcare registries with the following inclusion criteria: age ≥75 years, ≥3 different diagnoses and ≥3 visits to the emergency care unit (with or without admittance to hospital) during the past 18 months. Nursing home residency will be an exclusion criterion. Baseline assessments will be done before the 1:1 randomisation. Participants in the intervention group will, after an initial CGA, have access to care given by a geriatric team in addition to usual care. The control group receives usual care only. The primary outcome is the total number of inpatient days during the follow-up period. Assessments of the outcomes: mortality, quality of life, health care use, physical functional level, frailty, dependence and cognition will be performed 12 and 24 months after inclusion. Both descriptive and analytical statistics will be used, in order to compare groups and for analyses of outcomes over time including changes therein. The primary outcome will be analysed using analysis of variance, including in-transformed values if needed to achieve normal distribution of the residuals.

Ethics and dissemination

Ethical approval has been obtained and the results will be disseminated in national and international journals and to health care leaders and stakeholders. Protocol amendments will be published in ClinicalTrials.gov as amendments to the initial registration NCT02923843. In case of success, the study will promote the implementation of CGA in outpatient care settings and thereby contribute to an improved care of older people with multimorbidity through dissemination of the results through scientific articles, information to politicians and to the public.

Trial registration number

NCT02923843; Pre-results.

https://ift.tt/2C8IC6P

Making sense of recovery after traumatic brain injury through a peer mentoring intervention: a qualitative exploration

Objective

To explore the acceptability of peer mentoring for people with a traumatic brain injury (TBI) in New Zealand.

Design

This is a qualitative descriptive study exploring the experiences reported by mentees and mentors taking part in a feasibility study of peer mentoring. Interviews with five mentees and six mentors were carried out. Data were analysed using conventional content analysis.

Setting

The first mentoring session took place predischarge from the rehabilitation unit. The remaining five sessions took place in mentees' homes or community as preferred.

Participants

Twelve people with TBI took part: six mentees (with moderate to severe TBI; aged 18–46) paired with six mentors (moderate to severe TBI >12 months previously; aged 21–59). Pairing occurred before mentee discharge from postacute inpatient brain injury rehabilitation. Mentors had been discharged from rehabilitation following a TBI between 1 and 5 years previously.

Intervention

The peer mentoring programme consisted of up to six face-to-face sessions between a mentee and a mentor over a 6-month period. The sessions focused on building rapport, exploring hopes for and supporting participation after discharge through further meetings and supported community activities.

Results

Data were synthesised into one overarching theme: making sense of recovery. This occurred through the sharing of experiences and stories; was pivotal to the mentoring relationship; and appeared to benefit both mentees and mentors. Mentors were perceived as valued experts because of their personal experience of injury and recovery, and could provide support in ways that were different from that provided by clinicians or family members. Mentors required support to manage the uncertainties inherent in the role.

Conclusions

The insight mentors developed through their own lived experience established them as a trusted and credible source of hope and support for people re-engaging in the community post-TBI. These findings indicate the potential for mentoring to result in positive outcomes.

https://ift.tt/2CGfa9s

Detection and treatment initiation for depression and alcohol use disorders: facility-based cross-sectional studies in five low-income and middle-income country districts

Objectives

To estimate the proportion of adult primary care outpatients who are clinically detected and initiate treatment for depression and alcohol use disorder (AUD) in low-income and middle-income country (LMIC) settings.

Design

Five cross-sectional studies.

Setting

Adult outpatient services in 36 primary healthcare facilities in Sodo District, Ethiopia (9 facilities); Sehore District, India (3); Chitwan District, Nepal (8); Dr Kenneth Kaunda District, South Africa (3); and Kamuli District, Uganda (13).

Participants

Between 760 and 1893 adults were screened in each district. Across five districts, between 4.2% and 20.1% screened positive for depression and between 1.2% and 16.4% screened positive for AUD. 96% of screen-positive participants provided details about their clinical consultations that day.

Primary outcomes

Detection of depression, treatment initiation for depression, detection of AUD and treatment initiation for AUD.

Results

Among depression screen-positive participants, clinical detection of depression ranged from 0% in India to 11.7% in Nepal. Small proportions of screen-positive participants received treatment (0% in Ethiopia, India and South Africa to 4.2% in Uganda). Among AUD screen-positive participants, clinical detection of AUD ranged from 0% in Ethiopia and India to 7.8% in Nepal. Treatment was 0% in all countries aside Nepal, where it was 2.2%.

Conclusions

The findings of this study suggest large detection and treatment gaps for adult primary care patients, which are likely contributors to the population-level mental health treatment gap in LMIC. Primary care facilities remain unfulfilled intervention points for reducing the population-level burden of disease in LMIC.

https://ift.tt/2C6WBdA

Young age at school entry and attention-deficit hyperactivity disorder-related symptoms during primary school: results of a prospective cohort study conducted at German Rudolf Steiner Schools

Objectives

Young age at school entry (ASE) for students has been related to their impaired mental health in higher grades. To avoid the negative health consequences of young ASE, preschool examinations and individual school entry deferral for young children are routinely performed by some school authorities. We aimed to investigate whether ASE was associated with attention-deficit hyperactivity disorder (ADHD)-related symptoms in pupils attending schools using a selective school enrolment procedure.

Design

Prospective open cohort study with baseline assessments at school entry and two follow-ups in the second and fourth grades.

Setting

Up to 128 Rudolf Steiner Schools (Waldorf Schools) located within Germany.

Participants

Of the 3079 children from whom data were gathered in the second or fourth grade, 2671 children born between 1 July 2001 and 31 October 2002 (age at baseline: mean 6.7, min 5.91, max 7.24 years, 50% girls) were selected for analysis to avoid bias introduced by individuals at the edges of the ASE distribution.

Main outcome measures

ADHD-related symptoms were assessed at school entry and second and fourth grades by parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire (Hyperactivity-Inattention Subscale).

Results

The agreement between parent-reported and teacher-reported symptoms was poor (intra-class correlation: 0.41 and 0.44 in second and fourth grade assessments, respectively). Regarding teacher reports, ASE was negatively associated with ADHD-related symptoms in the second grade (regression coefficient β=–0.66 per year, P=0.0006) and fourth grade (β=–0.56, P=0.0014). Associations remained after adjusting for potential confounders and pre-existing symptoms at baseline. Regarding parent reports, associations were markedly weaker in both grades (second grade: β=–0.22, P=0.12; fourth grade: β=–0.09, P=0.48).

Conclusions

Using a prospective study design and comprehensive adjustment for confounding and baseline symptoms, we confirmed prior evidence of the association between young ASE and teacher-reported ADHD symptoms in primary school.

https://ift.tt/2CGeP6G

Burden of seasonal influenza in sub-Saharan Africa: a systematic review protocol

Introduction

Measures of epidemiological burdens are an important contribution to estimating disease severity and determining the at-risk populations for seasonal influenza. In the absence of these data, it is extremely difficult for policy-makers to decide on how to distribute limited resources. This systematic review will synthesise the literature on reported burden of seasonal influenza (eg, morbidity and mortality) in sub-Saharan Africa.

Method and analysis

We will include published epidemiological studies that capture the burden estimation of seasonal influenza between 1 January 2000 and 31 August 2018. Studies that have reported disease burden estimates associated to influenza-like illness, acute respiratory illness, acute lower respiratory illness, severe acute respiratory illness and severe or very severe pneumonia using laboratory-confirmed influenza cases will be included. We will perform a multiple electronic database search in PubMed, Embase, African Journals Online, Cochrane, Web of science, CINAHL and Google scholar for eligible studies. The reference lists of relevant studies will also be hand-searched for potentially eligible studies. The titles and abstracts of identified records will be screened independently by two authors. The full-text articles of potentially eligible studies will be assessed independently by two authors. Discrepancies will be resolved by discussion, and by a third author if the first two authors fail to come to a consensus. The measures of the burden of influenza will be aggregated using a meta-analysis for homogeneous studies and narrative synthesis if the studies are heterogeneous. The strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

This systematic review will use publicly available data; and as such, no formal ethical review is required. Our findings will be published in a peer-reviewed journal and also disseminated through conferences and stakeholder meetings.

PROSPERO registration number

CRD42017074091.

https://ift.tt/2C8I6Wr

Cohort Study of Pulmonary Tuberculosis (COSMOTB) identifying drug-resistant mutations: protocol for a prospective observational study in Korea

Introduction

Drug-resistant tuberculosis (TB) is a global concern. The proper diagnosis and management of drug-resistant TB are critical for improving treatment outcome. Molecular-based genotypic drug-susceptibility testing (DST) was developed to identify drug-resistant TB; however, discordant results from phenotypic and genotypic DST analyses have alarmed clinicians and raised concerns about the test's utility. Moreover, the characteristics of disputed mutations are not well studied and only based on retrospective study findings.

Methods and analysis

We describe a 28-month prospective observational cohort study ongoing at two university-affiliated hospitals in South Korea. The cohort study will enrol and evaluate 600 adults with pulmonary TB. Relevant clinical and epidemiological data will be collected prospectively and participants will be evaluated at each hospital during anti-TB treatment to identify factors associated with TB treatment outcomes. Respiratory specimens will be collected at select visits. After generating a well-characterised cohort, patterns of drug resistance on both phenotypic and genotypic DSTs and associated mutations including the disputed mutation will be evaluated. We will also identify various clinical and socioeconomic factors that affect the causes of drug resistance and their clinical outcomes.

Ethics and dissemination

The study protocol is approved by the Institutional Review Boards of Chungbuk National University Hospital and Chungnam National University Hospital. Study results will be disseminated through peer-reviewed journals and conference presentations.

Trial registration number

KCT0002594.

https://ift.tt/2CDjqXh

Initial treatment of steroid-sensitive idiopathic nephrotic syndrome in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial (INTENT study)

Introduction

Idiopathic nephrotic syndrome is the most common glomerular disease in childhood with an incidence of 1.8 cases per 100 000 children in Germany. The treatment of the first episode implies two aspects: induction of remission and sustainment of remission. The recent Kidney Disease Improving Global Outcomes, American Academy of Pediatrics and German guidelines for the initial treatment of the first episode of a nephrotic syndrome recommend a 12-week course of prednisone. Despite being effective, this treatment is associated with pronounced glucocorticoid-associated toxicity due to high-dose prednisone administration over a prolonged period of time. The aim of the INTENT study (Initial treatment of steroid-sensitive idiopathic nephrotic syndrom in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial) is to show that an alternative treatment regimen with mycophenolic acid is not inferior regarding sustainment of remission, but with lower toxicity compared with treatment with glucocorticoids only.

Methods and design

The study is designed as an open, randomised, controlled, multicentre trial. 340 children with a first episode of steroid-sensitive nephrotic syndrome and who achieved remission by a standard prednisone regimen will be enrolled in the trial and randomised to one of two treatment arms. The standard care group will be treated with prednisone for a total of 12 weeks; in the experimental group the treatment is switched to mycophenolate mofetil, also for a total of 12 weeks in treatment duration. The primary endpoint is the occurrence of a treated relapse within 24 months after completion of initial treatment.

Ethics and dissemination

Ethics approval for this trial was granted by the ethics committee of the Medical Faculty of the University of Heidelberg (AFmu-554/2014). The study results will be published in accordance with the Consolidated Standards of Reporting Trials statement and the Standard Protocol Items: Recommendations for Interventional Trials guidelines. Our findings will be submitted to major international paediatric nephrology and general paediatric conferences and submitted for publication in a peer-reviewed, open-access journal.

Trial registration number

DRKS0006547; EudraCT2014-001991-76; Pre-result.

Date of registration

30 October 2014; 24 February 2017.

https://ift.tt/2CAPyuF

Is establishing a specialist back pain assessment and management service in primary care a safe and effective model? Twelve-month results from the Back pain Assessment Clinic (BAC) prospective cohort pilot study

Objectives

To report on the design, implementation and evaluation of the safety and effectiveness of the Back pain Assessment Clinic (BAC) model.

Design

BAC is a new, community-based specialist service for assessing and managing neck and low back pain (LBP). The BAC pilot was supported by a Victorian Department of Health and Human Services grant and was evaluated using the Victorian Innovation Reform Impact Assessment Framework (VIRIAF). Data were obtained by auditing BAC activity (22 July 2014 to 30 June 2015) and conducting surveys and interviews of patients, stakeholders and referrers.

Setting

Tertiary and primary care.

Participants

Adult patients with neck and LBP referred for outpatient surgical consultation.

Main outcome measures

VIRIAF outcomes: (1) access to care; (2) appropriate and safe care; (3) workforce optimisation and integration; and (4) efficiency and sustainability.

Results

A total of 522 patients were seen during the pilot. Most were referred to hospital services by general practitioners (87%) for LBP (63%) and neck pain (24%). All patients were seen within 10 weeks of referral and commenced community-based allied health intervention within 2–4 weeks of assessment in BAC. Of patients seen, 34% had medications adjusted, 57% were referred for physiotherapy, 3.2% to pain services, 1.1% to rheumatology and 1.8% for surgical review. Less MRI scans were ordered in BAC (6.4%) compared with traditional spinal surgical clinics (89.8%), which translated to a cost-saving of $52 560 over 12 months. Patient and staff satisfaction was high. There have been no patient complaints or adverse incidents.

Conclusion

Evaluation of the BAC pilot suggests it is a potentially safe and cost-saving alternative model of care. Results of the BAC pilot merit further evaluation to determine the potential cost-effectiveness, longer term and broader societal impact of implementing BAC more widely.

https://ift.tt/2C8HPmn

Egg white hydrolysate improves fatigue due to short‐term swimming load test in mice

Food Science &Nutrition, EarlyView.


https://ift.tt/2yyPo2f

Aberrant MCT4 and GLUT1 expression is correlated with early recurrence and poor prognosis of hepatocellular carcinoma after hepatectomy

Cancer Medicine, EarlyView.


https://ift.tt/2PoUXI4

National Cancer Database Comparison of Radical Cystectomy vs Chemoradiotherapy for Muscle‐Invasive Bladder Cancer: Implications of Using Clinical vs Pathologic Staging

Cancer Medicine, EarlyView.


https://ift.tt/2ycbsRa

Modification of American Joint Committee on cancer prognostic groups for renal cell carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2PoUXb2

Strong impact of sulfotransferases on DNA adduct formation by 4‐aminobiphenyl in bladder and liver in mice

Cancer Medicine, EarlyView.


https://ift.tt/2yc3APw

Identification of a six‐gene signature with prognostic value for patients with endometrial carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2PssVve

Role of serum EBV‐VCA IgG detection in assessing gastric cancer risk and prognosis in Northern Chinese population

Cancer Medicine, EarlyView.


https://ift.tt/2ybGet9

Postoperative chemotherapy had no prognostic effect on early‐staged young ovarian cancer with unilateral resection

Cancer Medicine, EarlyView.


https://ift.tt/2Ogt0pg

n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis

Abstract

Epilepsy therapy is based on drugs that treat the symptoms rather than the underlying mechanisms of the disease (epileptogenesis). There are no treatments for preventing seizures or improving disease prognosis, including neurological comorbidities. The search of pathogenic mechanisms of epileptogenesis highlighted that neuroinflammatory cytokines [i.e. interleukin-1β (IL-1β), tumour necrosis factor-α (Tnf-α)] are induced in human and experimental epilepsies, and contribute to seizure generation in animal models. A major role in controlling the inflammatory response is played by specialized pro-resolving lipid mediators acting on specific G-protein coupled receptors. Of note, the role that these pathways have in epileptogenic tissue remains largely unexplored. Using a murine model of epilepsy, we show that specialized pro-resolving mechanisms are activated by status epilepticus before the onset of spontaneous seizures, but with a marked delay as compared to the neuroinflammatory response. This was assessed by measuring the time course of mRNA levels of 5-lipoxygenase (Alox5) and 15-lipoxygenase (Alox15), the key biosynthetic enzymes of pro-resolving lipid mediators, versus Il1b and Tnfa transcripts and proteins. In the same hippocampal tissue, we found a similar delayed expression of two main pro-resolving receptors, the lipoxin A₄ receptor/formyl peptide receptor 2 and the chemerin receptor. These receptors were also induced in the human hippocampus after status epilepticus and in patients with temporal lobe epilepsy. This evidence supports the hypothesis that the neuroinflammatory response is sustained by a failure to engage pro-resolving mechanisms during epileptogenesis. Lipidomic LC-MS/MS analysis showed that lipid mediator levels apt to resolve the neuroinflammatory response were also significantly altered in the hippocampus during epileptogenesis with a shift in the biosynthesis of several pro-resolving mediator families including the n-3 docosapentaenoic acid (DPA)-derived protectin D1. Of note, intracerebroventricular injection of this mediator during epileptogenesis in mice dose-dependently reduced the hippocampal expression of both Il1b and Tnfa mRNAs. This effect was associated with marked improvement in mouse weight recovery and rescue of cognitive deficit in the novel object recognition test. Notably, the frequency of spontaneous seizures was drastically reduced by 2-fold on average and the average seizure duration was shortened by 40% after treatment discontinuation. As a result, the total time spent in seizures was reduced by 3-fold in mice treated with n-3 DPA-derived protectin D1. Taken together, the present findings demonstrate that epilepsy is characterized by an inadequate engagement of resolution pathways. Boosting endogenous resolution responses significantly improved disease outcomes, providing novel treatment avenues.

https://ift.tt/2NCoJHw

Correction to: Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer

In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.

https://ift.tt/2EfqPOe

GLI2 promotes cell proliferation and migration through transcriptional activation of ARHGEF16 in human glioma cells

Abstract

Background

The Hedgehog (Hh) signaling pathway plays critical roles in modulating embryogenesis and maintaining tissue homeostasis, with glioma-associated oncogene (GLI) transcription factors being the main mediators. Aberrant activation of this pathway is associated with various human malignancies including glioblastoma, although the mechanistic details are not well understood.

Methods

We performed a microarray analysis of genes that are differentially expressed in glioblastoma U87 cells overexpressing GLI2A, the active form of GLI2, relative to the control cells. Chromatin immunoprecipitation and dual-luciferase assays were used to determine whether Rho guanine nucleotide exchange factor 16 (ARHGEF16) is a downstream target of GLI2. Then, transwell migration, EdU and soft-agar colony formation assays were employed to test effects of ARHGEF16 on glioma cancer cell migration and proliferation, and the effects of GLI2/ARHGEF16 signaling on tumor growth were examined in vivo. Finally, we performed yeast two-hybrid assay, Co-IP and GST-pull down to identify factors that mediate effects of ARHGEF16.

Results

We found that ARHGEF16 mRNA level was upregulated in U87 cells overexpressing GLI2A relative to control cells. GLI2 binds to the ARHGEF16 promoter and activates gene transcription. Glioma cells U87 and U118 overexpressing ARHGEF16 showed enhanced migration and proliferation relative to the control cells, while knockdown of ARHGEF16 in H4 cells led to decreased cell proliferation compared to the control H4 cells. In contrast to the promoting effect of GLI2A overexpression on glioma xenograft growth, both GLI2 inhibition and ARHGEF16 knockdown retarded tumor growth. Cytoskeleton-associated protein 5 (CKAP5) was identified as an interaction protein of ARHGEF16, which is important for the stimulatory effects of ARHGEF16 on glioma cell migration and proliferation.

Conclusions

These results suggest that therapeutic strategies targeting the GLI2/ARHGEF16/CKAP5 signaling axis could inhibit glioma progression and recurrence.

https://ift.tt/2yvSX9v

Mechanism of piR-DQ590027/MIR17HG regulating the permeability of glioma conditioned normal BBB

Abstract

Background

The blood-brain barrier (BBB) strongly restricts the entry of anti-glioma drugs into tumor tissues and thus decreases chemotherapy efficacy. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumor form. Because regulation of the effect of noncoding RNA on BBB function is attracting growing attention, we investigated the effects of noncoding RNA on the permeability of glioma conditioned normal BBB and the mechanism involved using PIWI-associated RNA piR-DQ590027 as a starting point.

Methods

The mRNA levels of MIR17HG, miR-153, miR-377, ZO-1, occludin, and claudin-5 were determined using real-time PCR. Transient cell transfection was performed using Lipofectamine 3000 reagent. TEER and HRP flux were applied to measure the permeability of glioma conditioned normal BBB. Western blotting and immunofluorescence assays were used to measure ZO-1, occludin, and claudin-5 levels. Reporter vector construction and a luciferase reporter assay were performed to detect the binding sites of MIR17HG and piR-DQ590027, MIR17HG and miR-153 (miR-377), and FOXR2 and miR-153 (miR-377). RNA immunoprecipitation was used to test the interaction between miR-153 (miR-377) and its target proteins. Chromatin immunoprecipitation was performed to detect the interaction between the transcription factor FOXR2 and ZO-1, occludin, and claudin-5.

Results

piR-DQ590027 was expressed at low levels in glioma-conditioned ECs (GECs) of the in vitro glioma conditioned normal BBB model. Overexpression of piR-DQ590027 down-regulated the expressions of ZO-1, occludin, and claudin-5 and increased the permeability of glioma conditioned normal BBB. MIR17HG had high expression in GECs but miR-153 and miR-377 had low expression. piR-DQ590027 bound to and negatively regulated MIR17HG. FOXR2 was a downstream target of miR-153 and miR-377; MIR17HG bound separately to miR-153 and miR-377 and negatively regulated their ability to mediate FOXR2 expression. FOXR2 associated with the promoter regions of ZO-1, occludin, and claudin-5 in GECs to promote their transcription.

Conclusion

The piR-DQ590027/MIR17HG/miR-153 (miR-377)/FOXR2 pathway plays an important role in regulating glioma conditioned normal BBB permeability and provides a new target for the comprehensive treatment of glioma.

https://ift.tt/2OktaMa

Hypersensitivity and infusion-site adverse events with intravenous fosaprepitant after anthracycline-containing chemotherapy: a retrospective study

Future Oncology, Ahead of Print.


https://ift.tt/2CD5fkX

Beyond BCG: the approaching era of personalised bladder-sparing therapies for non-muscle-invasive urothelial cancers

Future Oncology, Ahead of Print.


https://ift.tt/2C7tFC8

Corrigendum

Future Oncology, Ahead of Print.


https://ift.tt/2CAIQ7P

Monitoring excess unplanned return to theatre following colorectal cancer surgery

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2OXUdg9

Predicting post‐operative pancreatic fistulae using preoperative pancreatic imaging: a systematic review

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2NyC3ww

Topical haemostatic powder as a novel endoscopic therapy for severe colonic diverticular bleeding

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2OObFnc

Clinical value of preoperative CA19‐9 levels in evaluating resectability of gallbladder carcinoma

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2Nvr8nn

Obturator nerve ganglion cyst: masquerading as groin hernia

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2OP38jM

Aviation‐based teamwork skills work for surgeons: time for an ‘aviation bundle’?

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2NBv6L1

Compassion is a key quality for palliative care teams

Cancer Medicine, EarlyView.


https://ift.tt/2OPoFsI

Predictive value of pediatric respiratory-induced diaphragm motion quantified using pre-treatment 4DCT and CBCTs

Abstract

Background

In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have indicated that a 4D-CT is not always representative for respiratory motion. Our aim was to investigate whether respiratory-induced diaphragm motion in children on a single pre-treatment 4DCT can accurately predict respiratory-induced diaphragm motion as observed on cone beam CTs (CBCTs).

Methods

Twelve patients (mean age 14.5 yrs.; range 8.6–17.9 yrs) were retrospectively included based on visibility of the diaphragm on abdominal or thoracic imaging data acquired during free breathing. A 4DCT for planning purposes and daily/weekly CBCTs (total 125; range 4–29 per patient) acquired prior to dose delivery were available. The amplitude, corresponding to the difference in position of the diaphragm in cranial-caudal direction in end-inspiration and end-expiration phases, was extracted from the 4DCT (A_4DCT). The amplitude in CBCTs (A_CBCT) was defined as displacement between averaged in- and expiration diaphragm positions on corresponding projection images, and the distribution of A_CBCT was compared to A_4DCT (one-sample t-test, significance level p < 0.05).

Results

Over all patients, the mean A_4DCT was 10.4 mm and the mean A_CBCT 11.6 mm. For 9/12 patients, A_4DCT differed significantly (p < 0.05) from A_CBCT. Differences > 3 mm were found in 69/125 CBCTs (55%), with A_4DCT mostly underestimating A_CBCT. For 7/12 patients, diaphragm positions differed significantly from the baseline position.

Conclusion

Respiratory-induced diaphragm motion determined on 4DCT does not accurately predict the daily respiratory-induced diaphragm motion observed on CBCTs, as the amplitude and baseline position differed statistically significantly in the majority of patients. Regular monitoring of respiratory motion during the treatment course using CBCTs could yield a higher accuracy when a daily adaptation to the actual breathing amplitude takes place.

https://ift.tt/2QKoBI5

Clinical outcomes of image-guided proton therapy for histologically confirmed stage I non-small cell lung cancer

Abstract

Background

Two prospective phase II trials were designed to assess the efficacy and safety of image-guided proton therapy (IGPT) for either medically inoperable or operable stage I non-small cell lung cancer (NSCLC). The present study reports the interim results of these trials.

Methods

Fifty-five patients with histologically confirmed stage I NSCLC (IA in 33 patients and IB in 22 patients; inoperable in 21 patients and operable in 34 patients) who received IGPT between July 2013 and February 2017 were analyzed. The median patient age was 71 years (range: 48–88 years). IGPT with fiducial metallic marker matching was performed for suitable patients, and a respiratory gating method for motion management was used for all treatments. Peripherally located tumors were treated with 66 Gy relative biological effectiveness equivalents (Gy(RBE)) in 10 fractions (n = 49) and centrally located tumors were treated with 72.6 Gy(RBE) in 22 fractions (n = 6). Treatment associated toxicities were evaluated using Common Toxicity Criteria for Adverse Events (v.4.0).

Results

Median follow-up was 35 months (range: 12–54 months) for survivors. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 87% (95% confidence interval: 73–94%), 74% (58–85%), and 96% (83–99%), respectively. Fiducial marker matching was used in 39 patients (71%). Grade 2 toxicities observed were radiation pneumonitis in 5 patients (9%), rib fracture in 2 (4%), and chest wall pain in 5 (9%). There were no grade 3 or higher acute or late toxicities.

Conclusions

IGPT appears to be effective and well tolerated for all patients with stage I NSCLC.

Trial registration

Lung-001, 13–02-09 (9), registered 11 June 2013 and Lung-002, 13–02-10 (10), registered 11 June 2013.

https://ift.tt/2A3jfSo

Correction to: Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung

In the original publication, the sixth author name was published incorrectly as Matthew Stein. The correct author name should read as Matthew K Stein.

https://ift.tt/2C8yZFd

Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma

Abstract

Background

Conventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar).

Methods

Circulating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (¹⁸F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments.

Results

We found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (¹⁸F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects.

Conclusion

These results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.

https://ift.tt/2OO2DXe

Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

Abstract

Background

We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel.

Methods

Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables.

Results

Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome.

Conclusions

De novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS.

Trial registration

Retrospectively registered on EudraCT N° 2009–017020-59 and NCT01303497 (February 24, 2011).

https://ift.tt/2NBsugb

Development of acquired resistance to lapatinib may sensitise HER2-positive breast cancer cells to apoptosis induction by obatoclax and TRAIL

Abstract

Background

Lapatinib has clinical efficacy in the treatment of trastuzumab-refractory HER2-positive breast cancer. However, a significant proportion of patients develop progressive disease due to acquired resistance to the drug. Induction of apoptotic cell death is a key mechanism of action of lapatinib in HER2-positive breast cancer cells.

Methods

We examined alterations in regulation of the intrinsic and extrinsic apoptosis pathways in cell line models of acquired lapatinib resistance both in vitro and in patient samples from the NCT01485926 clinical trial, and investigated potential strategies to exploit alterations in apoptosis signalling to overcome lapatinib resistance in HER2-positive breast cancer.

Results

In this study, we examined two cell lines models of acquired lapatinib resistance (SKBR3-L and HCC1954-L) and showed that lapatinib does not induce apoptosis in these cells. We identified alterations in members of the BCL-2 family of proteins, in particular MCL-1 and BAX, which may play a role in resistance to lapatinib. We tested the therapeutic inhibitor obatoclax, which targets MCL-1. Both SKBR3-L and HCC1954-L cells showed greater sensitivity to obatoclax-induced apoptosis than parental cells. Interestingly, we also found that the development of acquired resistance to lapatinib resulted in acquired sensitivity to TRAIL in SKBR3-L cells. Sensitivity to TRAIL in the SKBR3-L cells was associated with reduced phosphorylation of AKT, increased expression of FOXO3a and decreased expression of c-FLIP. In SKBR3-L cells, TRAIL treatment caused activation of caspase 8, caspase 9 and caspase 3/7. In a second resistant model, HCC1954-L cells, p-AKT levels were not decreased and these cells did not show enhanced sensitivity to TRAIL. Furthermore, combining obatoclax with TRAIL improved response in SKBR3-L cells but not in HCC1954-L cells.

Conclusions

Our findings highlight the possibility of targeting altered apoptotic signalling to overcome acquired lapatinib resistance, and identify potential novel treatment strategies, with potential biomarkers, for HER2-positive breast cancer that is resistant to HER2 targeted therapies.

https://ift.tt/2OPqIwN

Combining genomic analyses with tumour-derived slice cultures for the characterization of an EGFR -activating kinase mutation in a case of glioblastoma

Abstract

Background

Epidermal growth factor receptor (EGFR) gene alterations and amplification are frequently reported in cases of glioblastoma (GBM). However, EGFR-activating mutations that confer proven sensitivity to tyrosine kinase inhibitors (TKIs) in lung cancer have not yet been reported in GBM.

Case presentation

Using next-generation sequencing, array comparative genomic hybridization and droplet digital PCR, we identified the p.L861Q EGFR mutation in a case of GBM for the first time. The mutation was associated with gene amplification. L861Q may be a clinically valuable mutation because it is known to sensitize non-small-cell lung cancers to treatment with the second-generation EGFR TKI afatinib in particular. Furthermore, we used slice culture of the patient's GBM explant to evaluate the tumour's sensitivity to various EGFR-targeting drugs. Our results suggested that the tumour was not intrinsically sensitive to these drugs.

Conclusions

Our results highlight (i) the value of comprehensive genomic analyses for identifying patient-specific, targetable alterations, and (ii) the need to combine genomic analyses with functional assays, such as tumour-derived slice cultures.

https://ift.tt/2NzJQu8

A molecular and staging model predicts survival in patients with resected non-small cell lung cancer

Abstract

Background

The current TNM staging system is far from perfect in predicting the survival of individual non-small cell lung cancer (NSCLC) patients. In this study, we aim to combine clinical variables and molecular biomarkers to develop a prognostic model for patients with NSCLC.

Methods

Candidate molecular biomarkers were extracted from the Gene Expression Omnibus (GEO), and Cox regression analysis was performed to determine significant prognostic factors. The survival prediction model was constructed based on multivariable Cox regression analysis in a cohort of 152 NSCLC patients. The predictive performance of the model was assessed by the Area under the Receiver Operating Characteristic Curve (AUC) and Kaplan–Meier survival analysis.

Results

The survival prediction model consisting of two genes (TPX2 and MMP12) and two clinicopathological factors (tumor stage and grade) was developed. The patients could be divided into either high-risk group or low-risk group. Both disease-free survival and overall survival were significantly different among the diverse groups (P < 0.05). The AUC of the prognostic model was higher than that of the TNM staging system for predicting survival.

Conclusions

We developed a novel prognostic model which can accurately predict outcomes for patients with NSCLC after surgery.

https://ift.tt/2OLXTRZ

Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2OPmV2x

The Association Between Renal Tubular Dysfunction and Zinc Level in a Chinese Population Environmentally Exposed to Cadmium

Abstract

Studies in vivo and in vitro have shown a protective effect of zinc against renal dysfunction caused by cadmium exposure. However, limited human data is available. In this study, we evaluated the association between renal tubular dysfunction and body zinc burden in a Chinese population exposed to cadmium. A total of 331 subjects (170 women and 161 men) living in control and cadmium-polluted area were included. Blood cadmium (BCd), urinary cadmium (UCd), serum zinc (SZn), zinc in hair (HZn), Zn/Cd ratio, and urinary β₂Microglobulin (UBMG) were measured. The median UCd, BCd, SZn, and HZn were 2.8 and 13.6 μg/g cr, 1.3 and 12.2 μg/L, 1.31 and 1.12 mg/L, and 0.14 and 0.12 mg/g in subjects living in control and polluted areas. The UBMG level of subjects living in the polluted area was significantly higher than that of the control (0.27 vs 0.11 mg/g cr, p < 0.01). SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or 0.01). Subjects with high SZn concentrations (≥ 1.62 mg/L) had reduced risks of elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07–0.99)] after controlling for multiple covariates compared with those with lower zinc levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95% CI 0.02–0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio were 0.40 (95% CI 0.19–0.84), 0.14 (95% CI 0.06–0.37), and 0.01 (95% CI 0.02–0.18) for renal dysfunction compared with those of the first quartile, respectively. For those subjects with high level of UCd, high level of SZn and HZn also had reduced risks of elevated UBMG. The results of the present study show that high zinc body burden is associated with a decrease risk of renal tubular dysfunction induced by cadmium. Zinc nutritional status should be considered in evaluating cadmium-induced renal damage.

https://ift.tt/2A3IOTz

RETRACTED ARTICLE: Levels of Toxic Elements in Tea Brands Commercialized in Egypt Using Optimized Dual-Pulsed Laser-Induced Spectral Analysis Spectrometer

https://ift.tt/2kQ4s5d

EIF1AX and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC [Research Articles]

Translation initiation is orchestrated by the cap binding and 43S pre-initiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX is enriched in advanced thyroid cancers, where it displays a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer. EIF1AX-A113spl variants stabilize the PIC and induce ATF4, a sensor of cellular stress, which is co-opted to suppress EIF2α phosphorylation, enabling a general increase in protein synthesis. RAS stabilizes c-MYC, an effect augmented by EIF1AX-A113spl. ATF4 and c-MYC induce expression of aminoacid transporters and enhance sensitivity of mTOR to aminoacid supply. These mutually reinforcing events generate therapeutic vulnerabilities to MEK, BRD4 and mTOR kinase inhibitors.

https://ift.tt/2ybZQh8

Study: Atezolizumab Improves Survival in SCLC [News in Brief]

Promising data for checkpoint inhibitor plus chemo could lead to new first-line treatment option for small cell lung cancer.

https://ift.tt/2PswRfw

High Urinary Iodine Concentration Among Breastfed Infants and the Factors Associated with Iodine Content in Breast Milk

Abstract

Iodine deficiency in infants leads to delayed growth and development. Some studies have reported iodine deficiency among infants and lactating women. We assessed iodine status in infants and lactating women, as well as the iodine content in breast milk. A cross-sectional study enrolled mother-infant pairs (infants aged 4–6 months), who visited Well Child Clinic at Ramathibodi Hospital, Bangkok, Thailand. Infants were classified by feeding type as breastfed (BF), mixed breastfed and formula-fed (MF), and formula-fed (FF). Demographic and perinatal data were collected. The urinary iodine concentration (UIC) of infants and lactating women, and breast milk iodine concentration (BMIC) were analyzed. Seventy-one infants were enrolled. The median UIC of infants was 282 mcg/L. Breastfed infants had higher median UIC than formula-fed infants (553 vs. 192 mcg/L; p = 0.002). Forty-eight percent of infants had a UIC more than 300 mcg/L. The median UIC and BMIC of lactating women were 149 and 255 mcg/L, respectively. Among the BF group, the infant UIC was correlated with maternal UIC (r_s = 0.857, p = 0.014). Multiple linear regression showed the BMIC to be associated with maternal UIC (β = 4.03, 95% CI [1.34, 6.71]) and maternal weight (β = 8.26, 95%CI [2.76, 13.77]). Iodine nutrition among our study population was adequate. The median UIC of infants and lactating mothers were 282 and 149 mcg/L, respectively. Breastfed infants had a significantly higher median UIC than formula-fed infants. The BMIC was associated with maternal UIC and maternal weight.

https://ift.tt/2QN71TR

Effect of Dietary Zinc-Nanoparticles on Growth Performance, Anti-Oxidative and Immunological Status of Fish Reared Under Multiple Stressors

Abstract

Zinc is one of the essential micronutrients that can be obtained via water and diet in aquatic animals to meet their physiological needs. The present study was designed to understand the effect of the supplementation of zinc nanoparticles (Zn-NPs) in mitigating abiotic and biotic stress in Pangasius hypophthalmus. Two zinc nanoparticle-incorporated diets with 10 and 20 mg/kg nanoparticles and a control without zinc nanoparticles were formulated. To study the effect of formulated feeds on stress tolerance, fish were exposed to sublethal dose (4 ppm) of Pb (lead) and temperature at 34 °C. Two hundred and seventy-three fish were randomly distributed into seven treatment groups in triplicates, namely a control group (no Zn-NPs and no Pb and temperature exposure, Ctr/Ctr), control diet fed and exposed to Pb (Ctr/Pb), control diet fed and concurrently exposed to Pb and temperature (Pb-T/Ctr), and Zn-NPs 10 and 20 mg/kg diet with or without stressors (Zn-NPs 10 mg/kg, Zn-NPs 20 mg/kg, Pb-T/Zn-NPs 10 mg/kg, Pb-T/Zn-NPs 20 mg/kg). The effect of Zn-NPs on growth performance, stress biomarkers, biochemical and immunological responses, and survival of P. hypophthalmus following challenge with pathogenic bacteria were evaluated. The growth performance was noticeably (p < 0.01) enhanced, and anti-oxidative stress (catalase, superoxide dismutase, and glutathione-s-transferase) significantly reduced in the Zn-NPs supplemented groups. Similarly, immunological parameters such as total protein, albumin, globulin, and A/G ratio significantly improved, and stress biomarkers such as blood glucose, cortisol, and HSP 70 were reduced in Zn-NPs supplemented groups. Overall, the results suggest that supplementation of dietary Zn-NPs with less concentration in the diet has a definitive role in the mitigation of abiotic and biotic stress in P. hypophthalmus.

https://ift.tt/2QGgGeB

High Doses of Boron Have No Protective Effect Against Nephrolithiasis or Oxidative Stress in a Rat Model

Abstract

Boron plays roles in the metabolism of calcium, vitamin D, steroid hormones, healthy bone development, and maintenance of cell membranes. The biological effects of boron are dose-dependent but follow a U-shaped pattern, rendering it important to define the active range. The studies of Bahadoran et al. on rats and Naghii et al. on humans showed that low doses of boron (3 and 10 mg/day) prevented kidney stone formation. The aim of this study was to determine whether high doses of boron have an anti-urolithiatic or antioxidant effect on nephrolithiasis in an experimental rat model. The study was conducted on 50 adult male Wistar rats randomized to five groups. Nephrolithiasis was induced with water containing 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC). This treatment was given to animals in all groups for 10 days, except the positive and negative controls. Simultaneously, groups 2, 3, and 4 were given boric acid via gavage at doses of 25, 50, and 100 mg/kg/day (equivalent to 4/8/16 mg boron respectively) as the source of boron. Animals in the negative and positive control groups were given 6 μL/g distilled water without boric acid. At day 10, intra-cardiac blood samples were drawn from all animals. The right and left kidneys were removed for biochemical and histopathological examinations, respectively. The groups were compared with respect to serum urea, creatinine, calcium, phosphorous, total antioxidant status (TAS), total oxidant status (TOS), serum paraoxonase (PON1) activity, tissue calcium and oxalate levels, and stone burden as determined by histopathological examination. Serum urea and creatinine levels were significantly higher (p < 0.001 and p < 0.05, respectively), while serum calcium and phosphorous levels were significantly lower (p < 0.001 and p < 0.001, respectively), in animals given EG/AC compared to negative controls. No significant differences were detected in serum calcium, phosphorous, urea, or creatinine levels between animals treated with boron and positive controls (p > 0.05). Serum PON1 activity was significantly lower in animals given EG/AC than in negative controls (p < 0.001), while no significant difference in serum PON1 level was detected between rats treated with boron and positive controls. No significant differences were detected in vitamin D, TAS, TOS, tissue calcium, or tissue oxalate levels among groups. No stone formation was detected on histopathological examination in negative controls. No significant differences were found in stone formation between rats treated with boron and positive controls. Based on this study, high doses of boron had no protective effect against nephrolithiasis and oxidative stress.

https://ift.tt/2A46LKF

Relationship of Dietary and Serum Zinc with Depression Score in Iranian Adolescent Girls

Abstract

Zinc deficiency, which is common among Iranian populations, is believed to play a crucial role in the onset and progression of mood disorders such as depression in different stages of life. We have therefore investigated the relationship between serum/dietary zinc status and depression scores among adolescent girls living in northeastern Iran. Serum zinc was measured by flame atomic absorption (Varian AA240FS) and the mean zinc intake was assessed using 3-day food record. A validated Persian version of the Beck Depression Inventory (BDI) was used to determine the severity of depressive symptoms for all subjects. Data were analyzed using SPSS 18 software. There was a statistically significant correlation between dietary zinc intake and serum zinc concentration (r = 0.117, p = 0.018). Dietary intake of zinc (7.04 ± 4.28 mg/day) was significantly lower among subjects with mild to severe depression symptoms than those with no or minimal depression symptoms (8.06 ± 3.03 mg/day). Dietary zinc intake was inversely correlated with depression score (r = 0.133, p = 0.008). However, there was no significant difference in serum zinc concentrations among individuals with no or minimal and mild to severe depression symptoms (p = 0.5). Dietary zinc intake, but not serum zinc concentration, was inversely associated with depression symptoms. Therefore, controlled clinical trials are needed to determine the efficacy of zinc supplementation in the treatment of depression disorders.

https://ift.tt/2QGADSM

Gold and Silver Nanoparticles Biomimetically Synthesized Using Date Palm Pollen Extract - Induce Apoptosis and Regulate p53 and Bcl-2 Expression in Human Breast Adenocarcinoma Cells

Abstract

Recently, several attempts have been made to use the phytopharmaceuticals from plant extracts as reducing, capping and stabilizing agents for the biomimetic synthesis of various metal nanoparticles conjugated to the phytopharmaceuticals. These biogenic metal nanoparticles are non-toxic and can be used as contrast agents, drug delivery vehicles and photothermal agents for cancer therapy. Herein, we report the synthesis of both silver and gold nanoparticles using the pollen extract of Phoenix dactylifera (Date Palm), characterization using UV-visible spectroscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy, quantitation of phytochemicals capping the nanoparticles using Folin – Ciocalteu's method, cytotoxicity studies on MCF-7 breast cancer cells, cancer cell death analysis using fluorescent microscopy, and modulation of expression of the pro-apoptotic p53 and anti-apoptotic Bcl-2 proteins. The biosynthesis resulted in stable and poly-dispersed silver nanoparticles and gold nanoparticles, exhibiting strong and broad surface plasmon absorption peaks. The elemental analysis confirmed the presence of gold and silver of high purity and also the organic moieties from the plant extract acting as capping and stabilizing agents. The biogenic nanoparticles also exhibited dose-dependent cytotoxicity on MCF-7 cells and showed signs of apoptotic cell death. Immunoassays revealed the upregulation of the pro-apoptotic protein p53 and down-regulation of the anti-apoptotic protein Bcl-2 after the nanoparticle treatment.

https://ift.tt/2QGgITL

Pregnancy Alters Renal and Blood Burden of Mercury in Females

Abstract

Methylmercury (CH₃Hg⁺), a common environmental toxicant, has serious detrimental effects in numerous organ systems. We hypothesize that a significant physiological change, like pregnancy, can alter the disposition and accumulation of mercury. To test this hypothesis, pregnant and non-pregnant female Wistar rats were exposed orally to CH₃Hg⁺. The amount of mercury in blood and total renal mass was significantly lower in pregnant rats than in non-pregnant rats. This finding may be due to expansion of plasma volume in pregnant rats and dilution of mercury, leading to lower levels of mercury in maternal blood and kidneys.

https://ift.tt/2A46DLb

Determination of Quality Criteria that Allow Differentiation Between Honey Adulterated with Sugar and Pure Honey

Abstract

This study used various parameters of honey to develop a potentially more robust approach to the detection of adulterated honey. For this purpose, 25 multifloral, natural honey samples and 20 samples of adulterated honey produced by bees that had been fed supplementary sucrose syrup were analysed. The mean total phenolic content of the natural honeys was considerably higher than in the adulterated honeys at 157 ± 13 and 35.2 ± 7.3 mg GAE/100 g, respectively. Similarly, considerable variation was determined between natural and adulterated honeys in terms of total flavonoids (3.3 ± 0.3 and 2.1 ± 0.4 mg QE/100 g, respectively), antiradical activity (87.9 ± 12 and 163 ± 11 mg/mL, respectively) and proline content (202 ± 26 and 71.1 ± 21.6 mg/kg, respectively.) The potassium, phosphorus, calcium and magnesium contents of natural honeys were also higher than in adulterated honeys (P < 0.01). In conclusion, the determination of the proline level, phenolic content, antioxidant activity and mineral profile may collectively provide a more holistic method approach to the differentiation of natural and adulterated honey, and also for comparing their food values.

https://ift.tt/2QGgEU1

Ameliorative Effects of Selenium in ZnO NP-Induced Oxidative Stress and Hematological Alterations in Catla catla

Abstract

Various applications of zinc oxide nanoparticles (ZnO NPs) can increase pollution in aquatic environments. Consequently, pollution can cause toxicity in fish as indicated by oxidative stress, hematotoxicity, and changes in gill and liver histology. Selenium is known for its antioxidant potential in scavenging the free radicals generated during ZnO NP-induced oxidative stress. This study tested the ameliorative role of selenium against ZnO NP-induced toxicity in freshwater fish Catla catla. Four groups of replicated fish, representing control, selenium-treated, ZnO NP-treated, and ZnO NPs+selenium-treated, were used in this study. The ZnO NPs (40 mg l⁻¹) were given to fish in water whereas selenium (50 μg kg⁻¹) was given as sodium selenite in feed. After 28 days of exposure, the fish specimens were processed to collect samples of blood, gills, and liver. The results demonstrated that the consumption of selenium containing feeds protected the C. catla from ZnO NP-induced toxicity and oxidative stress. The use of selenium containing feeds appeared to have reduced the contents of glutathione S-transferase (GST) and glutathione reduced (GSH), and increased the level of catalase (CAT) and superoxide dismutase (SOD). Furthermore, the consumption of selenium in feeds improved the hematological parameters in ZnO NP-treated fish. This study suggests that dietary selenium might be able to ameliorate ZnO NP-induced toxicity in fish.

https://ift.tt/2A46Ait

Endogenous Hydrogen Sulfide Promotes Apoptosis via Mitochondrial Pathways in the Livers of Broilers with Selenium Deficiency Exudative Diathesis Disease

Abstract

Hydrogen sulfide (H₂S), an endogenous gasotransmitter, plays an important role in apoptosis. Exudative diathesis (ED) disease is associated with dietary selenium (Se) deficiency in broilers. The liver is one of the target organs of Se deficiency; however, little is known about the effect of H₂S on apoptosis via mitochondrial pathways in the livers of broilers with ED disease. In the present study, we aimed to investigate the correlation between endogenous H₂S and mitochondrial-mediated apoptosis in the livers of broilers with ED disease, as induced by Se deficiency. One hundred twenty healthy, 1-day-old broilers were randomly assigned to one of two groups (60 each) based on diet: Basal diet (control group, 0.2 mg/kg Se) or a low-Se diet (−Se group, 0.033 mg/kg Se). At day 20, 15 broilers of a similar weight were sacrificed from the control group, while the same number of broilers were euthanatized from the −Se group when displaying typical symptoms of ED between days 18 and 25. The livers were collected, and apoptosis was measured using a TUNEL assay. Additionally, H₂S concentration, the expression of H₂S synthases of cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as mitochondrial apoptosis-related genes of Bcl-2, Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53, were examined in livers. The results indicated that Se deficiency could induce apoptosis in the livers of broilers. Swelling, fractures, and vacuolization were visible in the mitochondrial cristae in the livers of the −Se group. The expression of H₂S synthase-related genes and H₂S concentration was significantly enhanced (P < 0.05) in the livers of the −Se group compared to controls. Moreover, a low-Se diet downregulated (P < 0.05) the level of Bcl-2 and upregulated (P < 0.05) the levels of Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53. These results suggest that an H₂S increase in the livers of ED broilers, which was induced by Se deficiency, is related to apoptosis mediated by mitochondrial pathways.

https://ift.tt/2QHokFw

An Advanced Formulation of a Magnesium Dietary Supplement Adapted for a Long-Term Use Supplementation Improves Magnesium Bioavailability: In Vitro and Clinical Comparative Studies

Abstract

While general recommendations are for 300-mg magnesium intake a day, an advanced low-dose formulation of magnesium chloride, ChronoMag®, was designed to provide 100 mg of magnesium element, thus decreasing the risk of gastrointestinal side effects and allowing long-term supplementation in health conditions related to low magnesium levels. The present study aimed to compare magnesium release profile and bioavailability between this patented low-dose continuous-release magnesium chloride tablet (100 mg magnesium element) and a reference tablet at the usually prescribed dose (300 mg magnesium element). Magnesium release profile was determined by dissolving the tablets in solutions simulating the gastrointestinal tract environment. A randomized double-blind crossover controlled trial of ChronoMag® versus reference tablet (3 × 100 mg magnesium element tablets) in 12 normo-magnesemic healthy volunteers was conducted to evaluate the bioavailability of the patented magnesium chloride tablets (two 50 mg magnesium tablets, once-a-day intake). While the reference tablet released 100% of its magnesium within 1 h of dissolution, release from the magnesium chloride formulation was continuous for 6 h. Cumulative urinary magnesium levels compared to those with the reference tablet were 76% (0–5 h), 89% (0–10 h), and 87% (0–24 h). Elimination after 24 h was fairly similar with both supplements. Our results suggest that the new magnesium chloride formulation, providing continuous low-dose magnesium release throughout the gastrointestinal tract, improves absorption and bioavailability. This formulation conforms to the physiological mechanism of magnesium absorption throughout the digestive tract, allowing high absorption, and may improve gastrointestinal tolerance in long-term use.

https://ift.tt/2A46uY9

Association of TSHR Gene Copy Number Variation with TSH Abnormalities

Abstract

Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As³⁺–Ce⁴⁺ catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p = 0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC > 200 μg/l (OR = 1.49, 95% CI = 1.01–2.22) and the TSHR gene (OR = 6.01, 95% CI = 1.96–18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.

https://ift.tt/2QKcF9f