bluuebunny/crossref_metadata_2025 huggingface dataset:
ROR2 induces cell apoptosis via activating IRE1α/JNK/CHOP pathway in high-grade serous ovarian carcinoma in vitro and in vivo
Authors: Li Rui , Liu Tianfeng , Shi Juanjuan , Luan Wenqing , Wei Xuan , Yu Jiangtao , Mao Hongluan , Liu Peishu
Published: December 2019

Background

Epithelial ovarian cancer (EOC) is the most lethal cancer in female genital tumors. New disease markers and novel therapeutic strategies are urgent to identify considering the current status of treatment. Receptor tyrosine kinases family plays critical roles in embryo development and disease progression. However, ambivalent research conclusions of ROR2 make its role in tumor confused and the underlying mechanism is far from being understood. In this study, we sought to clarify the effects of ROR2 on high-grade serous ovarian carcinoma (HGSOC) cells and reveal the mechanism.

Methods

Immunohistochemistry assay and western-blot assay were used to detect proteins expression. ROR2 overexpression adenovirus and Lentivirus were used to create ROR2 overexpression model in vitro and in vivo, respectively. MTT assay, colony formation assay and transwell assay were used to measure the proliferation, invasion and migration ability of cancer cells. Flow cytometry assay was used to detect cell apoptosis rate. Whole transcriptome analysis was used to explore the differentially expressed genes between ROR2 overexpression group and negative control group. SiRNA targeted IRE1α was used to knockdown IRE1α. Kira6 was used to inhibit phosphorylation of IRE1α.

Results

Expression of ROR2 was significantly lower in HGSOC tissues compared to normal fallopian tube epithelium or ovarian surface epithelium tissues. In HGSOC cohort, patients with advanced stages or positive lymph nodes were prone to express lower ROR2. Overexpression of ROR2 could repress the proliferation of HGSOC cells and induce cell apoptosis. RNA sequencing analysis indicated that ROR2 overexpression could induce unfold protein response. The results were also confirmed by upregulation of BIP and phosphorylated IRE1α. Furthermore, pro-death factors like CHOP, phosphorylated JNK and phosphorylated c-Jun were also upregulated. IRE1α knockdown or Kira6 treatment could reverse the apoptosis induced by ROR2 overexpression. Finally, tumor xenograft experiment showed ROR2 overexpression could significantly repress the growth rate and volume of transplanted tumors.

Conclusions

Taken together, ROR2 downregulation was associated with HGSOC development and progression. ROR2 overexpression could repress cell proliferation and induce cell apoptosis in HGSOC cells. And the underlying mechanism might be the activation of IRE1α/JNK/CHOP pathway induced by ROR2.
Rates of periprosthetic infection and surgical revision in Beijing (China) between 2014 and 2016: a retrospective multicenter cross-sectional study
Authors: Peng Hui-ming , Wang Long-chao , Cheng Ji-ying , Zhou Yi-xin , Tian Hua , Lin Jian-hao , Guo Wan-shou , Lin Yuan , Qu Tie-bing , Guo Ai , Cao Yong-ping , Weng Xi-sheng
Published: December 2019

Background

Periprosthetic joint infection (PJI) is a rare but devastating complication after total joint arthroplasty. There is a paucity of data on the incidence and prevalence of periprosthetic infection in mainland China. This study aimed to analyze the rates of surgical revision after arthroplasty due to PJI and the procedures followed in Beijing, China.

Methods

The study involved a retrospective multicenter cross-sectional survey of patients undergoing revisions for periprosthetic infection after hip/knee arthroplasty at nine hospitals in Beijing from 2014 to 2016. Age, gender, body mass index, primary diagnosis, comorbidity, primary surgery, treatment methods, and post-revision complications were analyzed.

Results

A total of 38,319 hip/knee arthroplasties and 366 (0.96%) revisions for PJI were identified. Of these, 161 (161/14,110; 1.14%) revisions involved hip arthroplasty, whereas 205 (205/24,209; 0.85%) revisions were due to knee arthroplasty. Procedures for revisions of infected hip included 7 (4.3%) cases of open debridement and prosthesis retention, 32 (19.9%) cases of one-stage exchange, 121 (75.2%) cases of two-stage exchange, and 1 (0.007%) case of hip dissection. As for the infected knee, the procedures included 45 (22.0%) cases of open debridement and prosthesis retention, 13 (6.3%) cases of one-stage exchange, 143 (69.8%) cases of two-stage exchange, and 4 (0.02%) cases of knee fusion.

Conclusions

The study found the rates of revision due to PJI to be low. Nonetheless, the incidence of PJI in mainland China could be higher and calls for more elaborate studies in geographically and socioeconomically diverse health institutions.
ROCK2 deprivation leads to the inhibition of tumor growth and metastatic potential in osteosarcoma cells through the modulation of YAP activity
Authors: Zucchini Cinzia , Manara Maria Cristina , Cristalli Camilla , Carrabotta Marianna , Greco Sara , Pinca Rosa Simona , Ferrari Cristina , Landuzzi Lorena , Pasello Michela , Lollini Pier-Luigi , Gambarotti Marco , Donati Davide Maria , Scotlandi Katia
Published: December 2019

Background

The treatment of metastatic osteosarcoma (OS) remains a challenge for oncologists, and novel therapeutic strategies are urgently needed. An understanding of the pathways that regulate OS dissemination is required for the design of novel treatment approaches. We recently identified Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as a crucial driver of OS cell migration. In this study, we explored the impact of ROCK2 disruption on the metastatic capabilities of OS cells and analyzed its functional relationship with Yes-associated protein-1 (YAP), the main transcriptional mediator of mechanotransduction signaling.

Methods

The effects of ROCK2 depletion on metastasis were studied in NOD Scid gamma (NSG) mice injected with U-2OS cells in which ROCK2 expression had been stably silenced. Functional studies were performed in vitro in human U-2OS cells and in three novel cell lines derived from patient-derived xenografts (PDXs) by using standard methods to evaluate malignancy parameters and signaling transduction. The nuclear immunostaining of YAP and the evaluation of its downstream targets Cysteine Rich Angiogenic Inducer 6, Connective Tissue Growth Factor and Cyclin D1 by quantitative PCR were performed to analyze YAP activity. The effect of the expression and activity of ROCK2 and YAP on tumor progression was analyzed in 175 OS primary tumors.

Results

The silencing of ROCK2 markedly reduced tumor growth and completely abolished the metastatic ability of U-2OS cells. The depletion of ROCK2, either by pharmacological inhibition or silencing, induced a dose- and time-dependent reduction in the nuclear expression and transcriptional activity of YAP. The nuclear expression of YAP was observed in 80/175 (46%) tumor samples and was significantly correlated with worse patient prognosis and a higher likelihood of metastasis and death. The use of verteporfin, a molecule that specifically inhibits the TEAD–YAP association, remarkably impaired the growth and migration of OS cells in vitro. Moreover to inhibiting YAP activity, our findings indicate that verteporfin also affects the ROCK2 protein and its functions.

Conclusions

We describe the functional connection between ROCK2 and YAP in the regulation of OS cell migration and metastasis formation. These data provide support for the use of verteporfin as a possible therapeutic option to prevent OS cell dissemination.
High risk of gastrointestinal hemorrhage in patients with systemic sclerosis
Authors: Lin Yi-Ting , Chuang Yun-Shiuan , Wang Jiunn-Wei , Wu Ping-Hsun
Published: December 2019

Background

Systemic sclerosis (SSc), a life-threatening autoimmune disease characterized by vasculopathy. Numerous SSc patients demonstrate gastrointestinal (GI) involvement but the delicate GI bleeding risk remains sparse. We aimed to explore the role of SSc in determining the long-term risk of GI bleeding, including bleedings of upper (peptic and non-peptic ulcers) and lower GI tracts.

Methods

Patients with SSc diagnosis were identified from the Catastrophic Illness Patient Database and the National Health Insurance Research Database from 1998 to 2007. Each SSc patient was matched with five SSc-free individuals by age, sex, and index date. All individuals (case = 3665, control = 18,325) were followed until the appearance of a GI bleeding event, death, or end of 2008. A subdistribution hazards model was assessed to evaluate the GI bleeding risk with adjustments for age, sex, and time-dependent covariates, comorbidity, and medications.

Results

The incidence rate ratios of GI bleeding were 2.38 (95% confidence interval [CI], 2.02–2.79), 2.06 (95% CI, 1.68–2.53), and 3.16 (95% CI, 2.53–3.96) for over-all, upper, and lower GI bleeding events in SSc patients. In the competing death risk in the subdistribution hazards model with time-covariate adjustment, SSc was an independent risk factor for over-all GI bleeding events (subdistribution hazard ratio [sHR] 2.98, 95% CI, 2.21–4.02), upper GI bleeding events (sHR 2.80, 95% CI, 1.92–4.08), and lower GI bleeding events (sHR 3.93, 95% CI, 2.52–6.13).

Conclusion

SSc patients exhibited a significantly higher risk of over-all and different subtype GI bleeding events compared with the SSc-free population. The prevention strategy is needed for these high GI bleeding risk groups.
Increased urinary volumes in symptomatic Ménière’s Disease
Authors: Di Berardino Federica , Zanetti Diego
Published: December 2019

Objective

The purpose of the research is to test the measurement of the total urinary volume, induced by the diuretic osmotic action of mannitol, in a group of symptomatic MD patients and in healthy controls.

Results

An altered excretory urinary volume after mannitol challenge was observed in symptomatic MD (874.3 ± 302.1) compared to healthy volunteers (361.7 ± 181.6) (p = 0.0001). This easy and self-administered method might be proposed to replace the analysis of the urinary sugars’ concentration in symptomatic MD patients.
Cognitively normal women with Alzheimer’s disease proteinopathy show relative preservation of memory but not of hippocampal volume
Authors: Caldwell Jessica Z. K. , Cummings Jeffrey L. , Banks Sarah J. , Palmqvist Sebastian , Hansson Oskar
Published: December 2019

Background

We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes.

Methods

We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes.

Results

Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau−) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau− CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume.

Conclusions

CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.
Expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease
Authors: Vorsprach Monique , Arens Christoph , Knipping Stephan , Jechorek Dörte , Stegemann-Koniszewski Sabine , Lücke Eva , Schreiber Jens
Published: December 2019

Background

Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance.

Objective

We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ($$\hbox {CysLT}_2$$CysLT2) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, $$n=23$$n=23) as compared to patients with aspirin tolerant asthma (ATA, $$n=17$$n=17) and a control group with nasal polyps, but without asthma (NPwA, $$n=15$$n=15).

Methods

Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing.

Results

We observed a stronger expression of 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and $$\hbox {CysLT}_2$$CysLT2 between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups.

Conclusions

The AA-metabolizing enzymes and the $$\hbox {CysLT}_2$$CysLT2 were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.
The role of 18F-FCH PET/CT in patients with uremic hyperparathyroidism compared with 99mTc-sestaMIBI SPECT/CT and ultrasonography
Authors: Xue Yu , Li Wenbo , Xia Zhu , Lei Chengming , Cao Yiyi , Wang Zhengjie , Pang Hua
Published: December 2019

Background

The aim of this study was to evaluate the diagnostic efficacy of 18F-fluorocholine (18F-FCH) PET/CT for uremic hyperparathyroidism (uHPT) compared to 99mTc-sestaMIBI SPECT/CT and ultrasonography (US).

Methods

A total of 17 uHPT patients with stage 5 chronic kidney disease (CKD) were prospectively enrolled. All patients underwent US, 99mTc-sestaMIBI SPECT/CT, and 18F-FCH within 2 months and received surgical treatment. Visual and quantitative methods were used for image analyses. Intraoperative localization and postoperative histological results of the reference standard as well as the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the three modalities were analyzed using Pearson’s χ2 tests. In addition, the diagnostic efficacy of 18F-FCH PET/CT for uHPT was evaluated. The relationships between PET parameters and laboratory parameters were assessed using the Spearman correlation coefficient.

Results

A total of 63 parathyroid hyperplasia lesions were resected in 17 uHPT patients, and 53 lesions were detected using 18F-FCH PET/CT with no false-positive results. The sensitivity, specificity, accuracy, PPV, and NPV were 84.13%, 100%, 86.49%, 100%, and 52.38%, respectively. In comparison, the corresponding values for 99mTc-sestaMIBI SPECT/CT and US were 63.49%, 90.91%, 67.57%, 97.56%, and 30.30% and 61.90%, 81.82%, 64.86%, 95.12%, and 27.27%, respectively. The volume of hyper-functioning parathyroid glands was significantly different between lesions positive in 18F-FCH PET/CT and negative in 18F-FCH PET/CT (mean volume 1.36 ± 0.55 cm3 vs. 0.83 ± 0.26 cm3; P = 0.019). US misidentified intrathyroidal parathyroid hyperplasia as thyroid nodules in three patients, while 18F-FCH PET correctly identified the anatomy. No significant associations were observed between PET parameters and laboratory parameters in uHPT.

Conclusion

18F-FCH PET/CT was more sensitive and accurate for uHPT than 99mTc-sestaMIBI SPECT/CT and US, and had better preoperative diagnostic efficacy, particularly for lesions diagnosed as a thyroid nodule by US.
Intelligent data cache based on content popularity and user location for Content Centric Networks
Authors: Wu Hsin-Te , Cho Hsin-Hung , Wang Sheng-Jie , Tseng Fan-Hsun
Published: December 2019

Content cache as well as data cache is vital to Content Centric Network (CCN). A sophisticated cache scheme is necessary but unsatisfied currently. Existing content cache scheme wastes router’s cache capacity due to redundant replica data in CCN routers. The paper presents an intelligent data cache scheme, viz content popularity and user location (CPUL) scheme. It tackles the cache problem of CCN routers for pursuing better hit rate and storage utilization. The proposed CPUL scheme not only considers the location where user sends request but also classifies data into popular and normal content with correspond to different cache policies. Simulation results showed that the CPUL scheme yields the highest cache hit rate and the lowest total size of cache data with compared to the original cache scheme in CCN and the Most Popular Content (MPC) scheme. The CPUL scheme is superior to both compared schemes in terms of around 8% to 13% higher hit rate and around 4% to 16% lower cache size. In addition, the CPUL scheme achieves more than 20% and 10% higher cache utilization when the released cache size increases and the categories of requested data increases, respectively.
A tale of lock-free agents: towards Software Transactional Memory in parallel Agent-Based Simulation
Authors: Thaler Jonathan , Siebers Peer-Olaf
Published: December 2019

With the decline of Moore’s law and the ever increasing availability of cheap massively parallel hardware, it becomes more and more important to embrace parallel programming methods to implement Agent-Based Simulations (ABS). This has been acknowledged in the field a while ago and numerous research on distributed parallel ABS exists, focusing primarily on Parallel Discrete Event Simulation as the underlying mechanism. However, these concepts and tools are inherently difficult to master and apply and often an excess in case implementers simply want to parallelise their own, custom agent-based model implementation. However, with the established programming languages in the field, Python, Java and C++, it is not easy to address the complexities of parallel programming due to unrestricted side effects and the intricacies of low-level locking semantics. Therefore, in this paper we propose the use of a lock-free approach to parallel ABS using Software Transactional Memory (STM) in conjunction with the pure functional programming language Haskell, which in combination, removes some of the problems and complexities of parallel implementations in imperative approaches. We present two case studies, in which we compare the performance of lock-based and lock-free STM implementations in two different well known Agent-Based Models, where we investigate both the scaling performance under increasing number of CPU cores and the scaling performance under increasing number of agents. We show that the lock-free STM implementations consistently outperform the lock-based ones and scale much better to increasing number of CPU cores both on local hardware and on Amazon EC. Further, by utilizing the pure functional language Haskell we gain the benefits of immutable data and lack of unrestricted side effects guaranteed at compile-time, making validation easier and leading to increased confidence in the correctness of an implementation, something of fundamental importance and benefit in parallel programming in general and scientific computing like ABS in particular.
Moringa oleifera leaf extract ameliorated high-fat diet-induced obesity, oxidative stress and disrupted metabolic hormones
Authors: Othman Azza I. , Amer Maher A. , Basos Asmaa S. , El-Missiry Mohammed A.
Published: December 2019

Background

Obesity is a health problem in many countries, and maintaining a perfect weight is challenging.Moringa oleiferaleaf extract (ME) is rich in polyphenols with antioxidant and pharmaceutical potential. The present study investigated the potential protective effect ofMoringa oleiferaleaf extract against obesity induced from a high-fat diet (HFD), oxidative stress and disruption of metabolic hormones compared to simvastatin (SIM) or their combination.

Results

Rats fed a HFD for 6 weeks exhibited a significant increase in body weight and levels of serum glucose and lipid fractions, verifying an obesity state. There were also higher levels of insulin and leptin and lower gherlin in sera of HFD rats compared to the levels in control rats. Homeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the atherogenic index were elevated, indicating the development of insulin resistance and dyslipidaemia in these rats. These changes were accompanied with a significant increase in oxidative stress, as indicated by elevated lipid peroxidation and protein oxidation with low levels of antioxidants in liver. The activities of liver function enzymes, including aspartate amino transferase, alanine amino transferase, alkaline phosphatase and gamma glutamyltransferase, were also significantly increased in serum. Concurrent treatment with 300 mg/kg ME for 6 weeks ameliorated the increase in body weight and improved the levels of glucose, lipid fractions and metabolic hormones, indicating the anti-obesity effect and amelioration of tissue insulin resistance potential of ME. ME treatment also normalized oxidative stress and antioxidants in liver and improved liver function enzymes, indicating the antioxidant potential of ME. The effects of ME were similar to SIM, and the combination of these agents was better than each agent alone.

Conclusion

We propose that ME extract has anti-obesity and antioxidant potential and may be used as a lipid-lowering drug to control weight, obesity and its pathophysiological consequences.
Neonatal Crohn’s disease with Oral ulcer as the first symptom caused by a compound heterozygote mutation in IL-10RA: a case report
Authors: Lv Hongyan , Qiao Baojun , Fang Liyuan , Yang Lihong , Wang Qiuli , Wu Sujing , Ren Pengshun , Li Lianxiang
Published: December 2019

Objective

To investigate the clinical and genetic characteristics of neonatal Crohn’s disease (CD), improve recognition of neonatal CD, and reduce the number of patients that are missed or misdiagnosed.

Methods

A 10-day-old Chinese girl with oral ulcers was admitted to the Department of Neonatology. She later developed a rash and perianal disease, but without diarrhea and stool abnormalities. The patient and her parents underwent next-generation sequencing.

Results

The results showed that the patient carries a compound heterozygous mutation in the interleukin-10 receptor A (IL-10RA) (NM_001558.3) gene. One heterozygous mutation was c.301 c > T, P. (Arg 101 Trp) in exon 3 of IL-10RA (a missense mutation), and the other was c. 537G > A, P. (Thr 179 =) in exon 4 of IL 10RA (a synonymous mutation). The patient’s father also carries the c.301 c > T, P. (Arg 101 Trp) heterozygous mutation in exon 3 of IL-10RA, whereas her mother carries the c.537G > A, P. (Thr 179 =) heterozygous mutation in exon 4 of IL-10RA.

Conclusions

The results show that a compound heterozygous mutation in IL-10RA is associated with neonatal CD. Oral ulcers with a rash and perianal disease may be an early symptom of neonatal CD; therefore, such patients should undergo genetic identification as soon as possible.
Impact of conventional insecticides on two bollworms and their indirect effects on the ectoparasitoid, Bracon brevicornis (Wesmael) (Hymenoptera: Braconidae)
Authors: Kandil Mervat A. , Moustafa Hemat Z.
Published: December 2019

Background

Cotton bollworms such as Pectinophora gossypiella and Earias insulana are serious pests which destroy the cotton plant, and Bracon brevicornis is a parasitoid which attacked the larvae of bollworms.

Results

In this study, experiments were performed to investigate and evaluate the toxicity of etofenprox and chlorpyrifos insecticides against newly hatched larvae of Pectinophora gossypiella and Earias insulana. Some biological aspects of compound effects on larval and pupal duration, percentage of mortality, and percentage of adult emergence which resulted from treated newly hatched larvae were studied. The results revealed that LC50 was 0.7 and 0.87 ppm when P. gossypiella was treated with etofenprox and chlorpyrifos, respectively, while LC50 was 0.09 and 0.73 ppm when E. insulana was treated with etofenprox and chlorpyrifos, respectively. The obtained results showed that the percentage of mean larval mortality was 65.0 and 63.0% for treated P. gossypiella, while it was 71.0 and 66.0% for treated E. insulana. The corresponding figure for pupal percentage mortality was 8.0 and 10.0% for treated P. gossypiella, but it was 5.0 and 2.0% for treated E. insulana, with etofenprox and chlorpyrifos, and a prolongation effect in larval and pupal development (total immature stage) resulted from treated both bollworms as follows: 35.5 and 32.4 days for treated P. gossypiella compared with 21.9 days in control and 34.7 and 23.2 days for treated E. insulana compared with 23.1 days in control. The indirect effect of etofenprox and chlorpyrifos on the total immature stage of Bracon brevicornis was 18.2 and 19.5 days compared with 14.3 days in control when B. brevicornis parasitized on P. gossypiella larvae while it was 19.8 and 20.6 days compared with 15.2 days when B. brevicornis parasitized on E. insulana larvae.

Conclusion

The life cycle of B. brevicornis after parasitism on P. gossypiella and E. insulana larvae treated with etofenprox and chlorpyrifos were increased than the control larvae.
The usefulness of diffusion-weighted MRI in the differentiation between focal uterine endometrial soft tissue lesions
Authors: Mansour Tarek Mohamed M. , Ahmed Yasser Abd Al-aal , Ahmed Ghada Abd El-Razik
Published: December 2019

Background

Several endometrial conditions may be challenging for radiologists due to the overlap of imaging features and variable endometrial pathologies. MRI with DWI is the most commonly used imaging technique for the diagnosis and characterization of endometrial focal lesions.

Results

The 50 studied lesions were classified according to their histopathological results into the benign group (28 lesions, 56%) and the malignant group (22 lesions, 44%). Conventional MRI could correctly diagnose 39 of the 50 lesions (22/28 benign and 17/22 malignant lesions), achieving a sensitivity of 77.27%, specificity of 78.56%, accuracy of 78%, predictive positive value (PPV) of 73.91%, and negative positive value (NPV) of 81.48%. By combining DWI and apparent diffusion coefficient (ADC) value mapping at a high b value (b = 1000) in MRI, we could correctly diagnose 47 of the 50 lesions (26/28 benign and 21/22 malignant lesions), with increased sensitivity (95.45%), specificity (92.86%), accuracy (94%), PPV (91.3%), and NPV (96%).

Conclusion

Combining DWI with ADC mapping at a high b value in pelvic MRI examination is valuable in differentiating endometrial focal lesions with increased diagnostic sensitivity, specificity, and accuracy.

Aim of the work

This study aimed to evaluate the role of DWI in the diagnosis and differential diagnosis of benign and malignant focal endometrial masses.
Is ultrasound elastography adding value in diagnosis of focal hepatic lesions? Our experience in a single-center study
Authors: Emara Doaa M. , El Shafei Mohamed M. , El-Gendi Ahmed , Yousif Amany A.
Published: December 2019

Background

The aim of this study was to assess the use of ultrasound elastography in differentiating hepatic lesions in order to increase the sensitivity and specificity of grey-scale ultrasound.

Methods

This study included 104 patients who were referred to the radiology department at Alexandria Main University Hospital for focal hepatic lesions detected by grey-scale ultrasound and were recommended to undergo further evaluation by ultrasound elastography. All studied patients were subjected to the following: (1) grey-scale ultrasound and ultrasound elastography using semiquantitative technique and (2) triphasic MDCT of the liver. MRI was done in 11 patients with malignant lesions; further confirmation with histopathological assessment was conducted.

Results

Benign lesions showed a low strain ratio, while malignant lesions showed a high strain ratio. The mean ratio in the benign lesions was 1.08 ± 0.40, while the mean ratio in the malignant lesions was 4.14 ± 1.25. The cut-off value used to diagnose the malignant lesions and differentiate these lesions from the benign lesions was 1.7, which had a sensitivity of 100%, specificity of 93.10%, PPV of 97.40% and NPV of 100%.

Conclusion

Ultrasound elastography is a promising non-invasive, non-contrast technique that can be added to routine grey-scale sonographic examinations of the liver to characterize hepatic lesions.
Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment
Authors: Morales-Palomo Felix , Ramirez-Jimenez Miguel , Ortega Juan F , Moreno-Cabañas Alfonso , Mora-Rodriguez Ricardo
Published: December 2019

Background

Statins reduce atherogenic dyslipidemia and cardiovascular disease (CVD) risk in metabolic syndrome (MetS) individuals. Exercise training could also contribute to reduce CVD by improving cardiorespiratory fitness and fat oxidation. However, statin use could interfere with training adaptations.

Methods

A total of 106 MetS individuals were divided into statin users (statin group, n = 46) and statin-naïve (control group, n = 60). Groups were matched by age, weight, and MetS components. Subjects completed 16 weeks of high intensity interval training (HIIT). Before and after HIIT, muscle biopsies were collected to assess mitochondrial content (citrate synthase [CS] activity) and the activity of the rate limiting β-oxidation enzyme (3-hydroxyacyl-CoA-dehydrogenase [HAD]). Fasting plasma glucose, insulin, TG, HDL-c, and LDL-c concentrations were measured. Exercise maximal fat oxidation (FOMAX) and oxygen uptake (VO2PEAK) were determined.

Results

Training improved MetS similarly in both groups (MetS z-score -0.26 ± 0.38 vs. -0.22 ± 0.31; P < 0.001 for time and P = 0.60 for time x group). Before training, the statin group had reduced muscle HAD activity and whole body FOMAX compared to the control group. However, 16 weeks of HIIT increased HAD and FOMAX in both groups (P < 0.03, time-effect). The statin group did not prevent the increases in CS with HIIT observed in the control group (38% vs 64%, respectively; P < 0.001, time-effect). Conversely, with training VO2PEAK improved less in the statin than in the control group (12% vs. 19%, respectively; P = 0.013, time × group effect).

Conclusion

Chronic statin use in MetS does not interfere with exercise training improvements in MetS components, FOMAX, or mitochondrial muscle enzymes (ie, CS and HAD). However, the statin group attenuated the improvements in VO2PEAK with training.

Clinical Trial Information

ClinicalTrials.gov identifier no. NCT03019796, January 13, 2017.
Ovarian Androgens Maintain High GnRH Neuron Firing Rate in Adult Prenatally-Androgenized Female Mice
Authors: Dulka Eden A , Burger Laura L , Moenter Suzanne M
Published: December 2019

Changes in gonadotropin-releasing hormone (GnRH) release frequency from the brain help drive reproductive cycles. In polycystic ovary syndrome (PCOS), persistent high GnRH/luteinizing hormone (LH) frequency disrupts cycles and exacerbates hyperandrogenemia. Adult prenatally-androgenized (PNA) mice exhibit increased GnRH neuron firing rate, elevated ovarian androgens, and disrupted cycles, but before puberty, GnRH neuron activity is reduced in PNA mice compared with controls. We hypothesized that ovarian feedback mediates the age-dependent change in GnRH neuron firing rate in PNA vs control mice. Extracellular recordings of green fluorescent protein (GFP)-identified GnRH neurons were made 5 to 7 days after sham-surgery, ovariectomy (OVX), or, in adults, after OVX plus replacement of sub-male androgen levels with dihydrotestosterone implants (OVX + DHT). In 3-week-old mice, OVX did not affect GnRH neuron firing rate in either group. In adult controls, OVX increased GnRH neuron firing rate, which was further enhanced by DHT. In adult PNA mice, however, OVX decreased GnRH neuron firing rate, and DHT restored firing rate to sham-operated levels. In contrast to the differential effects of ovarian feedback on GnRH neuron firing rate, serum LH increased after OVX in both control and PNA mice and was not altered by DHT. Pituitary gene expression largely reflected changes expected with OVX, although in PNA but not control mice, DHT treatment increased Lhb expression. These results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback. PNA lowers GnRH neuron activity in low-steroid states (before puberty, OVX), and renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens.
MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides
Authors: Agbu Pamela , Cassidy Justin J , Braverman Jonathan , Jacobson Alec , Carthew Richard W
Published: December 2019

The insulin/insulin-like growth factor (IGF) pathway is essential for linking nutritional status to growth and metabolism. MicroRNAs (miRNAs) are short RNAs that are players in the regulation of this process. The miRNA miR-7 shows highly conserved expression in insulin-producing cells across the animal kingdom. However, its conserved functions in regulation of insulin-like peptides (ILPs) remain unknown. Using Drosophila as a model, we demonstrate that miR-7 limits ILP availability by inhibiting its production and secretion. Increasing miR-7 alters body growth and metabolism in an ILP-dependent manner, elevating circulating sugars and total body triglycerides, while decreasing animal growth. These effects are not due to direct targeting of ILP mRNA, but instead arise through alternate targets that affect the function of ILP-producing cells. The Drosophila F-actin capping protein alpha (CPA) is a direct target of miR-7, and knockdown of CPA in insulin-producing cells phenocopies the effects of miR-7 on ILP secretion. This regulation of CPA is conserved in mammals, with the mouse ortholog Capza1 also targeted by miR-7 in β-islet cells. Taken together, these results support a role for miR-7 regulation of an actin capping protein in insulin regulation, and highlight a conserved mechanism of action for an evolutionarily ancient microRNA.
Effects of Long-Term Exercise on Liver Cyst in Polycystic Liver Disease Model Rats
Authors: SATO YOICHI , QIU JIAHE , MIURA TAKAHIRO , KOHZUKI MASAHIRO , ITO OSAMU
Published: December 2019

Background

Polycystic liver disease (PLD) is a hereditary liver disease with progressive enlargement of fluid-filled liver cysts, which causes abdominal discomfort and worsens quality of life. Long-term exercise has beneficial effects in various organs, but the effects of long-term exercise on PLD are unclear. Therefore, the aim of this study was to investigate whether long-term exercise inhibits liver cyst formation and fibrosis.

Methods

Polycystic kidney (PCK) rats, a model of PLD, were randomly divided into a sedentary group and a long-term exercise group, which underwent treadmill running for 12 wk (28 m·min−1, 60 min·d−1, 5 d·wk−1). Sprague–Dawley (SD) rats were set as a control group. After 12 wk, exercise capacity, histology, and signaling cascades of PLD were examined.

Results

Compared with control SD rats, PCK rats showed a low exercise capacity before exercise protocol. After 12 wk, the exercise improved the exercise capacity and ameliorated liver cyst formation and fibrosis. The exercise significantly decreased the number of Ki-67-positive cells; the expression of cystic fibrosis transmembrane conductance regulator, aquaporin 1, transforming growth factor β, and type 1 collagen; and the phosphorylation of extracellular signal–regulated kinase, mammalian target of rapamycin and S6. It also increased the phosphorylation of AMP-activated protein kinase in the liver of PCK rats.

Conclusions

The present results indicated that long-term moderate-intensity exercise ameliorates liver cyst formation and fibrosis with the inhibition of signaling cascades responsible for cellular proliferation and fibrosis in PCK rats.
Accumulation of Skeletal Muscle T Cells and the Repeated Bout Effect in Rats
Authors: DEYHLE MICHAEL R. , CARLISLE MEGHAN , SORENSEN JACOB R. , HAFEN PAUL S. , JESPERSON KYLIE , AHMADI MOHADESEH , HANCOCK CHAD R. , HYLDAHL ROBERT D.
Published: December 2019

Purpose

The purpose of this investigation was to characterize skeletal muscle T-cell accumulation after contraction-induced muscle damage and test the hypothesis that T cells contribute to postdamage muscle protection (i.e., the repeated bout effect) in a way reminiscent of their role in adaptive immunity.

Methods

In vivo lengthening contractions were used to model the repeated bout effect and contralateral repeated bout effect in rats. Intramuscular T-cell subsets were characterized by flow cytometry after single and repeated bouts of lengthening contractions, and an adoptive T-cell transfer experiment was done to test whether T cells from muscle damage-experienced rats can confer protection from injury to damage-naive rats.

Results

Electrically stimulated lengthening contractions elicited the repeated bout effect, but not the contralateral repeated bout effect. Although leukocytes (CD45+) were scarce in undamaged muscle (2.1% of all cells), substantially more (63% of all cells) were observed after a single bout of lengthening contractions. Within the leukocyte population were several subsets of T cells, including conventional CD4+, CD8+, memory, and regulatory T cells. In contrast, a minimal increase in T cells was observed after a second bout of lengthening contractions. Conventional CD4+ T cells (FoxP3−) were the most abundant subset in muscle after lengthening contractions. Adoptive T-cell transfer from damage-experienced rats did not confer protection to damage-naive recipient rats.

Conclusions

The robust T-cell accumulation, particularly the CD4 subset, after contraction-induced damage suggests a role for these cells in muscle repair and adaptation to muscle damaging contractions. Moreover, T cells are unlikely to mediate the protective adaptations of the repeated bout effect in a manner similar to their role in adaptive immunity.
Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries
Authors: MOGHADAM NAVID , HIEDA MICHINARI , RAMEY LINDSAY , LEVINE BENJAMIN D. , GUILLIOD RENIE
Published: December 2019

Hyperbaric oxygen therapy (HBOT) is a well-established treatment for a variety of conditions. Hyperbaric oxygen therapy is the administration of 100% oxygen breathing in a pressure vessel at higher than atmospheric pressure (1 atmosphere absolute = 101 kPa). Typically, treatment is given daily for between 1 and 2 h at pressures of 2.0 to 2.8 ATA, depending on the indication. Sporting injuries are often treated over 3 to 10 sessions. Hyperbaric oxygen therapy has been documented to be effective and is approved in 14 medical indications by the Undersea and Hyperbaric Medical Society, including, but not limited to, carbon monoxide poisoning, compromised skin grafts and flaps, crush injuries, necrotizing soft tissue infections, and nonhealing ulcers with arterial insufficiencies. Recently, HBOT for sports musculoskeletal injuries is receiving increased attention. Hyperbaric oxygen therapy may allow injured athletes to recover faster than normal rehabilitation methods. Any reduction in collegiate and professional athletes’ rehabilitation period can be financially significant for top-level sports teams; however, further research is required to confirm HBOT’s benefits on sports musculoskeletal injuries. The purpose of this review to discuss the current understanding of HBOT as a treatment modality for common musculoskeletal injuries in sport medicine. Moreover, we will highlight the advantages and disadvantages of this modality, as well as relevant clinical and research applications.
Heavy Resistance Training in Breast Cancer Patients Undergoing Adjuvant Therapy
Authors: CEŠEIKO RŪDOLFS , THOMSEN SIMON NØRSKOV , TOMSONE SIGNE , EGLĪTIS JĀNIS , VĒTRA AIVARS , SREBNIJS ANDREJS , TIMOFEJEVS MIHAILS , PURMALIS EGĪLS , WANG EIVIND
Published: December 2019

Background and Purpose

Adjuvant breast cancer therapy may reduce maximal muscle strength, muscle mass, and functional performance. Although maximal strength training (MST) has the potential to counteract this debilitating outcome and is shown to be superior to low- and moderate-intensity strength training, it is unknown if it can elicit effective adaptations in patients suffering treatment-induced adverse side effects.

Methods

Fifty-five newly diagnosed stage I to III breast cancer patients (49 ± 7 yr) scheduled for adjuvant therapy were randomized to MST or a control group. The MST group performed 4 × 4 repetitions of dynamic leg press at approximately 90% of one-repetition maximum (1RM) twice a week for 12 wk.

Results

In the MST group, improvements in 1RM (20% ± 8%; P < 0.001) were accompanied by improved walking economy (9% ± 8%) and increased time to exhaustion during incremental walking (9% ± 8%; both P < 0.01). Moreover, the MST group increased 6-min walking distance (6MWD; 10% ± 7%), and chair rising (30% ± 20%) and stair climbing performance (12% ± 7%; all P < 0.001). All MST-induced improvements were different from the control group (P < 0.01) which reduced their 1RM (9% ± 5%), walking economy (4% ± 4%), time to exhaustion (10% ± 8%), 6MWD (5% ± 5%), chair rising performance (12% ± 12%), and stair climbing performance (6% ± 8%; all P < 0.01). Finally, although MST maintained estimated quadriceps femoris muscle mass, a decrease was observed in the control group (7% ± 10%; P < 0.001). The change in 1RM correlated with the change in walking economy (r = 0.754), time to exhaustion (r = 0.793), 6MWD (r = 0.807), chair rising performance (r = 0.808), and stair climbing performance (r = 0.754; all P < 0.001).

Conclusions

Lower-extremity MST effectively increases lower-extremity maximal muscle strength in breast cancer patients undergoing adjuvant therapy and results in improved work economy, functional performance, and maintenance of muscle mass. These results advocate that MST should be considered in breast cancer treatment.
The landscape of eukaryotic mRNPs
Authors: Khong Anthony , Parker Roy
Published: December 2019

The proper regulation of mRNA processing, localization, translation, and degradation occurs on mRNPs. However, the global principles of mRNP organization are poorly understood. We utilize the limited, but existing, information available to present a speculative synthesis of mRNP organization with the following key points. First, mRNPs form a compacted structure due to the inherent folding of RNA. Second, the ribosome is the principal mechanism by which mRNA regions are partially decompacted. Third, mRNPs are 50%–80% protein by weight, consistent with proteins modulating mRNP organization, but also suggesting the majority of mRNA sequences are not directly interacting with RNA-binding proteins. Finally, the ratio of mRNA-binding proteins to mRNAs is higher in the nucleus to allow effective RNA processing and limit the potential for nuclear RNA based aggregation. This synthesis of mRNP understanding provides a model for mRNP biogenesis, structure, and regulation with multiple implications.
Evaluating the Risks and Benefits of Genetic and Pharmacologic Interventions for Down Syndrome: Views of Parents
Authors: Riggan Kirsten A. , Nyquist Christina , Michie Marsha , Allyse Megan A.
Published: December 2019

Researchers are investigating new technologies to mitigate or prevent symptoms of Down syndrome (DS), including chromosome silencing and pharmacotherapy. We surveyed parents of individuals with DS to assess their opinions on two hypothetical scenarios describing prenatal chromosome silencing and pediatric pharmacological intervention to improve neurocognition in children with DS. Although a slim majority of participants supported the availability of both therapies, respondent support was contingent on the risks presented, including the risk of miscarriage in the prenatal intervention and the impact of pharmaceuticals on their children's personality. Many parents expressed ambivalence, articulating a desire to improve their children's quality of life but requiring more safety and efficacy research before agreeing to a genetic or pharmacological intervention.
Adverse Medication Events Related to Hospitalization in the United States: A Comparison Between Adults With Intellectual and Developmental Disabilities and Those Without
Authors: Erickson Steven R. , Kamdar Neil , Wu Chung-Hsuen
Published: December 2019

This study examined the proportion of hospitalizations associated with adverse medication events (AMEs) for adults with intellectual and developmental disabilities (IDD) and adults from the general population in the United States using the 2013 National Inpatient Sample (NIS) dataset of the Healthcare Cost and Utilization Project (HCUP). Adults with IDD had greater odds of having a hospitalization associated with an AME than the general adult population. Unadjusted odds ratios (95% CI) for hospitalization due to any medication for IDD was 2.47 (2.31–2.65). In the multivariate logistic regression model, IDD was significantly associated, with an odds ratio of 1.28 (1.19–1.38). Adults who have IDD are at greater risk of having a hospital admission due to an AME.
Enhanced radiation resistance of ytterbium-doped silica fiber by pretreating on a fiber preform
Authors: Shao Chongyun , Jiao Yan , Lou Fengguang , Wang Meng , Zhang Lei , Feng Suya , Wang Shikai , Chen Danping , Yu Chunlei , Hu Lili
Published: December 2019

We propose a new pretreatment method on fiber preforms by loading deuterium (D2), pre-irradiation, combined with thermal annealing. The effect of the pretreatment condition on the optical loss at 1200 nm and a laser slope efficiency of ytterbium-doped silica fibers (YDFs) before and after γ-radiation was comparatively investigated. The related mechanism was revealed by combining the optical absorption, continuous wave electron paramagnetic resonance (CW-EPR), Raman, and Fourier transform infrared (FTIR) spectroscopies. A laser experiment shows that the radiation resistance of YDFs can be significantly improved by the pretreatment on a fiber preform. Also, this new pretreatment method has no obvious negative impact on the laser performance of non-irradiated YDFs. Furthermore, the vacuum experiment confirms that the YDF obtained by this method, named pretreated YDF, may have a long-term radiation stability when it is used in a vacuum environment (such as space). CW-EPR spectra show that the formation of color centers was effectively inhibited in pretreated YDF, which is correlated with the decrease of color center precursor and the existence of the deuterium radical as confirmed by Raman and FTIR spectra.