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First-in-human clinical studies

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https://www.readbyqxmd.com/read/28441620/cognitive-behavioral-therapy-is-effective-in-misophonia-an-open-trial
#1
Arjan E Schröder, Nienke C Vulink, Arnoud J van Loon, Damiaan A Denys
BACKGROUND: Misophonia is a psychiatric disorder in which ordinary human sounds like smacking or chewing provoke intense anger and disgust. Despite the high burden of this condition, to date there is no evidence-based treatment available. In this study we evaluated the efficacy of cognitive behavioral therapy (CBT) and investigated whether clinical or demographic characteristics predicted treatment response. METHODS: Ninety patients with misophonia received eight bi-weekly group CBT sessions...
April 18, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28439730/physiological-and-therapeutic-regulation-of-pcsk9-activity-in-cardiovascular-disease
#2
REVIEW
Simon Glerup, Rainer Schulz, Ulrich Laufs, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and is accelerated by increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in the understanding of PCSK9 biology have been reported illustrating how PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28439230/from-anxious-to-reckless-a-control-systems-approach-unifies-prefrontal-limbic-regulation-across-the-spectrum-of-threat-detection
#3
REVIEW
Lilianne R Mujica-Parodi, Jiook Cha, Jonathan Gao
Here we provide an integrative review of basic control circuits, and introduce techniques by which their regulation can be quantitatively measured using human neuroimaging. We illustrate the utility of the control systems approach using four human neuroimaging threat detection studies (N = 226), to which we applied circuit-wide analyses in order to identify the key mechanism underlying individual variation. In so doing, we build upon the canonical prefrontal-limbic control system to integrate circuit-wide influence from the inferior frontal gyrus (IFG)...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28438110/temporal-progression-of-lesions-in-guinea-pigs-infected-with-lassa-virus
#4
T M Bell, C I Shaia, J J Bearss, M E Mattix, K A Koistinen, S P Honnold, X Zeng, C D Blancett, G C Donnelly, J D Shamblin, E R Wilkinson, K A Cashman
Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28437231/capsular-polysaccharide-types-and-virulence-related-traits-of-epidemic-kpc-producing-klebsiella-pneumoniae-isolates-in-a-chinese-university-hospital
#5
Yang Liu, Pan-Pan Liu, Lian-Hui Wang, Dan-Dan Wei, La-Gen Wan, Wei Zhang
Klebsiella pneumoniae is an important human pathogen associated with a variety of diseases and the prevalence of blaKPC carrying K. pneumoniae (KPC-Kp) is rapidly increasing. Capsule is an important virulence factor in K. pneumoniae. In this study, we determined to first systematically characterize capsular polysaccharide (CPS) and virulence traits in KPC-Kp strains. A total of 56 KPC-Kp isolates were recovered from clinical samples in a Chinese hospital, which were assigned to clonal lineages by multilocus sequence typing (MLST)...
February 24, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28436273/proteome-analysis-of-sheep-b-lymphocytes-in-the-course-of-bovine-leukemia-virus-induced-leukemia
#6
Michal Reichert
Presented are the results of a study of the expression pattern of different proteins in the course of bovine leukemia virus-induced leukemia in experimental sheep and I discuss how the obtained data may be useful in gaining a better understanding of the pathogenesis of the disease, diagnosis, and for the selection of possible therapeutic targets. In cattle, the disease is characterized by life-long persistent lymphocytosis leading to leukemia/lymphoma in about 5% of infected animals. In sheep, as opposed to cattle, the course of the disease is always fatal and clinical symptoms usually occur within a three-year period after infection...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28435012/il-10-down-regulates-the-expression-of-survival-associated-gene-hspx-of-mycobacterium-tuberculosis-in-murine-macrophage
#7
Babban Jee, Pawan Sharma, Kiran Katoch, Beenu Joshi, Sudhir Kumar Awasthi
Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50ng/ml) significantly down-regulated the hspX expression...
April 20, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28433777/design-and-expeditious-synthesis-of-organosilanes-as-potent-antivirals-targeting-multidrug-resistant-influenza-a-viruses
#8
Yanmei Hu, Yuanxiang Wang, Fang Li, Chunlong Ma, Jun Wang
The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433558/spatial-relationship-of-organized-rotational-and-focal-sources-in-human-atrial-fibrillation-to-autonomic-ganglionated-plexi
#9
Tina Baykaner, Theodoros A Zografos, Junaid A B Zaman, Ioannis Pantos, Mahmood Alhusseini, Rachita Navara, David E Krummen, Sanjiv M Narayan, Demosthenes G Katritsis
BACKGROUND: One approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP). METHODS: We prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59...
April 19, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28433372/intrinsic-fertility-of-human-oocytes
#10
Sherman J Silber, Keiichi Kato, Naoki Aoyama, Akiko Yabuuchi, Helen Skaletsky, Yuting Fan, Kazunori Shinohara, Noriyuki Yatabe, Tamotsu Kobayashi
OBJECTIVE: To study the intrinsic fertility of the human oocyte. DESIGN: A large retrospective study of natural cycle single embryo transfer (ET) IVF cycles. SETTING: Private IVF clinic, university, and private hospital. PATIENT(S): Patients were enrolled consecutively over an 8-year period in a single ET natural cycle protocol. INTERVENTION(S): A total of 13,949 oocyte retrievals with natural IVF single ET...
April 19, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28431931/peroxiredoxin-5-promotes-the-epithelial-mesenchymal-transition-in-colon-cancer
#11
Hye-Mi Ahn, Jin-Woo Yoo, Seunghoon Lee, Hong Jun Lee, Hyun-Shik Lee, Dong-Seok Lee
Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#12
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#13
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28430919/non-coding-rnas-in-cardiovascular-diseases-diagnostic-and-therapeutic-perspectives
#14
Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28429654/microrna-451-regulates-chemoresistance-in-renal-cell-carcinoma-by-targeting-atf-2-gene
#15
Xiang Sun, Longhua Lou, Kezhao Zhong, Lijuan Wan
Renal cell carcinoma (RCC) is a malignant tumor, which severely threatens human's life, moreover, the multi-drug resistance (MDR) under RCC undoubtedly strengthen the difficulties in the treatment. MiR-451 has been considered to play an important role in regulation of MDR in several cancers, but the role of it in MDR of RCC has not been explored. This study aims to explore the mechanism of miR-451 as a target to regulate chemotherapy resistance, which is crucial for further exploring novel therapy for RCC. Two human cell lines (ACHN and GRC-1) were performed in this study and adriamycin (ADM) was used to construct MDR cell lines...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428786/challenge-of-humans-with-wild-type-salmonella-enterica-serovar-typhi-elicits-changes-in-the-activation-and-homing-characteristics-of-mucosal-associated-invariant-t-cells
#16
Rosângela Salerno-Goncalves, David Luo, Stephanie Fresnay, Laurence Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8(+) MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28428733/microrna-338-3p-suppresses-cell-proliferation-and-induces-apoptosis-of-non-small-cell-lung-cancer-by-targeting-sphingosine-kinase-2
#17
Guowei Zhang, Hao Zheng, Guojun Zhang, Ruirui Cheng, Chunya Lu, Yijie Guo, Guoqiang Zhao
BACKGROUND: Lung cancer is the major cause of cancer-related death worldwide, and 80% patients of lung cancer are non-small-cell lung cancer (NSCLC) cases. MicroRNAs are important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Studies indicate that sphingosine kinase 2 (SphK2) promotes tumor progression in NSCLC, but how this occurs is unclear. Thus, we explored the effect of miR-338-3p targeting SphK2 on proliferation and apoptosis of NSCLC cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28427432/anti-human-platelet-antigen-hpa-1a-antibodies-may-affect-trophoblast-functions-crucial-for-placental-development-a-laboratory-study-using-an-in-vitro-model
#18
Mariana Eksteen, Gøril Heide, Heidi Tiller, Yan Zhou, Nora Hersoug Nedberg, Inigo Martinez-Zubiaurre, Anne Husebekk, Bjørn R Skogen, Tor B Stuge, Mette Kjær
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies...
April 21, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28427401/ki-67-protein-expression-and-tumor-associated-inflammatory-cells-macrophages-and-mast-cells-in-canine-colorectal-carcinoma
#19
M Woldemeskel, I Hawkins, L Whittington
BACKGROUND: Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC were compared with those in adenomas (n = 13) and control (n = 9). RESULTS: Ki-67 index in CRC (17...
April 20, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28427372/protocol-for-evaluation-of-the-continuum-of-primary-care-in-the-case-of-a-miscarriage-in-the-emergency-room-a-mixed-method-study
#20
Francine de Montigny, Chantal Verdon, Diane Dubeau, Annie Devault, Martin St-André, Éric Tchouaket Nguemeleu, Carl Lacharité
BACKGROUND: In Quebec (Canada), nearly 20,000 pregnancies end in miscarriage, and the majority of the miscarriages are dealt with in an emergency unit. Although there are studies documenting the effects of this type of grief on mental health, men's experiences are much less discussed than those of women. Similarly, no study has evaluated best practices in terms of service continuity, from emergency care to community resources. The aim of this study is to better understand the relationships that exist between the organization of emergency room and primary care health services for women presenting with miscarriage, on the one hand, and the positions and experiences of women and men within these services, on the other...
April 20, 2017: BMC Pregnancy and Childbirth
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