Pyrimethamine has been used principally to treat infections from protozoan parasites. Although previous studies have shown that pyrimethamine exhibited anticancer activity by inducing cellular apoptosis, there are none that show that pyrimethamine possesses anticancer activity with respect to ovarian cancer. We examined the roles of pyrimethamine on apoptosis and proliferation, DNA damage, and cell cycle distribution of human ovarian cancer cell lines in vitro. To investigate the antitumor efficacy of pyrimethamine in vivo, we established two intraperitoneal ovarian carcinoma models in nude mice. Pyrimethamine significantly induced apoptosis of ovarian cancer cells via growth inhibition, cell cycle arrest, and nuclear DNA damage in vitro and manifested antitumor activity by inhibiting tumor growth, thereby prolonging the survival time of tumor-bearing mice. We also demonstrated that pyrimethamine increased the expression of caspase-9 and decreased the expression of X-linked inhibitor of apoptosis protein. In conclusion, the antitumor effects of pyrimethamine were associated with enhanced apoptosis of tumor cells and inhibition of the growth of intratumoral microvessels. Our results indicate that pyrimethamine may provide an effective approach toward inhibiting the growth of ovarian cancer with minimal adverse effects. *Ya Liu and Tao Yi contributed equally to the writing of this article. Correspondence to Hongjing Wang, PhD, Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, No. 20, Section 3, South People's Road, Chengdu, Sichuan 610041, People's Republic of China Tel: +86 028 855 01211; fax: +86 028 855 02822; e-mail: whjscdx@163.com Received July 18, 2018 Accepted December 10, 2018 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2Fawftr
Κυριακή 6 Ιανουαρίου 2019
Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions
Abstract
Purpose
The purpose of this study was to assess whether digital photon counting technology in digital PET/CT influences the quantification of SUVmax in target lesions and regions of reference compared to analog PET/CT before an interchangeable use of either system in follow up studies.
Methods
From January to June of 2018, 100 oncological patients underwent successive PET/CT imaging with digital and analog systems in the same day. Fifty-eight patients underwent analog imaging first and digital imaging thereafter, and 42 patients the other way round. SUVmax was measured in reference regions (liver and mediastinal blood pool) and in the most metabolically active target lesion in each patient. According to the sequence order of PET/CT acquisition, two groups of SUVmax values were obtained, i.e. group 1: analog PET/CT performed first; group 2: digital PET/CT performed first.
Results
Mean SUVmax in the total sample (regardless of the order of PET/CT acquisition) in the target lesions with the analog PET/CT was 8.14 ± 6.39 and the digital 9.97 ± 6.14 (P = 0.000). Total mean SUVmax in the liver with the analog was 4.39 ± 2.59 and the digital 4.46 ± 3.18 (P = 0.477). Total mean SUVmax in the mediastinal blood pool with the analog was 2.30 ± 0.67 and the digital 2.54 ± 0.74 (P = 0.000).
Group 1: mean SUVmax in the target lesions with the analog system was 6.64 ± 4.71 and the digital 9.48 ± 5.60 (P = 0.000). Mean liver SUVmax with the analog was 4.70 ± 2.90 and the digital 4.80 ± 3.72 (P = 0.088). Mediastinal blood pool SUVmax with the analog was 2.33 ± 0.66 and the digital 2.45 ± 0.73 (P = 0.041).
Group 2: mean SUVmax in target lesions with the digital system was 10.63 ± 6.88 and the analog 10.16 ± 7.76 (P = 0.046). Mean liver SUVmax with the digital was 3.99 ± 2.20 and the analog 3.96 ± 2.04 (P = 0.218). Mediastinal blood pool SUVmax with the digital was 2.66 ± 0.75 and the analog 2.27 ± 0.68 (P = 0.000).
No significant differences between both time delays were found.
Conclusions
Improved photon counting technology in the digital PET/CT, and the effect of delayed increased uptake and retention significantly increases SUVmax values. This has to be taken into account before interchangeable use of either system in follow up studies.
http://bit.ly/2AuA9JC
Recurrence Patterns and Long-term Results After Induction Chemotherapy, Chemoradiotherapy, and Curative Surgery in Patients With Locally Advanced Esophageal Cancer
Objective: The long-term follow up data of 2 prospective phase II trials is reported (NCT00072033, NCT00445861), which investigated neoadjuvant chemoradiation followed by surgery in patients with esophageal carcinoma. Postoperative complications as well as prognostic factors and patterns of relapse during long-term observation are shown. Summary of Background Data: Long-term follow-up is often missing in the complex setting of multimodal treatments of esophageal carcinoma; this leads to rather undifferentiated follow-up guidelines for this tumor entity. Methods: In the first trial, patients received induction chemotherapy followed by chemoradiation and surgery. In the second trial, cetuximab was added to the same neoadjuvant treatment concomitant with induction chemotherapy and chemoradiation. Results: Eighty-two patients underwent surgery; the median follow-up time was 6.8 and 6.4 years, respectively. Fifty-five percent were diagnosed with adenocarcinoma, 80% clinically node-positive, 68% received transthoracic esophagectomy, and 32% transhiatal or transmediastinal resection. Five patients died postoperatively in-hospital due to complications (6%). The median overall survival was 4.3 years, and the median event-free survival was 2.7 years. Patients with adenocarcinoma rarely relapsed after a 3-year event-free survival. Whereas patients with residual tumor cells after neoadjuvant therapy primarily experienced relapse within the first 2 postoperative years, this in contrast to several patients with complete remission who also experienced late relapses 4 years after surgery. Conclusion: After curative surgery in a multimodal setting, the histological type and the response to neoadjuvant therapy predicted the time frame of relapse; this knowledge may influence further follow-up guidelines for esophageal carcinoma.http://bit.ly/2AzyaDY
Cancers, Vol. 11, Pages 47: Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety—A Systematic Review with Meta-Analysis
Cancers, Vol. 11, Pages 47: Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety—A Systematic Review with Meta-Analysis
Cancers doi: 10.3390/cancers11010047
Authors: Wen-Liang Yu Zi-Chun Hua
Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 108 cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.
http://bit.ly/2SE91Pu
Enhanced audio-tactile multisensory interaction in a peripersonal task after echolocation
Abstract
Peripersonal space (PPS) is created by a multisensory interaction between different sensory modalities and can be modified by experience. In this article, we investigated whether an auditory training, inside the peripersonal space area, can modify the PPS around the head in sighted participants. The auditory training was based on echolocation. We measured the participant's reaction times to a tactile stimulation on the neck, while task-irrelevant looming auditory stimuli were presented. Sounds more strongly affect tactile processing when located within a limited distance from the body. We measured spatially dependent audio-tactile interaction as a proxy of PPS representation before and after an echolocation training. We found a significant speeding effect on tactile RTs after echolocation, specifically when sounds where around the location where the echolocation task was performed. This effect could not be attributed to a task repetition effect nor to a shift of spatial attention, as no changes of PPS were found in two control groups of participants, who performed the PPS task after either a break or a temporal auditory task (with stimuli located at the same position of echolocation task). These findings show that echolocation affects multisensory processing inside PPS representation, likely to better represent the space where external stimuli, have to be localized.
http://bit.ly/2RD4KhK
Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study
Abstract
Background
A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration.
Methods
Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus < 24 months, and compared their baseline characteristics with Fisher's exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model.
Results
Overall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS ≥24 months versus 20 (38%) with OS < 24 months. Patients with OS ≥24 vs. < 24 months, respectively, had significantly fewer metastatic sites (≤2 metastases: 52% vs. 10%; ≥3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., ≥ lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil (≤ upper limit of normal, 97% vs. 75%) and platelet (≤ upper limit of normal, 82% vs. 50%) levels at baseline and ≥ 1 year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that ≥1 year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration.
Conclusions
The current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration.
Trial registration
ClinicalTrials.gov identifier, NCT00835978. Registered prospectively, February 4, 2009.
http://bit.ly/2CTATcR
Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: therapeutic implications for immune checkpoint inhibitors
Abstract
Background
We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway.
Methods
Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells.
Results
Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1+ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3+ (P = 0.078), CD8+ (P = 0.055), FOXP3+ (P = 0.016), and PD-1+ (P = 0.016) TILs.
Conclusions
There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1+ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti–PD-1 antibody in BM.
http://bit.ly/2TvhOmP
Randomized prospective phase III trial of 68 Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]
Abstract
Background
Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT.
Methods
We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death.
Discussion
This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy.
Acronym
PSMA-SRT Phase 3 trial.
Clinical trial registration
■ IND#130649
◦ Submission: 04.26.2016
◦ Safe-to-proceed letter issued by FDA: 05.25.2016
■ UCLA IRB #18–000484,
■ First submission: 3.27.2018
■ Date of approval: 5.31.2018
■ UCLA JCCC Short Title NUC MED 18–000484
■ NCI Trial Identifier NCI-2018-01518
■ ClinicalTrials.gov Identifier NCT03582774
■ First Submitted: 06.19.2018
■ First Submitted that Met QC Criteria: 06.27.2018
■ First Posted: 07.11.2018
■ Last Update Submitted that Met QC Criteria: 07.17.2018
■ Last Update Posted: 07.19.2018
Trial status
Current Trial Status Active as of 08/13/2018
Trial Start Date 09/01/2018-Actual
Primary Completion Date 09/01/2023-Anticipated
Trial Completion Date 09/01/2024-Anticipated
http://bit.ly/2TxFmaF
An Unusual Etiology for Osteomyelitis in an Immunocompetent Host
A 58-year-old man sustained an open fracture dislocation of the right ankle when he fell from a stepladder while trimming hedges. He underwent irrigation and debridement followed by open reduction internal fixation (ORIF) for the injury. He received antibiotics during admission but not following discharge. The surgical site healed, radiographs showed stable hardware, and he progressed well when seen in orthopedic follow-up. Six months after ORIF he underwent planned removal of prominent lateral ankle hardware. Operative notes indicated no sign of infection at the time of hardware removal, and the surgical incision healed.
http://bit.ly/2C9cE9c
http://bit.ly/2C9cE9c
Effects of cardiovascular and cerebrovascular health events on work and earnings: a population-based retrospective cohort study [Research]
BACKGROUND:
Survivors of acute health events can experience lasting reductions in functional status and quality of life, as well as reduced ability to work and earn income. We aimed to assess the effect of acute myocardial infarction (MI), cardiac arrest and stroke on work and earning among working-age people.
METHODS:For this retrospective cohort study, we used the Canadian Hospitalization and Taxation Database, which contains linked hospital and income tax data, from 2005 to 2013 to perform difference-in-difference analyses. We matched patients admitted to hospital for acute MI, cardiac arrest or stroke with controls who were not admitted to hospital for these indications. Participants were aged 40–61 years, worked in the 2 years before the event and were alive 3 years after the event. Patients were matched to controls for 11 variables. The primary outcome was working status 3 years postevent. We also assessed earnings change attributable to the event. We matched 19 129 particpants who were admitted to hospital with acute MI, 1043 with cardiac arrest and 4395 with stroke to 1 820 644, 307 375 and 888 481 controls, respectively.
RESULTS:Fewer of the patients who were admitted to hospital were working 3 years postevent than controls for acute MI (by 5.0 percentage points [pp], 95% confidence interval [CI] 4.5–5.5), cardiac arrest (by 12.9 pp, 95% CI 10.4–15.3) and stroke (by 19.8 pp, 95% CI 18.5–23.5). Mean (95% CI) earnings declines attributable to the events were $3834 (95% CI 3346–4323) for acute MI, $11 143 (95% CI 8962–13 324) for cardiac arrest, and $13 278 (95% CI 12 301–14 255) for stroke. The effects on income were greater for patients who had lower baseline earnings, comorbid disease, longer hospital length of stay or needed mechanical ventilation. Sex, marital status or self-employment status did not affect income declines.
INTERPRETATION:Acute MI, cardiac arrest and stroke all resulted in substantial loss in employment and earnings that persisted for at least 3 years after the events. These outcomes have consequences for patients, families, employers and governments. Identification of subgroups at high risk for these losses may assist in targeting interventions, policies and legislation to promote return to work.
http://bit.ly/2C7GlHq
68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105
Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes.
Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor.
Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p
Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.
http://bit.ly/2CU6xa8
Association between awareness of nutrition labeling and high-density lipoprotein cholesterol concentration in cancer survivors and the general population: The Korean National Health and Nutrition Examination Survey (KNHANES) 2010–2016
Abstract
Background
Nutrition labeling has been found to affect the amount and type of food intake, with certain groups in the population, such as cancer survivors, being more aware of this information. A higher awareness of nutrition labeling is inversely related to the risk of dyslipidemia. This study therefore assessed the association between awareness of nutrition labeling and high-density lipoprotein cholesterol (HDL-C) concentration among cancer survivors in South Korea and in the general population of subjects without a history of cancer.
Methods
This cross-sectional analysis evaluated 25,156 adults who participated in the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2010 to 2016. Factors influencing the association between awareness of nutrition labeling and HDL-C concentration in cancer survivors and the general population were determined by multiple regression analysis.
Results
Of the 25,156 participants, 2.88% were cancer survivors and 97.12% had no history of cancer. HDL-C concentrations were higher in subjects who were aware of nutrition labeling than in subjects who were not. Checking or using nutrition labeling had a greater effect on the management of HDL-C concentration for cancer survivors than for the general population.
Conclusion
Awareness of nutrition labeling was associated with better outcomes, including higher controlled HDL-C levels, and reductions in factors increasing the risk of coronary artery disease and cancer, especially in cancer survivors. Health policymakers or medical professionals should develop programs to promote the use of nutrition labeling among cancer survivors in South Korea.
http://bit.ly/2Fdc79a
Total hysterectomy versus uterine evacuation for preventing post-molar gestational trophoblastic neoplasia in patients who are at least 40 years old: a systematic review and meta-analysis
Abstract
Background
The clinical value of total hysterectomy for patients with hydatidiform mole (HM) being at least 40 years old remains highly controversial. Since the practice of hysterectomy has been applied globally for decades, there is an urgent need to perform a systematic review to assess its risks and benefits.
Methods
Six electronic databases, including four English databases and one Chinese database, were searched from the inception of each database till October 6th 2017. Studies were included if they: 1) were human studies, 2) explicitly indicated exposure to hysterectomy, 3) explicitly indicated control to uterine evacuation, 4) explicitly indicated the participants were older patients with HM being at least 40 years in age, 5) compared the outcome of interest as the incidence of post-molar GTN. Two authors independently conducted the literature search, study selection, data extraction. Pooled odds ratios were analyzed using Review Manager 5.3.
Results
The overall pooled effect size of total hysterectomy had a significant advantage in preventing post-molar gestational trophoblastic neoplasia over uterine evacuation with an OR of 0.19 (95% CI, 0.08–0.48; P = 0.0004) and a low heterogeneity (I2 = 21%, P = 0.28). Subgroup analysis and sensitivity analysis also showed similar results.
Conclusions
Total hysterectomy, as compared to uterine evacuation, is a better therapeutic method for patients with HM being at least 40 years old unless fertility is still desired.
http://bit.ly/2LUr0yr
Decreased mean platelet volume predicts poor prognosis in metastatic colorectal cancer patients treated with first-line chemotherapy: results from mCRC biomarker study
Abstract
Background
Metastatic colorectal cancer (mCRC) is a major cause of death of malignant tumor and the valuable prognostic biomarker for chemotherapy is crucial in decreasing mortality. Previous studies have proved the prognostic value of the mean platelet volume (MPV) in survival of primary operable CRC patients. However, the prognostic impact of MPV in mCRC is still unclear. In this study, we aimed to clarify the prognostic role of MPV in mCRC undergoing standard first-line chemotherapy.
Methods
From January 2012 to December 2016, we conducted a retrospective clinical study included 264 mCRC patients (NCT03532711). All the enrolled patients received the standard oxaliplatin-based or irinotecan-based chemotherapy. The association between the baseline MPV and clinicopathological features were examined.
Results
Univariate analysis revealed that decreased MPV, the platelet counts (PLT), platelet-to-lymphocyte ratio (PLR) and the platelet crit (PCT) were significantly associated with inferior overall survival (OS) (p < 0.05). On multivariate analysis, elevated PLR was significant prognostic factors for OS, with hazard ratios of (HR:1.006, 95% CI:1.001–1.011, p = 0.01) while MPV was not, respectively (p < 0.05).
Conclusions
Our study demonstrated that the baseline MPV level may act as a predictive factor for survival in mCRC patients undergoing standard chemotherapy.
Trial registration
This study was retrospectively registered in date May the 20th 2018. The registration number (TRN) of this study was NCT03532711.
http://bit.ly/2saV2Fh
Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program
Abstract
Background
Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking.
Methods
This was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6 cm was allowed, visceral disease was excluded) received radium-223, 55 kBq/kg intravenously, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline.
Results
Seven hundred eight patients received ≥1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3–4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease.
Conclusions
Using radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies.
Trial registration
The study was registered with ClinicalTrials.gov, number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012–000075-16 on April 4, 2012.
http://bit.ly/2LXWfJe
miR-632 promotes gastric cancer progression by accelerating angiogenesis in a TFF1-dependent manner
Abstract
Background
Gastric cancer (GC) is a common malignant disease worldwide. Aberrant miRNAs expression contributes to malignant cells behaviour, and in preclinical research, miRNA targeting has shown potential for improving GC therapy. Our present study demonstrated that miR-632 promotes GC progression in a trefoil factor 1 (TFF1)-dependent manner.
Methods
We collected GC tissues and serum samples to detect miR-632 expression using real-time PCR. A dual-luciferase reporter assay was used to identify whether miR-632 directly regulates TFF1 expression. Tube formation and endothelial cell recruitment assays were performed with or without miR-632 treatment. Western blot and in situ hybridization assays were performed to detect angiogenesis and endothelial recruitment markers that are affected by miR-632.
Results
Our results showed that miR-632 is highly expressed in GC tissue and serum and negatively associated with TFF1 in GC. miR-632 improves tube formation and endothelial cell recruitment by negatively regulating TFF1 in GC cells. Recombinant TFF1 reversed miR-632-mediated angiogenesis. TFF1 is a target gene of miR-632.
Conclusions
Our study demonstrated that miR-632 promotes GC progression by accelerating angiogenesis in a TFF1-dependent manner. Targeting of miR-632 may be a potential therapeutic approach for GC patients.
http://bit.ly/2sfGEva
What are the social predictors of accident and emergency attendance in disadvantaged neighbourhoods? Results from a cross-sectional household health survey in the north west of England
Objectives
The aim of this study was to identify the most important determinants of accident and emergency (A&E) attendance in disadvantaged areas.
Design, setting and participantsA total of 3510 residents from 20 disadvantaged neighbourhoods in the North West Coast area in England completed a comprehensive public health survey.
Main outcome measuresParticipants were asked to complete general background information, as well as information about their physical health, mental health, lifestyle, social issues, housing and environment, work and finances, and healthcare service usage. Only one resident per household could take part in the survey. Poisson regression analysis was employed to assess the predictors of A&E attendance frequency in the previous 12 months.
Results31.6% of the sample reported having attended A&E in the previous 12 months, ranging from 1 to 95 visits. Controlling for demographic and health factors, not being in employment and living in poor quality housing increased the likelihood of attending an A&E service. Service access was also found to be predictive of A&E attendance insofar as there were an additional 18 fewer A&E attendances per 100 population for each kilometre closer a person lived to a general practitioner (GP) practice, and 3 fewer attendances per 100 population for each kilometre further a person lived from an A&E department.
ConclusionsThis is one of the first surveys to explore a comprehensive set of socio-economic factors as well as proximity to both GP and A&E services as predictors of A&E attendance in disadvantaged areas. Findings from this study suggest the need to address both socioeconomic issues, such as employment and housing quality, as well as structural issues, such as public transport and access to primary care, to reduce the current burden on A&E departments.
http://bit.ly/2Az7CTk
Development and piloting of a highly tailored digital intervention to support adherence to antihypertensive medications as an adjunct to primary care consultations
Objectives
This paper describes the systematic development and piloting of a highly tailored text and voice message intervention to increase adherence to medication in primary care.
MethodsFollowing the Medical Research Council guidance, this paper describes (a) the systematic development of the theoretical framework, based on review of theories and meta-analyses of effectiveness; (b) the systematic development of the delivery mode, intervention content and implementation procedures, based on consultations, face-to-face interviews, think-aloud protocols, focus groups, systematic reviews, patient and public involvement/engagement input, intervention pre-test; and (c) the piloting of the intervention, based on a 1-month intervention; and follow-up assessment including interviews and questionnaires. The mixed-methods analysis combined findings from the parallel studies complementarily.
Resultsintervention development suggested the target behaviour of the intervention should be the tablets taken at a regular time of the day. It recommended that patients could be more receptive to intervention content when they initiate medication taking or they change prescription plan; and more emphasis is needed to patients' consent process. Intervention piloting suggested high intervention engagement with, and fidelity of, the intervention content; which included a combination of behaviour change techniques, and was highly tailored to patients' beliefs and prescription plan. Patients reported that the intervention content increased awareness about the necessity to take and maintain adherent to medication, reinforced social support and habit formation, and reminded them to take medication as prescribed.
ConclusionTailored automated text and voice message interventions are feasible ways to improve medication adherence as an adjunct to primary care.
Trial registration numberhttp://bit.ly/2SDLcHx
Hypoxia-induced Slug SUMOylation enhances lung cancer metastasis
Abstract
Background
The Slug-E-cadherin axis plays a critical role in non-small-cell lung cancers (NSCLCs) where aberrant upregulation of Slug promotes cancer metastasis. Now, the post-translational modifications of Slug and their regulation mechanisms still remain unclear in lung cancer. Hence, exploring the protein linkage map of Slug is of great interest for investigating the scenario of how Slug protein is regulated in lung cancer metastasis.
Methods
The Slug associated proteins, Ubc9 and SUMO-1, were identified using yeast two-hybrid screening; and in vitro SUMOylation assays combined with immunoprecipitation and immunoblotting were performed to explore the detail events and regulations of Slug SUMOylation. The functional effects of SUMOylation on Slug proteins were examined by EMSA, reporter assay, ChIP assay, RT-PCR, migration and invasion assays in vitro, tail vein metastatic analysis in vivo, and also evaluated the association with clinical outcome of NSCLC patients.
Results
Slug protein could interact with Ubc9 and SUMO-1 and be SUMOylated in cells. Amino acids 130–212 and 33–129 of Slug are responsible for its binding to Ubc9 and protein inhibitor of activated STAT (PIAS)y, respectively. SUMOylation could enhance the transcriptional repression activity of Slug via recruiting more HDAC1, resulting in reduced expression of downstream Slug target genes and enhanced lung cancer metastasis. In addition, hypoxia could increase Slug SUMOylation through attenuating the interactions of Slug with SENP1 and SENP2. Finally, high expression Slug and Ubc9 levels were associated with poor overall survival among NSCLC patients.
Conclusions
Ubc9/PIASy-mediated Slug SUMOylation and subsequent HDAC1 recruitment may play a crucial role in hypoxia-induced lung cancer progression, and these processes may serve as therapeutic targets for NSCLC.
http://bit.ly/2sm6IVT
A model-based approach to predict short-term toxicity benefits with proton therapy for oropharyngeal cancer
The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensity-modulated radiotherapy (IMRT) for oropharynx cancer, and to use a model-based approach to investigate the added value of PBT in preventing treatment complications.
http://bit.ly/2GW71Rm
A phase I pilot study of pre-operative radiotherapy for prostate cancer: Long-term toxicity and oncologic outcomes
We report the long-term results of a phase I pilot study assessing short-course pre-operative radiotherapy (PreORT) followed by radical prostatectomy in 15 unfavourable intermediate and high-risk prostate cancer (PCa) patients. With median follow-up of 12 years, the incidence of grade 2+ genitourinary and gastrointestinal toxicity were 53.3% and 6.7%, respectively. Biochemical and metastatic disease recurrence occurred in 53.3% and 40% of patients, respectively. Future studies must cautiously select PreORT technique and dose schedule.
http://bit.ly/2REldmc
Statin use after diagnosis of hepatocellular carcinoma and patient survival: findings from a retrospective cohort study
Statin use is associated with lower risk of developing hepatocellular carcinoma (HCC). However, it is unclear whether post-diagnosis statin use is associated with reduced risk of mortality in HCC patients.
http://bit.ly/2Fa2adB
Shorter Disease Duration is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn’s Disease but Not Ulcerative Colitis
Patients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.
http://bit.ly/2Ff5Hq3
Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis
Patients with hepatic venous pressure gradients (HVPGs) ≥10 mmHg and chronic liver disease are often assumed to have cirrhosis. We investigated the association between HVPGs and cirrhosis, using histologic findings as the reference standard. We also assessed the prevalence and characteristics of patients with HVPGs ≥10 mmHg without cirrhosis.
http://bit.ly/2FbNtH0
Substantial Increase in Anesthesia Assistance for Outpatient Colonoscopy and Associated Cost Nationwide
The use of anesthesia assistance (AA) for outpatient colonoscopy has been increasing over the past decade, raising concern over its effects on procedure safety, quality, and cost. We performed a nationwide claims-based study to determine regional, patient-related, and facility-related patterns of anesthesia use as well as cost implications of AA for payers.
http://bit.ly/2Ff5D9N
Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis
Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50–1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH.
http://bit.ly/2FbNmLA
Cardiac Magnetic Resonance Imaging at 7 Tesla
The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.
http://bit.ly/2C3sMZz
A Randomized, Controlled Clinical Trial of Combining Therapy with Traditional Chinese Medicine-Based Psychotherapy and Chinese Herbal Medicine for Menopausal Women with Moderate to Serious Mood Disorder
Objective. To comparatively examine the effectiveness and safety of the combination therapy of traditional Chinese medicine formula Bushen-Shugan granule and psychotherapy (BSSG-P) and Chinese herbal medicine Bushen-Shugan granule (BSSG) alone in the treatment of moderate to serious mood disorder in menopausal women. Methods. In our previous clinical studies, BSSG-P had been proved to be superior to BSSG, psychological treatment, and placebo in improving mild mood disorder in menopausal women. In this study, we analyzed the efficacy of BSSG-P and BSSG in the treatment of moderate to serious mood disorder. Eighty-five eligible participants, who were diagnosed as menopausal women with moderate to serious mood disorder and categorized as kidney deficiency and liver-qi stagnation pattern, were randomly assigned into two groups and treated with BSSG-P or BSSG. They were subjected to an 8-week treatment period and a 4-week follow-up study. The primary outcome instrument was the Greene Climacteric Scale, Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS), respectively. Results. When comparing all time points with baseline, both BSSG-P and BSSG markedly decreased the total score of Greene, SDS, and SAS and the score of each dimension, in which BSSG-P exerted superior effect after 8-week treatment and 4-week follow-up (P0.05). No serious event occurred in both groups, and no significant difference was found between groups in adverse event proportion. Conclusions. BSSG-P was superior to BSSG in improving the physical and psychological symptoms of menopausal women with mood disorder. For patients with moderate mood disorder, BSSG-P showed obvious advantages; however, no superiority was observed for serious mood disorder.
http://bit.ly/2sb7418
Do Different Species of Sargassum in Haizao Yuhu Decoction Cause Different Effects in a Rat Goiter Model?
Sargassum species combined with Glycyrrhiza uralensis is a famous herbal pair in traditional Chinese medicine, as one of the so-called "eighteen antagonistic medicaments." In the Chinese Pharmacopoeia, two different species of Sargassum, Sargassum pallidum and Sargassum fusiforme, are recorded but they are not clearly differentiated in clinical use. In this study, we aimed to determine whether the two species of Sargassum could result in different effects when combined with G. uralensis in Haizao Yuhu Decoction (HYD), which is used for treating thyroid-related diseases, especially goiter. HYD containing S. pallidum or S. fusiforme was administered to rats with propylthiouracil-induced goiter. After 4 weeks, pathological changes in the thyroid tissue and the relative thyroid weight indicated that HYD containing S. pallidum or S. fusiforme protected thyroid tissues from propylthiouracil damage. Neither species increased the propylthiouracil-induced decrease in serum levels of thyroid hormones. However, there were some differences in their actions, and only HYD containing S. fusiforme abated the propylthiouracil-induced elevation of serum thyroid-stimulating hormone levels and activated thyroglobulin mRNA expression.
http://bit.ly/2LTBRsx
Clear Cell Myoepithelial Carcinoma Arising from the Hard Palate with Metastasis to the Lungs
Myoepithelial carcinoma is an uncommon tumor of the salivary glands, most commonly the parotid gland. Clear cell myoepithelial carcinoma is a rare variant with an aggressive behavior. Here, we describe a case of clear cell myoepithelial carcinoma arising from the hard palate in an elderly male who underwent resection of the tumor and postop radiation. Posttreatment imaging demonstrated bilateral pulmonary nodules and a C2 body lesion concerning for metastasis. Biopsy of the lung lesions revealed a monomorphous population of optically clear cells with hyperchromatic and pleomorphic nuclei which were morphologically similar to the prior resection specimen. There are few reported cases of clear cell myoepithelial carcinoma arising from the hard palate, and there are even fewer reports on metastases to the lungs. Due to the low number of reported cases, prognosis and treatment of this neoplasm is not well defined.
http://bit.ly/2SFZvew
Cardiac Arrest in the Airport Revealing Cocaine Body Packing: A Case Report
Ingestion of large amounts of cocaine packages is a well-known method for cross-border transportation. Intestinal obstruction and life-threatening sympathomimetic toxidrome including seizures, ventricular dysrhythmia, and cardiac arrest resulting from the rupture of cocaine packages may occur. Here, we report a case of a 34-year-old pregnant woman who had a sudden cardiac arrest while waiting for her bags at Paris-Charles de Gaulle Airport, France. According to the flight attendants, the patient travelled from Brazil and complained of abdominal pain during the flight. After resuscitation, the patient presented sustained tachycardia and convulsions suggesting cocaine overdose caused by body packing. Once admitted to the hospital, laparotomy was performed allowing the extraction of 50 cocaine packages. Cardiac symptoms were attributed to the rupture of five of the packages. Prehospital and emergency physicians need to be aware of the possibility of cocaine overdose by body packing in patients presenting sudden cardiac arrest in airports.
http://bit.ly/2LS10Uy
Clinical and genetic characterization of de novo double-hit B cell precursor leukemia/lymphoma
Abstract
The 2016 revised World Health Organization (WHO) classification of lymphoid neoplasms included the category of high-grade B cell lymphomas (HGBLs) with combined MYC and BCL2 and/or BCL6 rearrangements (double-hit, DH). However, the clinical features of B cell precursor leukemia (BCP-ALL) that harbor DH genetics remain widely unknown. We performed a retrospective analysis of the German Multicenter Study Group for Adult ALL registry and a literature search for de novo DH-BCP-ALLs. We identified 6 patients in the GMALL registry and 11 patients published in the literature between 1983 and June 2018. Patients of all ages (range, 15–86 years) are affected. There is a high incidence of meningeal disease and other extramedullary disease manifestations. Current treatment approaches are mainly ALL-based and are sufficient to induce first complete remissions, but progression-free survival is only 4.0 months (95% CI, 1.5–6.5 months) and all patients succumb to their disease, once relapsed, with a median survival of 5.0 months (95% CI, 3.1–6.9 months), despite intensive salvage and targeted therapy approaches. Of all patients, only two that attained an initial complete remission were alive at data cutoff. In all cases, the BCL2 gene was rearranged to be in proximity to the IGH locus, whereas MYC had various translocation partners juxtaposed. There was no significant survival difference between IG and non-IG translocation partners (HR, 1.03; 95% CI, 0.33–3.2; p = 0.89). In conclusion, de novo DH-BCP-ALL is an aggressive B cell malignancy with deleterious outcome. Physicians have to be aware of this rare disease subset due to the atypical clinical behavior and especially because latest classification systems do not cover this sub-entity.
http://bit.ly/2SD1aSg
Clinical Effects and Safety of Tongxieyaofang on Diarrhea Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized Trails
Background. Tongxieyaofang (TXYF), a prescription originated from traditional Chinese medicine (TCM), has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). The purpose of this meta-analysis was to investigate whether TXYF was effective and safe for IBS-D. Methods. We searched seven electronic databases including CENTRAL, MEDLINE, PubMed, CNKI, VIP, CBM, and Wanfang Data up to 26 July 2017. Randomized controlled trails (RCTs) were eligible, regardless of blinding. Risk of bias of included trials was evaluated according to the Cochrane Handbook. Results. The total number of participants analyzed in the meta-analysis was 3062, of which 1556 received TXYF, while 1506 received ordinary treatment. The primary outcome was clinical effective rate. Compared with conventional medication which included probiotics, pinaverium bromide, trimebutine, and Oryzanol, TXYF significantly improved the clinical effective rate (n=37, OR: 4.61; 95% CI: 3.67–5.78; P
http://bit.ly/2Ra0Pd0
Bufei Jianpi Granules Reduce Quadriceps Muscular Cell Apoptosis by Improving Mitochondrial Function in Rats with Chronic Obstructive Pulmonary Disease
Background. Cell apoptosis is an important mechanism underlying skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients, and mitochondrial dysfunction is recognized as a central aspect contributing to skeletal muscle deterioration. Bufei Jianpi granules have been confirmed effective for improving motor function in COPD patients, but the specific mechanism for this improved function remains unknown. This study explored the mechanisms by which Bufei Jianpi granules improve cell apoptosis and mitochondrial dysfunction in COPD. Methods. Sprague-Dawley rats were randomized into control, model, Bufei Jianpi, and aminophylline groups. A stable COPD rat model was induced with respective repeated cigarette smoke inhalation and intragastric bacterial infection, and rats were sacrificed after 20 weeks; the quadriceps muscle was harvested from each rat. Skeletal muscle mitochondria were extracted for measurements of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore openings (mPTPs). ATP levels were determined with a firefly luciferase-based ATP assay kit. The rates of cell apoptosis were determined by the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. Cyto C and caspase-3 mRNA and protein levels were measured by qPCR and western blotting. Results. ATP, MMP, and mPTPs were markedly decreased in COPD rats, while cell apoptosis, caspase-3, and Cyto C were increased (P
http://bit.ly/2C4iybz
Selective Inhibition of HIF1α Expression by ZnSO 4 Has Antitumoral Effects in Human Melanoma
Abstract
Zinc as an essential trace metal is a ubiquitous component of various molecules of the cell. Studies indicated that it may modulate functions of various cancer cell types, and can even inhibit metastasis formation in experimental models. In melanoma, zinc was shown to affect melanin production and to induce apoptosis. Using human melanoma cell lines, we have tested the effects of ZnSO4 on cell proliferation, survival, migration as well as in vivo on experimental liver colony formation. We have found that ZnSO4 has antiproliferative and proapoptotic effects in vitro. In SCID mice intraperitoneal administration of ZnSO4 specifically inhibited liver colony formation without affecting primary tumor growth. To reveal the molecular mechanisms of action of zinc in human melanoma, we have tested mRNA expression of zinc finger transcription factors and found a strong inhibitory effect on HIF1α, as compared to WT1 whereas HIF2α and MTF1 expression was unaffected. Immunohistochemical detection of HIF1α protein in liver metastases confirmed its decreased nuclear expression after in vivo ZnSO4 treatment. These data indicate that in human melanoma zinc administration may have an antimetastatic effect due to a selective downregulation of HIF1α.
http://bit.ly/2CPPgig
Enhanced Tumoral MLH1-Expression in MLH1-/PMS2-Deficient Colon Cancer Is Indicative of Sporadic Colon Cancer and Not HNPCC
Abstract
Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is caused by germline mutations of mismatch-repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. MLH1-/PMS2-deficient colorectal carcinomas might be HNPCC-associated but also caused by MLH1-promoter methylation in sporadic colon carcinoma. This study analyzed semiquantitatively whether the MLH1 staining pattern might be indicative of sporadic or HNPCC-associated colorectal cancer. Using a semiquantitative score ranging from 0 (negative) to 12 (maximum immunopositivity) we analyzed MLH1 expression patterns in 130 MLH1-/PMS2-deficient colorectal cancers. The collective consisted of 70 HNPCC-associated colorectal cancers and 60 sporadic colon cancers. In tumor cells of 70 HNPCC-associated colorectal cancers, 64 cases (91.43%) showed no MLH1 staining, 5 cases weak (7.14%) and 1 case (1.43%) stronger staining intensity. In contrast, in tumor cells of 60 sporadic colorectal cancers 45 cases (75.0%) showed no MLH1 staining, 10 cases weak (16.67%) and 5 cases (8.33%) stronger staining intensity to a varying extent. In immunopositive cases, MLH1 showed a characteristic dot-like nuclear staining pattern in the tumor cells. We compared cases with absent to weak MLH1-staining (immunoscores 0 to 2) to cases with elevated immunoscores (3 to 12) detecting a statistically significant difference between HNPCC-associated and sporadic colon cancers (p value = 0.0031, Fisher's exact test). Taken together, enhanced tumoral MLH1 expression in MLH1-/PMS2-deficient colorectal carcinomas seems to be indicative of sporadic origin. In contrast, HNPCC-associated colorectal cancer showed absent or very weak MLH1 immunopositivity. Therefore, this semiquantitative and easy to exert MLH1 immunoscore might help to identify sporadic MLH1-/PMS2-deficient colorectal cancer cases prior to time-consuming methylation analysis.
http://bit.ly/2CRKBN1
Real Life Data on Efficacy and Safety of Azacitidine Therapy for Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia
Abstract
The administration of azacitidine (AZA) was found to be more effective than conventional care regimen (CCR) in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) with lower blast count. We designed a study to determine efficacy and safety of AZA therapy in "real life" patients with MDS, CMML and AML. The study included 83 patients (65% male) with a median age at diagnosis of 68 years. 43 patients were diagnosed with higher-risk MDS, 30 had AML and 10-CMML. Median AZA dose was comparable between treated groups. AZA dose reduction was required for 44% of MDS, 17% of AML and 25% of CMML patients. Complete remission (CR) was achieved in 14% of MDS, 7% of AML and 10% of CMML patients. Overall response rate was following: 27% for MDS, 20% for AML and 20% for CMML. Estimated OS at 12 months was 75% for MDS, 60% for AML and 75% for CMML. Median follow-up for MDS/AML/CMML from AZA initiation to last follow-up was 9.0, 9.4 and 9.4 months, respectively. The most common toxicity of AZA therapy was myelosuppression and infections. AZA treatment was effective in a limited number of patients with acceptable safety profile.
http://bit.ly/2TyH1wM
High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy. Long noncoding RNA (LncRNA) HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been shown to play important roles in the progression of several type cancers. However, the exact role of HOTAIRM1 in PDAC development remains largely unknown. This study aims to evaluate the potential function of HOTAIRM1 in the development and progress of PDAC. HOTAIRM1 expression was measured by RT-qPCR in forty seven paired human PDAC tissues and five PDAC cell lines. SW1990 and PANC-1 cells were transfected with siHOTAIRM1 to achieve HOTAIRM1 silence. MTT assay and colony formation assay were used to detect the effect of HOTAIRM1 knockdown on cell proliferation. The impact of HOTAIRM1 silence on cell cycle and apoptosis was assessed by flow cytometry assay. Transwell migration assay was performed to explore the influence of HOTAIRM1 downregulation on the migratory potential of PDAC cells. Western blot assay was applied to determine the expression changes of cell cycle, apoptosis, and migration-related genes before and after downregulating HOTAIRM1. HOTAIRM1 expression was abnormally upregulated in PDAC tissues and cells when compared with the control samples, and was positively associated with the expression of KRAS gene mutation. In vitro functional experiments, HOTAIRM1 expression was significantly downregulated by transfection with siHOTAIRM1 in SW1990 and PANC cell lines. HOTAIRM1 knockdown attenuated cell proliferation by inducing cell cycle arrest at G0/G1 phase, promoted cell apoptosis, and inhibited cell migration in PDAC cells by regulating related-genes expression. In conclusion, HOTAIRM1 plays a critical role in PDAC progression, which may be a novel diagnostic and rational therapeutic target for the treatment of pancreatic ductal adenocarcinoma.
http://bit.ly/2TvIhR0
Orostachys japonicus A. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats
In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.
http://bit.ly/2ReNqQU
Ultrasonographic Assessment with Three-Dimensional Mode of the Urethral Compression Effect following Sling Surgery with and without Mesh Surgery
Background. The aim of this study was to assess anatomical changes in the urethra at rest and during straining following sling surgery with and without transvaginal mesh surgery (TVM) in women with stress urinary incontinence (SUI) with or without pelvic organ prolapse (POP) using three-dimensional ultrasonography. Methods. 76 women with SUI with or without pelvic organ prolapse after sling surgery. They underwent sling surgery alone (S group, n=36) or concomitant TVM (M group, n=40). All patients underwent urinalysis, pelvic examinations, urodynamic study, 3D perineal ultrasonography, and personal interviews before and 1 year after surgery. The urethral area was calculated from the axial plane of perineal ultrasonography by multiplying π by the long and short axes of the urethral lumen. Results. The axial area of the middle and distal urethra during straining was significantly smaller than at rest in both groups (P
http://bit.ly/2C8zPjE
The Effect of Pelvic Floor Muscles Exercise on Quality of Life in Women with Stress Urinary Incontinence and Its Relationship with Vaginal Deliveries: A Randomized Trial
Introduction. Urinary incontinence (UI) is a health problem affecting the quality of women's lives (QOL) at various life stages. Stress urinary incontinence (SUI) can be caused by previous vaginal deliveries and is especially likely to occur in the perimenopausal period. The most commonly recommended first-choice treatment methods involve exercises for the pelvic floor muscles (PFM). The aim of this study was to assess the impact of isolated PFM exercises and combined training of the PFM and the m.transversus abdominis (TrA) muscle on the QoL of patients with SUI with regard to the number of vaginal deliveries. Material and Methods. 137 women with SUI were qualified for analysis (mean age 53,1 ± 5,5). To assess the effectiveness of PFM training QOL questionnaire was used (ICIQ-LUTS qol). PFM training for groups A (PFM+TrA) and B (PFM) was intended for 12 weeks. Statistica v. 12.0 PL, StatSoft, USA, was used for statistical calculations. Results. The analysis demonstrated that conservative treatment based on the A training program (PFM + TrA) yielded statistically significantly better results than the B program (PFM), with the improvement observed in such QoL domains as the performance of household duties, physical activity and travelling, social limitations, emotions, sleep problems and fatigue, the frequency of changing panty liners, fluid intake control, and embarrassment. Conclusion. Both the combined training of the PFM and the synergistic (TrA) muscle and the isolated PFM exercises improve the QoL of women with SUI. Nonetheless, the combined PFM and TrA muscle physiotherapy is more effective. The exercises for the PFM and the synergistic muscle give better results in women who have given birth fewer than three times than isolated PFM exercises.
http://bit.ly/2RxnWh2
Effects of a New Combination of Medical Food on Endothelial Function and Lipid Profile in Dyslipidemic Subjects: A Pilot Randomized Trial
Nutritional approaches to improve dyslipidemias have been recently developed, but evidences on different medical foods are often incomplete. The main aim of our study was to evaluate the effects on endothelial function, lipid profile, and glucose metabolism of two different combinations of nutraceuticals, first one containing Bergavit (200 mg Citrus bergamia), Omega-3 (400 mg), Crominex 3+ (10 mcg trivalent chromium), and red yeast rice (100 mg; 5 mg monacolin K) and second one containing red yeast rice (200 mg; 3 mg monacolin K), Berberine (500 mg), Astaxanthin (0.5 mg), folic acid (200 mcg), Coenzyme Q10 (2 mg), and Policosanol (10 mg). Fifty subjects affected by dyslipidemia not requiring statin treatment were enrolled in this randomized, blind, controlled trial and submitted to blood sampling for lipid and glucose profiles and instrumental evaluation of endothelial function before and after 6 weeks of treatment with nutraceuticals. Both nutraceutical combinations improved the lipid profile; the nutraceutical containing 5 mg of monacolin K, 200 mg of the extract Citrus bergamia, 400 mg of Omega-3, and 10 mcg of trivalent chromium entailed a significant improvement of endothelial function with enhanced cholesterol lowering effect. In conclusion, this study confirms the positive effect of functional food on lipid profile and endothelial function in absence of major undesirable effects.
http://bit.ly/2GXKsvw
Brucine Suppresses Vasculogenic Mimicry in Human Triple-Negative Breast Cancer Cell Line MDA-MB-231
Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.
http://bit.ly/2RtZMnG
Antegrade Elastic Stable Intramedullary Nail Fixation for Paediatric Distal Radius Diaphyseal Metaphyseal Junction Fractures: A New Operative Approach
Publication date: Available online 6 January 2019
Source: Injury
Author(s): Mengmeng Du, Jiuhui Han
Abstract
Background and purpose
The treatment of paediatric distal radius diaphyseal metaphyseal junction (DRDMJ) fractures is a challenge. The purpose of this study was to introduce a new operative approach at the proximal "safe zone" of the posterior interosseous nerve (PIN) to treat paediatric DRDMJ fractures and analyse the safety and efficacy of antegrade elastic stable intramedullary nail (ESIN) fixation.
Methods
Thirty paediatric patients with unstable and displaced DRDMJ fractures were treated by antegrade ESIN fixation from November 2015 to September 2017. We created the entrance site at the posterolateral side of the proximal radius and 2˜4 cm distal to the articular surface of the radius, using the ESIN to immobilise the fractures. In the study, we reviewed patient demographics, complications, time until removal, and intraoperative time for hardware removal.
Results
Complete fracture healing was achieved between 6 and 12 weeks after surgery. Except for 3 patients presenting with irritation of the skin, we did not observe any complications. Radiologically, no secondary displacement, nail migration, loss of fixation, consolidation delay, non-union, or refracture was noted.
Conclusions
The antegrade ESIN fixation is a minimally invasive, easy-to-learn, alternative operative method to treat paediatric DRDMJ fractures.
Level of Evidence
Therapeutic Level IV
http://bit.ly/2GVuUIM
Plant Diversity and Ethnoveterinary Practices of Ethiopia: A Systematic Review
The systematic review was conducted on Ethnoveterinary Medicinal (EVM) plants from the two (integrated and pastoral) majorly known livestock production systems (LPS) of Ethiopia. A total of 48 documents pertinent to EVM significance were assessed from different sources using Google search engine and local university websites. Search outputs were screened using the developed inclusion criteria, and only 26 documents were selected. Descriptive analysis measures, Document Consensus Factor (DCF), and rank of the collected data were analysed using SPSS version 20 and Microsoft Excel. The result showed that females (33%), being below 40 years of age (27%), and educational level of above college (1%) healers participation was not significance. A total of 645 EVM plant species (from 133 families) were identified. Only 22 (16.54%) plant families were represented by one species. Leaf (47.8%) was the major plant part used to prepare remedies. The major administration route was oral route (58.2%). Blackleg 43 (0.188), diarrhea 25 (0.110), and wound 18 (0.079) were the most commonly treated livestock ailments. Solanaceae and Fabaceae were the frequently utilized EVM plant families in integrated and pastoral LPS, respectively. Croton macrostachyus (Bisana) and Solanum incanum (Embuay) were the most widely applied EVM plant species in integrated and pastoral LPS, respectively. Pastoral LPS were using higher number of specific EVM plants (DCF>0.5) compared to integrated LPS. Less than 40% (n
http://bit.ly/2GYkjNb
Natural Killer Response and Lipo-Metabolic Profile in Adults with Low HDL-Cholesterol and Mild Hypercholesterolemia: Beneficial Effects of Artichoke Leaf Extract Supplementation
The aim of the present study is to evaluate the effects of 60-day artichoke leaf extract (ALE) supplementation (250mg, twice daily) on cytokines levels, natural killer cell (NK) response, and lipo-metabolic profile (HDL, LDL, and total-cholesterol, triglycerides (TG), ApoB, ApoA, lipid accumulation product (LAP), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)) in twenty adults (9/11 males/females, age=49.10 ± 13.74 years, and BMI=33.12 ± 5.14 kg/m2) with low HDL-C and mild hypercholesterolemia. Hierarchical generalized linear model, adjusted for sex, BMI, and age, has been used to evaluate pre-post treatment changes. A significant increase for HDL-C (β=0.14, p=0.0008) and MCP-1 (β=144.77, p=0.004) and a significant decrease for ApoB/ApoA (β=-0.07, p=0.03), total-C/HDL-C ratio (β=-0.58, p
http://bit.ly/2Rzj9vB
Chromatography Based Metabolomics and In Silico Screening of Gymnema sylvestre Leaf Extract for Its Antidiabetic Potential
Gymnema sylvestre, popularly known as gurmar, is extensively used in traditional systems of medicine for diabetes, stomach ailments, liver diseases, and cardiac disorders. Dried leaf powder of G. sylvestre was extracted through soxhlation using 70% (v/v) alcohol. The hydroalcoholic extract was concentrated to 1/4th of its volume and basified to isolate gymnemic acid enriched extract using chloroform. The isolated extract was checked for its antioxidant potential against 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), which showed scavenging activity of 82.31% at 80 μg/mL of extract. Quality control analysis of the extract was carried out by TLC. Chloroform and methanol (9.5:0.5, v/v) were used as a solvent system and separated compounds were detected at 254 and 366 nm. A total of 13 metabolites were separated. However, major peaks were at 0.12, 0.69, 0.79, and 0.85. Further, UPLC-MS fingerprinting of the extract was done using acetonitrile and 0.5% formic acid in water as mobile phase in gradient elution mode. A total of 21 metabolites were separated and tentatively identified from the database. Deacyl gymnemic acid and quercetin are the two major metabolites found in the extract. Gymnemic acid, deacyl gymnemic acid, and quercetin were docked with ten different proteins associated with glucose metabolism, transport, and glucose utilization. It has been observed that gymnemic acid was more potent than deacyl gymnemic acid in terms of binding affinity towards proteins and showed a favorable interaction with amino acid residues at the active site. Thus, the present study gives an insight of identified metabolites with protein interaction and a reason for the hypoglycemic potential of deacyl gymnemic acid enriched extract, which can be further explored for in vitro and in vivo studies to establish its phytopharmacological and therapeutic effect.
http://bit.ly/2GZRYGa
Antihypertensive Activity of Leersia hexandra Sw. (Poaceae) Aqueous Extract on Ethanol-Induced Hypertension in Wistar Rat
Leersia hexandra (L. hexandra) is used in traditional medicine to treat many diseases including hypertension. This study aimed to evaluate the curative effects of the aqueous extract of L. hexandra on hypertension. Hypertension was induced in rats by oral administration of ethanol (5 g/kg/day) for five weeks. The animals were divided into 2 groups: one group of 5 rats receiving distilled water (10 mL/kg) and another group of 20 rats receiving ethanol. At the end of the 5 weeks of administration of ethanol, the animals were divided into 4 groups of 5 rats each: one group of hypertensive rats receiving distilled water (10 mL/kg), another one receiving nifedipine (10 mg/kg), and two groups of hypertensive rats receiving L. hexandra at doses of 100 and 200 mg/kg, respectively. The results showed that ethanol induced a significant increase in the mean arterial pressure (MAP) and heart rate of normotensive rats. The administration of the extract (100 and 200 mg/kg) or nifedipine caused a significant decrease of MAP compared to hypertensive rats. Ethanol induced a significant increase of lipid profile, the atherogenic index, creatinine, and transaminase activities. Ethanol also induced a significant decrease in serum HDL-cholesterol and antioxidant markers evaluated. Treatment of hypertensive rats with L. hexandra or nifedipine significantly improved lipid profile, hepatic and renal functions, and antioxidant status. The curative effect of L. hexandra extract on hypertension is probably related to its antihypertensive, hypolipidemic, and antioxidant activities, which justifies its empirical use in the treatment of hypertension.
http://bit.ly/2FbCI6x
Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A
Background. As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered. Objective. To identify the potential therapeutic targets of biochanin A in treating osteosarcoma. Methods. In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A. Results. Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A. Conclusion. Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma.
http://bit.ly/2FamUl9
Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study
Lappaconitine is extracted from Aconitum sinomontanum Nakai, which belongs to the Ranunculaceae. Lappaconitine is as a diterpenoid alkaloid used as a nonaddictive analgesic. To assure the rational use of the drug, ultrahigh-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was conducted to determine lappaconitine in mouse blood and its application to pharmacokinetics. In this study, khasianine was used as internet standard (IS). A UPLC BEH C18 column was used for chromatographic separation and the mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid). The flow rate of was 0.4 mL/min. Quantitative detection was performed in a multiple reaction monitoring (MRM) mode using an electrospray ionization source in positive mode. Twenty-four mice were randomly divided into four groups, three of which received 2, 4, and 8 mg/kg lappaconitine by intragastric administration, while the other group received 1 mg/kg lappaconitine by intravenous administration. After 0.0833, 0.5, 1, 1.5, 2, 3, 4, and 8 h, blood samples were collected and acetonitrile was used for protein precipitation. A linear calibration relationship (R2 = 0.9979) in the range of 0.1-500 ng/mL in mouse blood indicated good results. The lower limit of quantitation was 0.1 ng/mL and the limit of detection was 0.04 ng/mL. The intra-day and inter-day precision were below 13% and 14%, respectively. The accuracy was 90.1-107.2%, and the recovery exceeded 81.1%. The matrix effect ranged between 102.1 and 108.8%. The absolute bioavailability of lappaconitine was 2.0%. UPLC-MS/MS achieved high sensitivity, speed, and selectivity. Methodological verification indicated this method as suitable for determination of lappaconitine in mouse blood.
http://bit.ly/2GUjzsg
Middle Ear Transducer: Long Term Stability of the Latest Generation T2
Objectives/Hypothesis. Comparing long term stability of the Middle Ear Transducers (MET) of the 1st generation T1 (Otologics LLC) with the current generation T2 (Cochlear Ltd.) in all our clinical cases with standard incus coupling. Study Design. Retrospective chart review. Methods. 52 ears implanted with a MET device between 2008 and 2016 were analyzed retrospectively. All patients suffered from sensorineural hearing loss and the actuator was coupled to the body of the incus (standard coupling). 23 ears were implanted with the transducer T1 (Otologics LLC) between 2008 and 2011 and 29 ears were implanted with the current transducer T2 since 2011 (Otologics LLC/Cochlear Ltd.). Latest available in situ and bone conduction (BC) thresholds were exploited for a follow-up period of up to 7 years after first fitting. Long term stability of coupling and actuator performance was evaluated by tracking differences between in situ and BC thresholds. Results. In the T1 group, 9 out of 23 implants were still used by the patients at their last follow-up visit (average observation time 3.7 yrs.; min 1.0 yrs., max 7.4 yrs.). In 9 patients a technical failure identified by a decrease of in situ threshold of more than 15 dB compared to BC thresholds [Δ (in situ – BC)] lead to non-usage of the implant and 7 explantations. Five other explantations occurred due to medical reasons such as BC threshold decrease, infection, or insufficient speech intelligibility with the device. In the T2 group, 23 out of 29 implants were still used at the most current follow-up visit (average observation time 3.3 yrs.; min 1.0 yrs., max 4.8 yrs.). No technical failures were observed up to more than 4 years after implantation. Five T2 patients discontinued using the device due to insufficient benefit; two of these patients were explanted. One patient had to be explanted before the activation of the device due to disorders of wound healing. Nevertheless, a small but significant decrease of hearing loss corrected coupling efficiency [Δ (in situ – BC)] was seen in the T2 group. Conclusions. In contrast to the T1 transducers of the earlier generation of MET systems where technical failures occurred frequently, no technical failures were detected after 29 implantations with the current T2 transducers. However, a small but significant decline of transmission efficiency was observable even in the T2 implanted group.
http://bit.ly/2RxuA6R
Splenectomy Promotes Macrophage Polarization in a Mouse Model of Concanavalin A- (ConA-) Induced Liver Fibrosis
Background. Splenectomy can improve liver function and survival in patients with autoimmune hepatitis (AIH) and liver cirrhosis. We investigated the underlying mechanism in a mouse model of concanavalin A- (ConA-) induced liver fibrosis. Methods. We used ConA to induce immune liver fibrosis in BALB/c mice. Splenectomy was performed alone or with the administration of dexamethasone (DEX). Changes in blood and liver tissues were evaluated. Results. Mice treated with ConA for 7 weeks developed advanced liver fibrosis, while splenectomy suppressed liver fibrosis. Although the populations of macrophages/monocytes and M1 macrophages decreased after splenectomy, the inflammatory factors associated with M2 macrophages increased after splenectomy. Furthermore, the population of circulating myeloid-derived suppressor cells (MDSCs) increased after splenectomy. After ConA treatment, elevated levels of activated and total NF-kBp65/p50 combined with DNA were observed in hepatic tissues. In contrast, the levels of NF-κB p65/p50 decreased after splenectomy. Conclusions. Splenectomy may promote the polarization of MDSCs and the differentiation of M2 macrophages while restricting the level of NF-κB p65-p50 heterodimers. These factors may suppress the progression of liver fibrosis.
http://bit.ly/2H6o1o6
Human Biology
| Health care: Where are we heading? Monali Amit Shah Advances in Human Biology 2019 9(1):1-1 |
| The incidence of brain tumours in Iran: A systematic review and meta-analysis Soheil Hassanipour, Gholamreza Namvar, Mohammad Fathalipour, Mohammad Ghorbani, Elham Abdzadeh, Saber Zafarshamspour, Shirin Riahi, Abdollah Mohammadian-Hafshejani, Hamid Salehiniya Advances in Human Biology 2019 9(1):2-7 Background: Brain tumours (BTs) constitute approximately 88% of all central nervous system tumours. The present study aimed to determine the age-standardised rate (ASR) of BTs in Iran. Methods: A comprehensive search was conducted on all studies of BTs incidence using Medline/PubMed, Scopus, Embase, Google Scholar and Web of Sciences as international databases and Scientific Information Database, MagIran, IranMedex and IranDoc as Iranian databases until April 2018. This systematic review was done based on the preferred reporting items for systematic reviews and meta-analyses. Results: The primary search yielded 312 relevant studies. A total of 17 studies were included after more detailed retrieval. The results of the random-effect model were demonstrated the ASR of BTs was 4.16 (95% confidence interval [CI], 3.20–5.12) for males and 3.40 (95% CI, 2.67–4.13) for females. Conclusion: The incidence of BTs is lower in Iran compared to other parts of the world. The incidence of nervous system cancers is increasing base on region, geographical, and economic conditions in Iran. Hence, training programmes can be considered to reduce the risk factors, complications of nervous system cancers and early diagnosis of nervous tumors. |
| The effect of placenta abruption on the risk of intrauterine growth restriction: A meta-analysis Ensiyeh Jenabi, Salman Khazaei, Bita Fereidooni Advances in Human Biology 2019 9(1):8-11 There is a contradict findings on the effect of placenta abruption on the risk of intrauterine growth restriction (IUGR). Therefore, the objective of present meta-analysis was to identify all the eligible studies to assess the effect of placenta abruption on the risk of IUGR. The major electronic databases, including PubMed, Scopus and Web of Science, were searched to identify relevant published studies. The literature search included 551 articles until January 2018 with 35,201 participants. In the end, a total of seven references were remained for this meta-analysis. Two independent authors reviewed the retrieved the studies and extracted data. I2 statistics was used to assess of heterogeneity. The random effects model was conducted to assess pooled effects size. the results of study showed that placenta abruption has a significant effect on the risk of IUGR based on odds ratio results (2.06; 95% confidence interval: 1.57, 2.55). The result reported of the measure of effect was homogeneous (I2 = 0.0%). we presented based on reports in epidemiological studies that placenta abruption is a risk factor for IUGR. |
| Is breech presentation associated with autism spectrum disorders among children: A meta-analysis Ensiyeh Jenabi, Saeid Bashirian, Salman Khazaei Advances in Human Biology 2019 9(1):12-15 The meta-analysis of case–control and cohort studies was conducted to obtain the association between breech presentation and the risk of autism spectrum disorder (ASD) among children. The search for relevant studies in major electronic databases was performed including; Web of Science, PubMed and Scopus up to May 2018. The odds ratio (ORs) with 95% confidence intervals (CI) was extracted from eligible studies. The pooled estimate of OR was not indicated a significant association between breech presentation and risk of ASD among children (OR = 1.15, 95% CI = 0.93–1.37), but this association was significant in the unadjusted analysis (OR = 1.32, 95% CI = 1.05–1.58). Our findings were not showed that breech presentation is associated with increased risk of ASD among children. |
| The incidence of testicular cancer in Iran from 1996 to 2017: A systematic review and meta-analysis Soheil Hassanipour, Mohammad Ghorbani, Milad Derakhshan, Hamed Fouladseresht, Shokrollah Mohseni, Elham Abdzadeh, Shirin Riahi, Morteza Arab-Zozani, Hamed Delam, Hamid Salehiniya Advances in Human Biology 2019 9(1):16-20 Objective: Testicular cancer (TC), although it is one of the most unusual cancers, seems to be increasing. There is no accurate information on the incidence of this cancer in Iran. The present study is conducted to evaluate the incidence rates of TC in Iran. Methods: A systematic search was conducted on all published studies of TC incidence using Medline/PubMed, Scopus, Embase, Web of Science, Google Scholar and four Iranian databases (Scientific Information Database, MagIran, IranMedex and IranDoc) until June 2018. This systematic review was done according to the preferred reporting items for systematic reviews and meta-analyses. Result: The database searching yielded 132 potentially relevant studies. A total of 11 studies were included in the study. The results of the random-effects model were demonstrated that the age-standardised rate (ASR) of TC was 1.13, 95% confidence interval (0.97–1.29) among Iranian males. Conclusion: ASR for TC in Iran is lower than the world average; however, it has a higher incidence than other Asian countries. |
| Effect of cryopreservation on the structural and functional integrity of human periodontal ligament stem cells: A systematic review Rujuta Krishnakant Pandya, Monali Shah, Yesha Shroff, Mrugank Vyas Advances in Human Biology 2019 9(1):21-27 Aim: The aim of the present systematic review was to assess the effect of cryopreservation on the human periodontal ligament (PDL) stem cells and their ability for periodontal regeneration. Materials and Methods: An electronic search without time restrictions was conducted up to August 2017 in indexed databases using the combination of different keywords including cryopreservation, cryofixation, vitrification and human periodontal ligament stem cells. The exclusion criteria included reviews, commentaries, letters to the editor, interviews and updates. The relevant articles were included and data extraction was processed. Results: Dimethyl sulphoxide was used as a cryoprotectant in all the studies which yielded good results. The magnetic freezing proves to be better than the normal freezer. The cryopreserved cells showed no significant difference for viability, proliferation, and regenerative capacities as compared to the fresh human PDL stem cells (PDLSCs), in vitro as well as in vivo. Conclusion: Cryopreservation of the human PDLSCs would serve as an opportunity for future regenerative therapy for the periodontium. |
| The effect of diabetes on nerve–muscle conduction of tibial and peroneal nerve association with habit and habitat in Bikaner Region Ekta Soni, Priyanka Soni, Jitendra Kumar Acharya Advances in Human Biology 2019 9(1):28-31 Introduction: Diabetes is due to defect in Beta cell of islets of Langerhans, that is seen in pancreas. This defect is responsible for disturbance in blood glucose level. Other factors which are also responsible includes diet, hereditary, immunological factor, lack of exercise etc., The damage to nerves in DM has been assumed to be a result of the interaction of metabolic defects complicated by vasa nervorum abnormalities. Nerve conduction velocity, are standard measurement used to confirm the presence or absence of diabetic neuropathy. In Nerve conduction velocity study common nerves that are studied are common peroneal nerve, tibial nerve and sural nerve. Materials and Methods: The study was planned in Physiology Department in close collaboration with Department of Medicine (Diabetic Section), S.p.mc. Bikaner. A total of 100 subjects for study from diabetic centre, were selected. Institutional ethical clearance was taken before commencement of study from ethical committee of our institution. Results: In present study, maximum number of patients were non-smokers in both study and control groups (87% and 91% respectively) and this difference was found statistically insignificant (P > 0.05). We observed that the patients were vegetarian in both study and control groups and this difference was found statistically insignificant (P > 0.05). The mean peroneal nerve in study group was 42.26 ± 1.95 m/s and in control group it was 52.05 ± 4.78 m/s and the difference was found statistically highly significant (P < 0.001) and mean value of tibial nerve in study group was 41.71 ± 2.29 m/s and in control group it was 49.84 ± 2.67 m/s and the difference was found statistically highly significant (P < 0.001). Conclusion: In our study, we concluded that nerve conduction velocities decreases in tibial and common peroneal nerve in diabetic patients as compared to control. Nerve conduction velocities also decrease with increasing age, increased HbA1C >6.5%. |
| New insight into the role of electronic apex locators in detecting simulated horizontal root fractures: An In vitro study Mukti M Shah, Vaishali V Parekh, Nidhi J Patel, Parth V Dodiya, Dipak H Chauhan Advances in Human Biology 2019 9(1):32-36 Aim and Objectives: The aim of this study is to check the accuracy of two different electronic apex locators (EALs): Canal Pro and Root ZX – in locating simulated horizontal root fractures (HRFs). Materials and Methods: Forty-five recently extracted, single-rooted, human permanent teeth were selected for the study. Endodontic access cavity was prepared, and canal patency was checked using no. 10-K file. Horizontal fractures were simulated using 0.2-mm thick diamond disk in coronal, middle and/or apical third of root by operator one, until half of the canal was exposed circumferentially. Using both the apex locators, all the fractures were detected by the second operator to confirm the accuracy of EALs. The actual length of the fractures was then measured under ×2.5 magnification, and results were subjected to statistical analysis. Results: Results were analysed using the one-way analysis of variance and Tukey's post hoc test, and the differences between all the test samples were analysed. All the measurements were compared to the actual values separately. A statistically significant difference was determined at 95% confidence level (P ≤ 0.05). Conclusion: Investigated both the EAL are capable of detecting simulated HRF and that the Canal Pro showed a higher accuracy rate. |
| To determine the prevalence of glucose-6-phosphate dehydrogenase deficiency using a novel water-soluble tetrazolium-8 formazan method' for neonatal screening in region of Himachal Pradesh, India Seema Sharma, Milap Sharma Advances in Human Biology 2019 9(1):37-41 Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most significant enzyme defect in India with an incidence ranging from 2% to 27.9% in different communities. Prolonged neonatal jaundice and haemolytic crisis are known to occur in children with G6PD deficiency. Hence, screening of a population for G6PD deficiency is paramount. A Novel water soluble tetrazolium-8 (WST-8) Formazan Method has been used in this study for in-field mass-screening of G6PD in the region of Himachal Pradesh, India. Materials and Methods: In this prospective study, 5652 neonates were screened to assay G6PD activity using WST8/1-methoxy phenazine methosulphate method within the first 48 h of life. Orange colour at the end of the procedure indicated normal G6PD activity while pink or colourless appearance indicated G6PD deficiency. Results: After the screening of 5652 neonates, the prevalence of G6PD deficiency was 12.4%. 45 newborns (6%) had a severe G6PD deficiency. Males were more affected than females (70:30). Furthermore, males had higher prevalence of deficiency than females (64% [n = 29] and 16% [n = 16]). Conclusions: G6PD deficiency assessment by the method used for population screening in the study was easy to do and quite simple. Following this, the high prevalence of this deficiency was noted in Himachal Pradesh. This study highlights the need to do neonatal screening of G6PD deficiency in population so that untowards complications like haemolytic crisis, complications due to neonatal jaundice can be avoided. |
| Evaluation of the accessible level of iodine in marketed iodised salt in Iran: A comparison with standard recommended values Abolfazl Mohammadbeigi, Ali Salehi, Hamidreza Heidari, Mahdi Asadi-Ghalhari Advances in Human Biology 2019 9(1):42-45 Background: Iodine is one of the essential micronutrients for synthesise and secrete adequate amounts of thyroid gland hormones. Its deficiency is the most important threatening causes for human health. The aim of this study was to evaluate iodine concentration in marketed edible salt samples in Qom city and to compare with existing standards and offering solutions necessary to fix the probably problems. Materials and Methods: A cross-sectional, descriptive study was carried out on 60 samples of 20 brands of marketed edible salt in Qom during 2017. Iodine concentration was evaluated by the British Pharmacopoeia titration method. Results: According to the national standard of Iran during this study, iodine concentration in 51.67% of salt samples was in acceptable limits and 48.33% of samples were out of acceptable ranges. None of the tested samples had iodine content more than the standard limit. Conclusions: To improve salt fortification status and removing iodine deficiency in society, the following actions should be considered: enforcing producers to follow national and international standards, continuous monitoring the producers, necessary legal actions against offending manufacturers and appropriate measures by health ministry and relevant authorities. |
Pediatric Neuropsychology
| Review of Neurodevelopmental Disorders in Children and Adolescents |
Investigating the BRIEF and BRIEF-SR in Adolescents with Mild Traumatic Brain InjuryAbstractTo date, limited research has investigated the Behavioral Rating Inventory of Executive Function (BRIEF) and BRIEF Self-Report (BRIEF-SR) in adolescents presenting exclusively with mild traumatic brain injuries (mTBI). The present study was retrospective and included 163 adolescents (43% male; M age = 14.80; M days since injury = 34.10) referred for neuropsychological evaluation after mTBI. Results revealed that mean BRIEF and BRIEF-SR clinical scale scores in the sample were generally similar to those in the standardization sample, commensurate with previous literature on the trajectory of cognitive and symptom recovery after mTBI. Adolescents reported significantly higher scores than their parents only on Emotional Control, with no differences emerging on other clinical scales. Confirmatory factor analyses indicated that the two-factor model of the BRIEF-SR (Metacognition and Behavioral Regulation; Comparative Fit Index (CFI) = 0.97) provided relatively and statistically significant better fit than a one-factor model extracted in exploratory analyses. Results also indicated that a three-factor model of the BRIEF capturing Metacognition, Behavioral Regulation, and Emotional Regulation (CFI = 0.98) provided relatively and significantly better fit than the two-factor model. These results suggested that adolescents in the post-acute phase of mTBI recovery may rate their own executive dysfunction in terms of metacognitive and behavioral difficulties, while their parents may observe executive dysfunction in these two dimensions in addition to emotional dysfunction. Relationships to previous literature, limitations of the present study, and implications for clinical practice are discussed. |
| Test and Book Reviews in Pediatric Neuropsychology |
| Correction to: Automatized Sequences as a Performance Validity Test? Difficult If You Have Never Learned Your ABCs In the original article the name of author Allyson G. Harrison was misspelled. The original article has been updated and her name is correct here. |
| Pediatric Performance Validity Testing: State of the Field and Current Research |
One-Minute PVT: Further Evidence for the Utility of the California Verbal Learning Test—Children's Version Forced Choice Recognition TrialAbstractObjectiveTo replicate previous research on the forced choice recognition trial for the California Verbal Learning Test—Children's Version (FCR-C). MethodClassification accuracy of the FCR-C was computed in 178 children referred for neuropsychological assessment to a tertiary care hospital. ResultsFCR-C ≤ 14 produced the best combination of sensitivity (.12–.42) and specificity (.88–.96). Unlike some of the criterion performance validity tests (PVTs), base rate of failure on the FCR-C was evenly distributed across age ranges. ConclusionThe FCR-C is a quick and inexpensive PVT, unaffected by cognitive maturation, and highly specific to psychometrically defined invalid performance. |
Automatized Sequences as a Performance Validity Test? Difficult If You Have Never Learned Your ABCsAbstractAccurate identification of symptom exaggeration is essential when determining whether or not data obtained in pediatric evaluations are valid or interpretable. Apart from using freestanding performance validity tests (PVTs), many researchers encourage use of embedded measures of test-related motivation, including the newly developed automatized sequences test (AST). Such embedded measures are based on identification of performance patterns that are implausible if the test taker is investing full effort; however, it is unclear whether or not persons with pre-existing cognitive difficulties such as specific learning disabilities (SLD) might be falsely accused of poor test motivation due to actual but impaired learning of basic sequences. This study examined the specificity of the AST by reviewing performance of 83 SLD adolescents. Anywhere from 22 to 41% of SLD adolescents investing good effort failed one or more of the tasks included in the AST, and those with lower intelligence scores had higher rates of failure. Clinicians should therefore be cautious if using this PVT with individuals who have a documented history of reading, learning, or intellectual problems. |
Detecting Invalid Performance in Youth with Traumatic Brain Injury Using the Child and Adolescent Memory Profile (ChAMP) Lists SubtestAbstractBackgroundNeuropsychological assessment must include determinants of validity. This study sought to develop an embedded performance validity indicator for the Child and Adolescent Memory Profile (ChAMP) Lists verbal memory subtest. MethodsChildren and adolescents (N = 103; mean age = 14.6 years, SD = 2.4, range = 8–18) who were on average 25 weeks (SD = 15.1) post-traumatic brain injury (TBI; 85% mild and 15% moderate-severe) were administered ChAMP Lists and two stand-alone performance validity tests (PVTs; Test of Memory Malingering; Medical Symptom Validity Test). Nineteen patients were deemed to have invalid performance defined as failure on both PVTs. Binary logistic regression and classification statistics were used to determine a cutoff score for invalid performance on ChAMP Lists using failure on two PVTs as the criterion. ResultsInvalid performance was not associated with demographics, injury type, or time since injury, but was significantly correlated with ChAMP Lists scaled scores. Only ChAMP Lists Recognition predicted validity grouping and had excellent discrimination (area under the curve of 93%). A cutoff scaled score of 7 or less on ChAMP Lists Recognition achieved sensitivity for invalid performance at 79% while maintaining specificity at 91%. A more stringent cutoff score of 5 or less on ChAMP Lists Recognition achieved sensitivity for invalid performance at 63% with specificity at 95%. ConclusionThis study yields a promising embedded performance validity indicator for ChAMP Lists Recognition with good sensitivity and excellent specificity for detecting invalid performance in youth with TBI. |
Why Children Fail the Test of Memory Malingering: Review of False Positive Performance in Pediatric StudiesAbstractRationaleThe Test of Memory Malingering (TOMM) is a commonly utilized performance validity test currently recommended for pediatric use with children as young as 5 years of age. Yet, a small sample of children struggles to pass the TOMM due to true cognitive difficulties. The systematic search and review identified the reported cases of false positive and overall failing TOMM performance in children. The goal of this project was to increase the understanding of the cognitive constructs and minimum cognitive abilities necessary for children to pass the TOMM. The secondary goal was to use the existing data to suggest clinical guidelines related to use of the TOMM with children. Methods and ResultsA comprehensive search of PubMed/MEDLINE, EMBASE, Web of Science, and PsycINFO was conducted, returning an initial 12,052 results. After duplicate articles were removed, 10,583 remained; 61 were evaluated for eligibility and 22 were included as our final sample. Results suggested that false positives were observed in children with low IQ, memory issues, complex medical presentation, and younger children. ConclusionsWithout relevant, quality validation and normative studies, the TOMM should not be used clinically with young children or children suspected of having significant cognitive issues. Failing performance on the TOMM does not necessarily indicate poor effort or invalidate the neuropsychological profile. Instead, it may be reflective of other factors, particularly in children below age 6, children with lower intellectual abilities (especially FSIQ ≤ 75), children with multiple diagnoses, or children with more severe neurological diagnoses. Clinical recommendations are also discussed. |
The Rey-Osterrieth Complex Figure: a Useful Measure of Organizational Skills for Adolescents with ADHD?AbstractDeficits in organization, time management, and planning (OTMP) abilities are common in adolescents with attention-deficit/hyperactivity disorder (ADHD) and contribute to impairment. Assessment of these skills is vital, but few measures have been validated for youth with ADHD. The Rey-Osterrieth Complex Figure (ROCF) task is frequently used in research and clinical settings despite limited validity evidence. The present study evaluated whether ROCF performance, as scored via the Boston Qualitative Scoring System, exhibited validity as a measure of OTMP skills in a large (N = 285) sample of adolescents comprehensively diagnosed with ADHD. ROCF performance exhibited minimal associations with measures of OTMP, executive functioning, or aspects of academic impairment affected by OTMP abilities; all correlations were nonsignificant after accounting for the influence of intelligence. Further, ROCF task performance did not differ by ADHD presentation or medication status. Correlations with other variables that may be confounded with ROCF performance (anxiety symptoms, depressive symptoms, parent education) also demonstrated nonsignificant correlations with all BQSS scores. The ROCF may not adequately capture OTMP abilities of adolescents with ADHD; future directions for the assessment of OTMP skills are discussed. |
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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