bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of MicroRNA-423-5p in posttranscriptional regulation of the intestinal riboflavin transporter-3
Authors: Lakhan Ram , Subramanian Veedamali S. , Said Hamid M.
Published: September 2017

Riboflavin (RF) is essential for normal cellular functions and health. Humans obtain RF from exogenous sources via intestinal absorption that involves a highly specific carrier-mediated process. We have recently established that the riboflavin transporter-3 (RFVT3) is vital for the normal intestinal RF uptake process and have characterized certain aspects of its transcriptional regulation. Little is known, however, about how this transporter is regulated at the posttranscriptional level. We address this issue by focusing on the role of microRNAs. Using bioinformatics, we identified two potential interacting miRNAs with the human (h) RFVT3-3′-UTR, and showed (using pmirGLO-hRFVT3-3′-UTR) that the hRFVT3-3′-UTR is, indeed, a target for miRNA effect. Of the two putative miRNAs identified, miR-423-5p was found to be highly expressed in intestinal epithelial cells and that its mimic affected luciferase reporter activity of the pmirGLO-hRFVT3-3′-UTR construct, and also led to inhibition in RF uptake by intestinal epithelial Caco-2 and HuTu-80 cells. Furthermore, cells transfected with mutated seed sequences for miR-423-5p showed an abrogation in inhibitory effect of the miR-423-5p mimic on luciferase activity. While miR-423-5p did not affect the level of expression of the hRFVT3 mRNA, it did lead to a significant inhibition in the level of expression of its protein. Similarly, miR-423-5p was found to affect the level of expression of the mouse RFVT3 in cultured intestinal enteroids. These findings demonstrate, for the first time, that the RFVT3 is a target for posttranscriptional regulation by miRNAs in intestinal epithelial cells and that this regulation has functional consequences on intestinal RF uptake.

NEW & NOTEWORTHY Our findings show for the first time that RFVT3 is a target for posttranscriptional regulation by miR-423-5p in intestinal epithelial cells, and this regulation has functional consequences on intestinal riboflavin (RF) uptake process.
Exposure of neonatal mice to bromine impairs their alveolar development and lung function
Authors: Jilling Tamas , Ren Changchun , Yee Aaron , Aggarwal Saurabh , Halloran Brian , Ambalavanan Namasivayam , Matalon Sadis
Published: September 2017

The halogen bromine (Br2) is used extensively in industry and stored and transported in large quantities. Its accidental or malicious release into the atmosphere has resulted in significant casualties. The pathophysiology of Br2-induced lung injury has been studied in adult animals, but the consequences of Br2 exposure to the developing lung are completely unknown. We exposed neonatal mouse littermates on postnatal day 3 (P3) to either Br2 at 400 ppm for 30 min (400/30), to Br2 at 600 ppm for 30 min (600/30), or to room air, then returned them to their dams and observed until P14. Mice exposed to Br2 had decreased survival (S) and had decreased weight (W) at P14 in the 400/30 group (S = 63.5%, W = 6.67 ± 0.08) and in the 600/30 group (S = 36.1%, W = 5.13 ± 0.67) as compared with air breathing mice (S = 100%, W = 7.96 ± 0.30). Alveolar development was impaired, as evidenced by increased mean linear intercept at P14. At P14, Br2 exposed mice also exhibited a decrease of arterial partial pressure of oxygen, decreased quasi-static lung compliance, as well as increased alpha smooth muscle actin mRNA and protein and increased mRNA for IL-1β, IL-6, CXCL1, and TNFα. Global gene expression, evaluated by RNA sequencing and Ingenuity Pathway Analysis, revealed persistent abnormalities in gene expression profiles at P14 involving pathways of “formation of lung” and “pulmonary development.” The data indicate that Br2 inhalation injury early in life results in severe lung developmental consequences, wherein persistent inflammation and global altered developmental gene expression are likely mechanistic contributors.
Complement C5a receptors C5L2 and C5aR in renal fibrosis
Authors: Martin Ina V. , Bohner Annika , Boor Peter , Shagdarsuren Erdenechimeg , Raffetseder Ute , Lammert Frank , Floege Jürgen , Ostendorf Tammo , Weber Susanne N.
Published: September 2017

Complement factor C5a has two known receptors, C5aR, which mediates proinflammatory effects, and C5L2, a potential C5a decoy receptor. We previously identified C5a/C5aR signaling as a potent profibrotic pathway in the kidney. Here we tested for the first time the role of C5L2 in renal fibrosis. In unilateral ureteral obstruction (UUO)-induced kidney fibrosis, the expression of C5aR and C5L2 increased similarly and gradually as fibrosis progressed and was particularly prominent in injured dilated tubules. Genetic deficiency of either C5aR or C5L2 significantly reduced UUO-induced tubular injury. Expression of key proinflammatory mediators, however, significantly increased in C5L2- compared with C5aR-deficient mice, but this had no effect on the number of renal infiltrating macrophages or T cells. Moreover, in C5L2−/−mice, the cytokine and matrix metalloproteinase-inhibitor tissue inhibitor of matrix metalloproteinase-1 was specifically enhanced. Consequently, in C5L2−/−mice the degree of renal fibrosis was similar to wild type (WT), albeit with reduced mRNA expression of some fibrosis-related genes. In contrast, C5aR−/−mice had significantly reduced renal fibrosis compared with WT and C5L2−/−mice in UUO. In vitro experiments with primary tubular cells demonstrated that deficiency for either C5aR or C5L2 led to a significantly reduced expression of tubular injury and fibrosis markers. Vice versa, stimulation of WT tubular cells with C5a significantly induced the expression of these markers, whereas the absence of either receptor abolished this induction. In conclusion, in experimental renal fibrosis C5L2 and C5aR both contribute to tubular injury, and, while C5aR acts profibrotic, C5L2 does not play a role in extracellular matrix accumulation, arguing against C5L2 functioning simply as a decoy receptor.
Influence of past injurious exercise on fiber type-specific acute anabolic response to resistance exercise in skeletal muscle
Authors: Takagi Ryo , Ogasawara Riki , Takegaki Junya , Tsutaki Arata , Nakazato Koichi , Ishii Naokata
Published: September 2017

We investigated the influence of past injurious exercise on anabolic response of skeletal muscle fibers to resistance exercise (RE). Wistar rats were divided into exercise (E) and exercise-after-injury (I-E) groups. At age 10 wk, the right gastrocnemius muscle in each rat in the I-E group was subjected to strenuous eccentric contractions. Subsequently, RE was imposed on the same muscle of each rat at 14 wk of age in both groups. Peak joint torque and total force generation per body mass during RE were similar between the groups. Muscle protein synthesis (MPS) in the I-E group was higher than that in the E group 6 h after RE. Furthermore, levels of phospho-p70S6 kinase (Thr389) and phospho-ribosomal protein S6 (phospho-rpS6) (Ser240/244), a downstream target of p70S6 kinase, were higher in the I-E group than in the E group. For the anabolic response in each fiber type, the I-E group showed a higher MPS response in type IIb, IIa, and I fibers and a higher phospho-rpS6 response in type IIx, IIa, and I fibers than the E group. In the I-E group, the relative content of myosin heavy chain (MHC) IIa was higher and that of MHC IIb was lower than those in the E group. In addition, type IIa fibers showed a lower MPS response to RE than type IIb fibers in the I-E group. In conclusion, the past injurious exercise enhanced the MPS and phospho-rpS6 responses in type IIb, IIa, and I fibers and type IIx, IIa, and I fibers, respectively.

NEW & NOTEWORTHY Past injurious exercise increased the muscle protein synthesis (MPS) response and mammalian target of rapamycin complex 1 (mTORC1) signaling activation to resistance exercise. In the responses of each fiber type, the past injurious exercise increased the MPS and phosphorylation ribosomal protein (Ser240/244) responses in type IIb, IIa, and I fibers and type IIx, IIa, and I fibers, respectively.
Immune Thrombocytopenia in a Child with Neuroblastoma
Authors: Ikizoglu Hasan Tarkan , Ayan Inci , Tokat Fatma , Tecimer Tulay , Topuzlu Tekant Gonca
Published: September 2017

Thrombocytopenia is a frequent finding in patients with solid tumors. It is usually caused by bone marrow infiltration or by myelosuppression due to anticancer therapy; however immune thrombocytopenia (ITP) associated with solid tumors is rare. Neuroblastoma is the most common extracranial solid tumor in children. Here we report the case of a two-year-nine-month-old patient with adrenal neuroblastoma who presented with ITP. Paraneoplastic ITP was considered in the differential diagnosis. Bone marrow infiltration and other causes of thrombocytopenia were excluded and the patient was treated with intravenous immunoglobulin and tumor resection. Platelet count increased rapidly after surgery and complete remission of ITP was achieved.
Accelerating the HyperLogLog Cardinality Estimation Algorithm
Authors: Bozkus Cem , Fraguela Basilio B.
Published: September 2017

In recent years, vast amounts of data of different kinds, from pictures and videos from our cameras to software logs from sensor networks and Internet routers operating day and night, are being generated. This has led to new big data problems, which require new algorithms to handle these large volumes of data and as a result are very computationally demanding because of the volumes to process. In this paper, we parallelize one of these new algorithms, namely, the HyperLogLog algorithm, which estimates the number of different items in a large data set with minimal memory usage, as it lowers the typical memory usage of this type of calculation from O(n) to O(1). We have implemented parallelizations based on OpenMP and OpenCL and evaluated them in a standard multicore system, an Intel Xeon Phi, and two GPUs from different vendors. The results obtained in our experiments, in which we reach a speedup of 88.6 with respect to an optimized sequential implementation, are very positive, particularly taking into account the need to run this kind of algorithm on large amounts of data.
Endothelinergic Contractile Hyperreactivity in Rat Contralateral Carotid to Balloon Injury: Integrated Role for ETB Receptors and Superoxide Anion
Authors: Pernomian Larissa , Gimenes Lilian R. , Gomes Mayara S. , do Vale Bruno N. , Cardoso Cristina R. B. , de Oliveira Ana M. , Moreira Josimar D.
Published: September 2017

Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in left carotid and were treated with CP-96345 (NK1 antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or presence of BQ-123 (ETA antagonist), BQ-788 (ETB antagonist), or Tempol (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol. Endothelin-1-induced NADPH oxidase-driven superoxide generation was measured by lucigenin chemiluminescence assays performed with BQ-123 or BQ-788. Endothelin-1-induced contraction was increased in contralateral carotid from the sixteenth day after surgery. This response was restored in CP-96345-treated rats. Endothelium removal or BQ-123 did not change endothelin-1-induced contraction in contralateral carotid. This response was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced calcium mobilization, which was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced lucigenin chemiluminescence, which was restored by BQ-788. We conclude that the NK1-mediated neurocompensatory response to balloon injury elicits a contractile hyperreactivity to endothelin-1 in rat contralateral carotid by enhancing the muscular ETB-mediated NADPH oxidase-driven generation of superoxide, which activates calcium channels.
Mesenchymal Stem Cells in Sepsis and Associated Organ Dysfunction: A Promising Future or Blind Alley?
Authors: Horák Jan , Nalos Lukáš , Martínková Vendula , Beneš Jan , Štengl Milan , Matějovič Martin
Published: September 2017

Sepsis, newly defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is the most common cause of death in ICUs and one of the principal causes of death worldwide. Although substantial progress has been made in the understanding of fundamental mechanisms of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. In this context, the immune-reprogramming properties of cell-based therapy using mesenchymal stem cells (MSC) represent an emerging therapeutic strategy in sepsis and associated organ dysfunction. This article provides an update of the current knowledge regarding MSC in preclinical models of sepsis and sepsis-induced acute kidney injury. Recommendations for further translational research in this field are discussed.
Alcohol Inhibits Odontogenic Differentiation of Human Dental Pulp Cells by Activating mTOR Signaling
Authors: Qin Wei , Huang Qi-Ting , Weir Michael D. , Song Zhi , Fouad Ashraf F. , Lin Zheng-Mei , Zhao Liang , Xu Hockin H. K.
Published: September 2017

Long-term heavy alcohol consumption could result in a range of health, social, and behavioral problems. People who abuse alcohol are at high risks of seriously having osteopenia, periodontal disease, and compromised oral health. However, the role of ethanol (EtOH) in the biological functions of human dental pulp cells (DPCs) is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs through the mechanistic target of rapamycin (mTOR) remains unexplored. The objective of this study was to investigate the effects of EtOH on DPC differentiation and mineralization. DPCs were isolated and purified from human dental pulps. The proliferation and odontoblastic differentiation of DPCs treated with EtOH were subsequently investigated. Different doses of EtOH were shown to be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase activity, attenuated the mineralized nodule formation, and suppressed the expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN. Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly reversed the EtOH-induced odontoblastic differentiation and cell mineralization. Our findings show for the first time that EtOH can suppress DPC differentiation and mineralization in a mTOR-dependent manner, indicating that EtOH may be involved in negatively regulating the dental pulp repair.
PD-1 Status in CD8+ T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer
Authors: Kansy Benjamin A. , Concha-Benavente Fernando , Srivastava Raghvendra M. , Jie Hyun-Bae , Shayan Gulidanna , Lei Yu , Moskovitz Jessica , Moy Jennifer , Li Jing , Brandau Sven , Lang Stephan , Schmitt Nicole C. , Freeman Gordon J. , Gooding William E. , Clump David A. , Ferris Robert L.
Published: September 2017

Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1+ TIL has been reported in human papillomavirus (HPV)+ HNC patients, despite the role of PD-1 in T-cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T-cell function and prognostic impact, because PD-1high T cells may be more exhausted than PD-1low T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy. In this study, PD-1 expression was indeed upregulated on HNC patient TIL, and the frequency of these PD-1+ TIL was higher in HPV+ patients (P = 0.006), who nonetheless experienced significantly better clinical outcome. However, PD-1high CD8+ TILs were more frequent in HPV− patients and represented a more dysfunctional subset with compromised IFN-γ secretion. Moreover, HNC patients with higher frequencies of PD-1high CD8+ TIL showed significantly worse disease-free survival and higher hazard ratio for recurrence (P < 0.001), while higher fractions of PD-1low T cells associated with HPV positivity and better outcome. In a murine HPV+ HNC model, anti-PD-1 mAb therapy differentially modulated PD-1high/low populations, and tumor rejection associated with loss of dysfunctional PD-1high CD8+ T cells and a significant increase in PD-1low TIL. Thus, the extent of PD-1 expression on CD8+ TIL provides a potential biomarker for anti-PD-1–based immunotherapy. Cancer Res; 77(22); 6353–64. ©2017 AACR.
Extracellular S100A9 Protein in Bone Marrow Supports Multiple Myeloma Survival by Stimulating Angiogenesis and Cytokine Secretion
Authors: De Veirman Kim , De Beule Nathan , Maes Ken , Menu Eline , De Bruyne Elke , De Raeve Hendrik , Fostier Karel , Moreaux Jérôme , Kassambara Alboukadel , Hose Dirk , Heusschen Roy , Eriksson Helena , Vanderkerken Karin , Van Valckenborgh Els
Published: September 2017

Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples. We showed that S100A9 acted as a chemoattractant for MM cells and induced MDSCs to express and secrete inflammatory and pro-myeloma cytokines, including TNFα, IL6, and IL10. Blocking S100A9 interactions in vivo with the small molecule ABR-238901 did not directly affect MDSC accumulation but did reduce IL6 and IL10 cytokine expression by MDSC. ABR-238901 treatment in vivo reduced angiogenesis but had only minor effects on tumor load as single agent (6% reduction). However, ABR-238901 treatment in combination with bortezomib resulted in an increased reduction in tumor load compared with single treatments (50% relative reduction compared with bortezomib alone). Our data suggest that extracellular S100A9 promotes MM and that inhibition of S100A9 may have therapeutic benefit. Cancer Immunol Res; 5(10); 839–46. ©2017 AACR.
Cerebral Fat Embolism: Clinical Presentation, Diagnostic Steps and Long-Term Follow-Up
Authors: Dunkel Juliane , Roth Christian , Erbguth Frank , Dietrich Wenke , Hügens-Penzel Monika , Ferbert Andreas
Published: September 2017

Objective: Symptomatic cerebral fat embolism (CFE) is a rare complication that occurs after a traumatic injury or orthopaedic surgery and is diagnostically challenging. No data is currently available concerning long-term follow-up. Methods: We identified from medical records 9 patients with CFE and revised the clinical signs and the diagnostic process. We then analysed long-term follow-up data, targeting clinical course after discharge, neurological impairment, and current quality of life, using the Barthel index and the modified Rankin Scale. Results: All 9 patients initially showed severe neurological deficits, including disturbance of consciousness ranging from somnolence to coma. During the follow-up period for 3–58 months after the insult 2 patients had died. The 7 patients who remained alive had either recovered completely or showed only minor neurological deficits after rehabilitation. They were nearly independent in daily life and needed only minimal assistance. We performed the first brain biopsy in a patient with CFE. Conclusion: Most patients had a good outcome after long-term follow-up. In patients with an unexplained altered state of consciousness after a traumatic injury or an orthopaedic surgery, an MRI with diffusion-weighted imaging must be performed to uncover the characteristic pattern of disseminated hyperintense lesions in the white matter that are associated with CFE.
Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma
Authors: Oki Eiji , Okano Shinji , Saeki Hiroshi , Umemoto Yuichiro , Teraishi Koji , Nakaji Yu , Ando Koji , Zaitsu Yoko , Yamashita Nami , Sugiyama Masahiko , Nakashima Yuichiro , Ohgaki Kippei , Oda Yoshinao , Maehara Yoshihiko
Published: September 2017

Objectives: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. Materials and Methods: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. Results: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. Conclusions: PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1.
The Outcome and Patterns of Traumatic Brain Injury in the Paediatric Population of a Developing Country Secondary to TV Trolley Tip-Over
Authors: Waqas Muhammad , Javed Gohar , Nathani Karim Rizwan , Ujjan Badar , Quadri Syed A. , Tahir Muhammad Zubair
Published: September 2017

Background: Television (TV) trolley tip-over incidences are common and can cause significant morbidity and mortality in children. This study was aimed at analyzing the pattern and outcomes of head injuries resulting from TV trolley tip-over. Method: We conducted a medical chart review of children with TV trolley tip-over head injuries from January 2009 to April 2016. We collected data on demographics, the mechanism of injury, clinical and radiological features of the injury, and outcomes. Outcomes were measured by means of the Glasgow Outcome Scale (GOS) at 6 months (except in 1 case). A descriptive analysis was carried out using SPSS v19. Result: Twenty-two children were included in the study (median age 23.5 months). Sixteen children were male. Most of the children (n = 16) were aged 12-35 months. The median Glasgow Coma Scale score on admission was 15. The median Rotterdam Score for the patients was 2.0. Common symptoms upon admission were vomiting, irritability, scalp laceration, and bruises. Median length of hospital stay was 3 days. Skull bone fractures were present in 12 children. Other CT findings included contusions, extradural and subdural haematomas, intraventricular haemorrhage, and pneumocranium. Surgical intervention was required in 4 cases. Although most of the patients made a good recovery (GOS = 5), 1 patient developed a mild disability and another died in hospital. Conclusion: TV trolley tip-over is most common in toddlers and can lead to significant head injury and mortality. This can be avoided by parental supervision and adjustments in the household.
Posterior Hemi-/Laminectomy and Facetectomy Approach for the Treatment of Dumbbell-Shaped Schwannomas in the Subaxial Cervical Spine: A Retrospective Study of 26 Cases
Authors: Huang Yong , Wang Zuowei , Chen Zan , Wu Hao , Jian Fengzeng
Published: September 2017

Objective: It is difficult to completely and safely remove a tumor that is located in the subaxial cervical spine by using the posterior approach because of the anatomical characteristics. Previous reports regarding the total removal of subaxial schwannomas using the one-stage posterior approach are still limited. This study was to evaluate the feasibility and efficacy of treating the dumbbell-shaped schwannomas in the subaxial cervical spine using the one-stage posterior approach. Methods: Patients with dumbbell-shaped schwannomas in the subaxial cervical spine were treated using the one-stage posterior approach. Surgical profile, clinical outcomes, MRI and X-ray images, and complications were investigated. Japanese Orthopaedic Association (JOA) score and McCormick functional schema score were obtained. Results: The average follow-up was 21.5 ± 5.1 months, with a range of 12–31 months. Twenty-six patients were enrolled in the study. Total resection was achieved in all patients using the one-stage posterior approach with hemi- or laminectomy and facetectomy. All cases underwent lateral mass screw fixation and fusion. JOA improved significantly (p < 0.01). The McCormick score improved significantly (p < 0.05) after the surgery. No mortality, morbidity, or tumor recurrence was observed during the follow-up period. Conclusion: Our technique was feasible and effective for the treatment of dumbbell schwannomas in the subaxial cervical spine. The tumor could be totally removed in most cases safely.
Feasibility and Effectiveness of Intervention Programmes Integrating Functional Exercise into Daily Life of Older Adults: A Systematic Review
Authors: Weber Michaela , Belala Nacera , Clemson Lindy , Boulton Elisabeth , Hawley-Hague Helen , Becker Clemens , Schwenk Michael
Published: September 2017

Background: Traditionally, exercise programmes for improving functional performance and reducing falls are organised as structured sessions. An alternative approach of integrating functional exercises into everyday tasks has emerged in recent years. Objectives: Summarising the current evidence for the feasibility and effectiveness of interventions integrating functional exercise into daily life. Methods: A systematic literature search was conducted including articles based on the following criteria: (1) individuals ≥60 years; (2) intervention studies of randomised controlled trials (RCTs) and non-randomised studies (NRS); (3) using a lifestyle-integrated approach; (4) using functional exercises to improve strength, balance, or physical functioning; and (5) reporting outcomes on feasibility and/or effectiveness. Methodological quality of RCTs was evaluated using the PEDro scale. Results: Of 4,415 articles identified from 6 databases, 14 (6 RCTs) met the inclusion criteria. RCT quality was moderate to good. Intervention concepts included (1) the Lifestyle-integrated Functional Exercise (LiFE) programme integrating exercises into everyday activities and (2) combined programmes using integrated and structured training. Three RCTs evaluated LiFE in community dwellers and reported significantly improved balance, strength, and functional performance compared with controls receiving either no intervention, or low-intensity exercise, or structured exercise. Two of these RCTs reported a significant reduction in fall rate compared with controls receiving either no intervention or low-intensity exercise. Three RCTs compared combined programmes with usual care in institutionalised settings and reported improvements for some (balance, functional performance), but not all (strength, falls) outcomes. NRS showed behavioural change related to LiFE and feasibility in more impaired populations. One NRS comparing a combined home-based programme to a gym-based programme reported greater sustainability of effects in the combined programme. Conclusions: This review provides evidence for the effectiveness of integrated training for improving motor performances in older adults. Single studies suggest advantages of integrated compared with structured training. Combined programmes are positively evaluated in institutionalised settings, while little evidence exists in other populations. In summary, the approach of integrating functional exercise into daily life represents a promising alternative or complement to structured exercise programmes. However, more RCTs are needed to evaluate this concept in different target populations and the potential for inducing behavioural change.
Pancreatic Adenocarcinoma Masquerading as Idiopathic Chronic Pancreatitis with Delayed Diagnosis
Authors: Badami Sunil , Kyi Htay Htay , Upadhaya Sunil , Al Hadidi Samer
Published: September 2017

Pancreatic cancer carries poor prognosis. Establishing the diagnosis early could help in improving outcome. We are presenting a case of pancreatic cancer with delayed diagnosis. Our 60-year-old patient underwent multiple endoscopic ultrasound-guided biopsies with no evidence of malignancy. He had normal molecular tumor biomarkers. The patient needed 8 months to receive the diagnosis and initiate the treatment. There are no specific guidelines regarding choice of tissue sampling modalities in such cases.
Mechanisms of Targeting the MDM2-p53-FOXM1 Axis in Well-Differentiated Intestinal Neuroendocrine Tumors
Authors: Briest Franziska , Grass Irina , Sedding Dagmar , Möbs Markus , Christen Friederike , Benecke Joana , Fuchs Karolin , Mende Stefanie , Kaemmerer Daniel , Sänger Jörg , Kunze Almut , Geisler Christina , Freitag Helma , Lewens Florentine , Worpenberg Lina , Iwaszkiewicz Sara , Siegmund Britta , Walther Wolfgang , Hummel Michael , Grabowski Patricia
Published: September 2017

Background/Aims: The tumor suppressor p53 is rarely mutated in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) but they frequently show a strong expression of negative regulators of p53, rendering these tumors excellent targets for a p53 recovery therapy. Therefore, we analyzed the mechanisms of a p53 recovery therapy on intestinal neuroendocrine tumors in vitro and in vivo.Methods: By Western blot and immunohistochemistry, we found that in GEP-NEN biopsy material overexpression of MDM2 was present in intestinal NEN. Therefore, we analyzed the effect of a small-molecule inhibitor, nutlin-3a, in p53 wild-type and mutant GEP-NEN cell lines by proliferation assay, flow cytometry, immunofluorescence, Western blot, and by multiplex gene expression analysis. Finally, we analyzed the antitumor effect of nutlin-3a in a xenograft mouse model in vivo. During the study, the tumor volume was determined. Results: The midgut wild-type cell line KRJ-I responded to the treatment with cell cycle arrest and apoptosis. By gene expression analysis, we could demonstrate that nutlins reactivated an antiproliferative p53 response. KRJ-I-derived xenograft tumors showed a significantly decreased tumor growth upon treatment with nutlin-3a in vivo. Furthermore, our data suggest that MDM2 also influences the expression of the oncogene FOXM1 in a p53-independent manner. Subsequently, a combined treatment of nutlin-3a and cisplatin (as chemoresistance model) resulted in synergistically enhanced antiproliferative effects. Conclusion: In summary, MDM2 overexpression is a frequent event in p53 wild-type intestinal neuroendocrine neoplasms and therefore recovery of a p53 response might be a novel personalized treatment approach in these tumors.
Nueva especie de rana bromelícola del género Pristimantis (Amphibia: Craugastoridae), meseta de la Cordillera del Cóndor, Ecuador
Authors: Brito M. Jorge , Almendáriz C. Ana , Batallas R. Diego , Ron Santiago R.
Published: September 2017

We describe a small frog of the genus Pristimantis inhabiting bromeliads (snout-vent length 20.3‑23.3 mm in females, 16.1‑17.4 mm in males), from a remote sandstone plateau of the Cordillera del Condor, in southeastern Ecuador, with an altitudinal range of 2,045‑2,860 m. A phylogeny based on sequences of DNA (mitochondrial and nuclear genes) supports inclusion in the P. orestes group and suggests an undescribed Pristimantis from the southern slope of eastern Ecuador as the closest taxon. The new species differs from its congeners in Ecuador by having predominantly black dorsal and ventral coloration; comprehensive and robust palmar surface with stubby fingers; presence of a deep and wide groove from the anterior base of finger I to the rear base of the palmar tubercle; subarticular divided tubers, enlarged supernumerary small granules and tubercles. All individuals were found in terrestrial bromeliads. The calls are short, frequency modulated, comprising of a note 5‑15 ms in duration. Insects represented 80% of the diet of the new species.
New range limit of the Anopetia gounellei (Aves: Trochilidae): state of art and a review on the updated area
Authors: Nolasco Erica Csekö , Franca-Rocha Washington de Jesus Sant'anna da , Moura Thiago , Pinto-Ledezma Jesús N.
Published: September 2017

New technologies and the rapid amount of data help to improve and update the distribution of the species. Anopetia gounellei (Broad-tipped Hermit, Trochilidae) is a poorly known hummingbird and has been recorded outside its formal range since 2009. Here we reviewed the records of the Broad-tipped Hermit, proposing new range limits and discussing the species ecoregional endemism. The species was recorded in a variety of vegetation, including caatinga and humid forest. Our updated range-limit suggest an increase of 80% from the previous range, exceeding the Caatinga limits, calling into question the endemism of the species to this biome, but confirming a close relationship with dry ecoregions in Brazil. Basic information about its biology is needed, and further studies about breeding and ecological requirements are recommended.
Dilated Cardiomyopathy
Authors: McNally Elizabeth M. , Mestroni Luisa
Published: September 2017

Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.
Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease
Authors: Wanner Christoph , Lachin John M. , Inzucchi Silvio E. , Fitchett David , Mattheus Michaela , George Jyothis , Woerle Hans J. , Broedl Uli C. , von Eynatten Maximilian , Zinman Bernard
Published: September 2017

Background:

Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease in the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.

Methods:

Patients with type 2 diabetes mellitus, established cardiovascular disease, and estimated glomerular filtration rate (eGFR) ≥30 mL·min
−1
·1.73 m
−2
at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. We analyzed cardiovascular death, hospitalization for heart failure, all-cause hospitalization, and all-cause mortality in patients with prevalent kidney disease (defined as eGFR <60 mL·min
−1
·1.73 m
−2
and/or urine albumin-creatinine ratio >300 mg/g) at baseline. Additional analyses were performed in subgroups by baseline eGFR (<45, 45–<60, 60–<90, ≥90 mL·min
−1
·1.73 m
−2
) and baseline urine albumin-creatinine ratio (>300, 30–≤300, <30 mg/g).

Results:

Of 7020 patients treated, 2250 patients had prevalent kidney disease at baseline, of whom 67% had a diagnosis of type 2 diabetes mellitus for >10 years, 58% were receiving insulin, and 84% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In patients with prevalent kidney disease at baseline, empagliflozin reduced the risk of cardiovascular death by 29% compared with placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52–0.98), the risk of all-cause mortality by 24% (HR, 0.76; 95% CI, 0.59–0.99), the risk of hospitalization for heart failure by 39% (HR, 0.61; 95% CI, 0.42–0.87), and the risk of all-cause hospitalization by 19% (HR, 0.81; 95% CI, 0.72–0.92). Effects of empagliflozin on these outcomes were consistent across categories of eGFR and urine albumin-creatinine ratio at baseline and across the 2 doses studied. The adverse event profile of empagliflozin in patients with eGFR <60 mL·min
−1
·1.73 m
−2
was consistent with the overall trial population.

Conclusions:

Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01131676.
Five new species of Parapercis (Perciformes: Pinguipedidae) from southeast Asia and northwest Australia
Authors: JOHNSON JEFFREY W. , MOTOMURA HIROYUKI
Published: September 2017

Five new species of sandperch (Pinguipedidae: Parapercis) from southeast Asia and northwest Australia are described. Parapercis soliorta sp. nov., known from a single specimen acquired from the Iloilo Central Market, taken off Iloilo, Panay Island, Philippines, is readily distinguished by a unique colour pattern including a series of nine brilliant yellow-ringed red spots along the body and caudal fin. Parapercis rubricaudalis sp. nov. is described from 15 specimens trawled between Dampier and Cape Leveque, Western Australia in 70–119 m and a single specimen taken by aquarium fish collectors off Zambales, Luzon, Philippines. It has the posterior end of the opercular ridge armed with two or three strong spines, the margin of the preopercle, subopercle and interopercle strongly serrated, and colouration including six broad irregular orange to reddish bands across the body, and the pelvic fins and lower third of the caudal fin crimson-red. A complex of three closely related species, Parapercis flavipinna sp. nov. from the Philippines, Parapercis caudopellucida sp. nov. from Myanmar and Parapercis hoi sp. nov. from northwest Australia and the Philippines, share a series of six or seven irregular dusky double blotches along the sides, a series of small black spots along the base of the soft dorsal-fin, a pair of dusky blotches on the caudal-fin base, and mostly similar meristic values. Parapercis hoi sp. nov. is known from four specimens trawled off Broome, Western Australia, in 97–109 m and one specimen trawled in the Sibuyan Sea, Philippines, in 73–84 m. It may be distinguished from its two closest congeners by cycloid cheek scales, a distinctive anal-fin colouration, and lower pectoral-fin ray, gill raker and lateral-line scale counts. Parapercis caudopellucida sp. nov., trawled in 125–129 m in the Andaman Sea off southern Myanmar, is described from two specimens. It differs from its two closest congeners most obviously by cycloid cheek scales, caudal-fin colouration, and the presence of a dusky bar extending posteroventrally from the tip of the maxilla to the anteroventral edge of the preopercle. Parapercis flavipinna sp. nov. is described from two specimens acquired from the Iloilo Central Market, taken off Iloilo, Panay Island, in the Philippines. It is distinguished most readily by the presence of ctenoid cheek scales and colouration including rows of bright yellow spots on the anal and caudal fins, a yellow upper lip, a series of yellow streaks and spots on the head, and fleshy pectoral-fin base with a large dark purplish grey blotch followed by a distinct white-edged black bar.
Interdisciplinary Management of Pediatric Obesity: Lessons Learned in the Midsouth
Authors: Burton E. Thomaseo , Smith Webb A. , Thurston Idia B. , Gray Emily , Perry Virginia , Jogal Sachin , Han Joan C.
Published: September 2017

The Healthy Lifestyle Clinic (HLC) is an interdisciplinary weight management clinic conceived to address alarming rates of pediatric obesity and related comorbidities in the midsouth region of the United States. The clinical cohort presented is a subset of the 609 patients evaluated during the first 2 years of the HLC and comprises 380 patients with a minimum of 6 months of follow-up. The primarily non-Hispanic black (67.1%) cohort presented with severe obesity ( MzBMI = 2.52 ± 0.41) and particularly high rates of insulin resistance, among other comorbidities. This article offers insight into the challenges of intervening with a cohort of youth and their families, many with limited resources to support intensive behavioral and lifestyle changes. Our experiences implementing a weight management clinic with a diverse clinical cohort provide guidance for emerging programs and impetus to investigate environmental and cultural factors that contribute to high attrition in the treatment of pediatric obesity.
Raising cervical cancer awareness: Analysing the incremental efficacy of Short Message Service
Authors: Lemos Marina Serra , Rothes Inês Areal , Oliveira Filipa , Soares Luisa
Published: September 2017

Objective:

To evaluate the incremental efficacy of a Short Message Service (SMS) combined with a brief video intervention in increasing the effects of a health education intervention for cervical cancer prevention, over and beyond a video-alone intervention, with respect to key determinants of health behaviour change – knowledge, motivation and intention.

Methodology:

Quasi-experimental study design, comparing three conditions – control group, video intervention group and SMS + video intervention group. Participants were 144 Portuguese female college students allocated into one of the three experimental conditions. The effects of the health education interventions were assessed using a theoretically based multidimensional cancer prevention questionnaire. Data were collected at baseline and post-test.

Results:

Interventions significantly increased the key predictors of adhesion to cancer preventive behaviours. SMS contributed to increases in the expected directions. Evidence of the superiority in efficacy of the combined intervention (SMS + video) over the video-alone intervention was found for cervical cancer screening. Interventions were not as effective in improving intentions and more complex preventive practices such as sexual behaviour as they were in improving knowledge.

Conclusion:

Results are encouraging in that cervical cancer prevention knowledge and motivation appear modifiable via a one-session video preventive intervention. If, however, the development of intentions is an important predictor of effective behaviour change, study findings point to the added importance of an SMS-based strategy for improving specific cancer preventive behaviours. Findings reinforce the need for specific and tailored health education interventions according to the various determinants of behaviour change, as well as to the particular target behaviour with respect to cervical cancer prevention.
Grounding Teacher Education in Practice Around the World: An Examination of Teacher Education Coursework in Teacher Education Programs in Finland, Norway, and the United States
Authors: Jenset Inga Staal , Klette Kirsti , Hammerness Karen
Published: September 2017

Worldwide, teacher educators and policy makers have called for teacher preparation that is more deeply linked to practice. Yet we know little about how such linkages are achieved within different international programs. We examine the degree to which programs provide opportunities to learn that are grounded in practice, during university coursework. We report on observation data ( N = 104 hr) from the methods courses in six programs in Finland, Norway, and California. Using an analytical framework decomposing the conception of “grounding in practice” in teacher education, this article provides evidence regarding the successes and challenges of incorporating practice in teacher education.
A Contextual Behavior Science Framework for Understanding How Behavioral Flexibility Relates to Anxiety
Authors: Palm Reed Kathleen M. , Cameron Amy Y. , Ameral Victoria E.
Published: September 2017

There is a growing literature focusing on the emerging idea that behavioral flexibility, rather than particular emotion regulation strategies per se, provides greater promise in predicting and influencing anxiety-related psychopathology. Yet this line of research and theoretical analysis appear to be plagued by its own challenges. For example, middle-level constructs, such as behavioral flexibility, are difficult to define, difficult to measure, and difficult to interpret in relation to clinical interventions. A key point that some researchers have made is that previous studies examining flexible use of emotion regulation strategies (or, more broadly, coping) have failed due to a lack of focus on context. That is, examining strategies in isolation of the context in which they are used provides limited information on the suitability, rigid adherence, or effectiveness of a given strategy in that situation. Several of these researchers have proposed the development of new models to define and measure various types of behavioral flexibility. We would like to suggest that an explanation of the phenomenon already exists and that we can go back to our behavioral roots to understand this phenomenon rather than focusing on defining and capturing a new process. Indeed, thorough contextual behavioral analyses already yield a useful account of what has been observed. We will articulate a model explaining behavioral flexibility using a functional, contextual framework, with anxiety-related disorders as an example.