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https://www.readbyqxmd.com/read/28644392/development-of-bone-targeting-drugs
#1
REVIEW
Molly Stapleton, Kazuki Sawamoto, Carlos J Alméciga-Díaz, William G Mackenzie, Robert W Mason, Tadao Orii, Shunji Tomatsu
The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca(2+)...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28643719/alkaptonuria-a-case-report
#2
Nirupama Damarla, Prathima Linga, Mallika Goyal, Sanjay Reddy Tadisina, G Satyanarayana Reddy, Hymavathi Bommisetti
Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of homogentisic acid in connective tissues (ochronosis). Most common ocular manifestations are bluish-black discoloration of the conjunctiva, cornea, and sclera. In this case report, a 39-year-old Indian male patient with additional ocular features in the retina is described.
June 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28643188/impact-of-appropriateness-of-empiric-therapy-on-outcomes-in-community-onset-bacteremia-by-extended-spectrum-%C3%AE-lactamase-producing-escherichia-coli-and-klebisella-pneumoniae-definitively-treated-with-carbapenems
#3
E-J Joo, D A Park, N R Lee, S-Y Moon, J-K Choi, J-H Ko, K R Peck
Despite a significant increase of bloodstream infection caused by extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems...
June 23, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28642694/ehlers-danlos-syndrome-hypermobility-type-impact-of-somatosensory-orthoses-on-postural-control-a-pilot-study
#4
Emma G Dupuy, Pascale Leconte, Elodie Vlamynck, Audrey Sultan, Christophe Chesneau, Pierre Denise, Stéphane Besnard, Boris Bienvenu, Leslie M Decker
Elhers-Danlos syndrome (EDS) is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS) is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28642621/variants-of-the-abca3-gene-might-contribute-to-susceptibility-to-interstitial-lung-diseases-in-the-chinese-population
#5
Wei Zhou, Yi Zhuang, Jiapeng Sun, Xiaofen Wang, Qingya Zhao, Lizhi Xu, Yaping Wang
ATP-binding cassette A3 (ABCA3) is a phospholipid carrier that is mainly expressed in the alveolar epithelium. Biallelic mutations of ABCA3 has been associated with fatal respiratory distress syndrome and interstitial lung disease (ILD) in children. However, whether variations in ABCA3 have a role in the development of adult ILD, including idiopathic pulmonary fibrosis (IPF), remains to be addressed. In this study, we screened for germline variants of ABCA3 by exons-sequencing in 30 patients with sporadic IPF and in 30 matched healthy controls...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642586/lateral-habenula-regulation-of-emotional-hyperthermia-mediation-via-the-medullary-raph%C3%A3
#6
Youichirou Ootsuka, Mazher Mohammed, William W Blessing
The lateral habenula (LHb) has an important role in the behavioural response to salient, usually aversive, events. We previously demonstrated that activation of neurons in the LHb increases brown adipose tissue (BAT) thermogenesis and constricts the cutaneous vascular bed, indicating that the LHb contributes to the central control of sympathetic outflow to thermoregulatory effector organs. We have now investigated whether the LHb mediates BAT thermogenesis elicited by emotional stress, and whether the LHb modulates thermoregulatory sympathetic outflow via the rostral medullary raphé, a key integrative lower brainstem sympathetic control centre...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641551/nailfold-capillaroscopy-within-and-beyond-the-scope-of-connective-tissue-diseases
#7
Sevdalina Lambova, Ulf Müller-Ladner
Nailfold capillaroscopy is a noninvasive instrumental method for morphological analysis of the nutritive capillaries in the nailfold area. In rheumatology, it is a method of choice among instrumental modalities for differentiation of primary and secondary Raynaud's phenomenon (RP) in rheumatic diseases. RP is a common diagnostic problem in rheumatology. Defining the proper diagnosis is a prerequisite for administration of the appropriate treatment. Thus, nailfold capillaroscopic examination is of crucial importance for the every-day practice of the rheumatologists and is currently gaining increasing attention...
June 14, 2017: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/28639945/pulmonary-arterial-hemodynamic-assessment-by-a-novel-index-in-systemic-lupus-erythematosus-patients-pulmonary-pulse-transit-time
#8
Tolga Han Efe, Mehmet Doğan, Cem Özişler, Tolga Çimen, Mehmet Ali Felekoğlu, Ahmet Göktuğ Ertem, Engin Algül, Sadık Açıkel
OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic, inflammatory, and autoimmune connective tissue disease. One of the leading causes of mortality among SLE patients is pulmonary hypertension. The aim of this study was to evaluate the association between echocardiographic findings, including the pulmonary pulse transit time and pulmonary hypertension parameters, in SLE patients. METHODS: Thirty SLE patients (aged 39.9±11 years, 28 females) as the study group and 34 age- and sex-matched healthy volunteers (aged 37...
June 22, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28639748/expansion-of-the-phenotype-of-kosaki-overgrowth-syndrome
#9
Mari Minatogawa, Toshiki Takenouchi, Yu Tsuyusaki, Fuminori Iwasaki, Tomoko Uenara, Kenji Kurosawa, Kenjiro Kosaki, Cynthia J Curry
Skeletal overgrowth is a characteristic of several genetic disorders that are linked to specific molecular signaling cascades. Recently, we established a novel overgrowth syndrome (Kosaki overgrowth syndrome, OMIM #616592) arising from a de novo mutation in PDGFRB, that is, c.1751C>G p.(Pro584Arg). Subsequently, other investigators provided in vitro molecular evidence that this specific mutation in the juxtamembrane domain of PDGFRB causes an overgrowth phenotype and is the first gain-of-function point mutation of PDGFRB to be reported in humans...
June 22, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28639403/writing-with-fluid-structuring-hydrogels-with-micrometer-precision-by-afm-in-combination-with-nanofluidics
#10
Nicolas Helfricht, Andreas Mark, Marina Behr, Andreas Bernet, Hans-Werner Schmidt, Georg Papastavrou
Hydrogels have many applications in biomedical surface modification and tissue engineering. However, the structuring of hydrogels after their formation represents still a major challenge, in particular due to their softness. Here, a novel approach is presented that is based on the combination of atomic force microscopy (AFM) and nanofluidics, also referred to as FluidFM technology. Its applicability is demonstrated for supramolecular hydrogel films that are prepared from low-molecular weight hydrogelators, such as derivates of 1,3,5-benzene tricarboxamides (BTAs)...
June 22, 2017: Small
https://www.readbyqxmd.com/read/28638428/acute-respiratory-failure-as-the-first-manifestation-of-antisynthetase-syndrome
#11
Sonia Toujani, Amani Ben Mansour, Meriem Mjid, Abir Hedhli, Jouda Cherif, Yassine Ouahchy, Majed Beji
We report the case of a 40-year-old man with acute respiratory failure syndrome that later proved to be an initial manifestation of antisynthetase syndrome. The diagnosis of this rare combination of a connective tissue disease and an acute respiratory failure is difficult in a previously asymptomatic patient. Early diagnosis and immunosuppressive therapy started precociously prevented the disease progression and resulted in a good outcome.
2017: Tanaffos
https://www.readbyqxmd.com/read/28638345/heterogeneity-and-developmental-connections-between-cell-types-inhabiting-teeth
#12
REVIEW
Jan Krivanek, Igor Adameyko, Kaj Fried
Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix-producing populations: ameloblasts generating enamel and odontoblasts producing dentin...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28638011/-collagen-types-ratio-in-prediction-of-postoperative-ventral-hernias
#13
V A Lazarenko, S V Ivanov, I S Ivanov, E P Rosberg, A V Tsukanov, L P Popova, D V Tarabrin, E G Obyedkov
AIM: To analyze collagen types ratio in skin and aponeurosis in order to predict postoperative ventral hernias. MATERIAL AND METHODS: The trial included 141 patients for the period 2012-2015. Group I (n=65) of patients without ventral hernias was divided into subgroup AI (primary operation, n=41) and BI (re-operation, n=24). Group II consisted of 76 patients with ventral hernias. We performed histological examination of skin and aponeurosis to define the collagen structure of connective tissue...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28636876/tissue-alignment-enhances-remodeling-potential-of-tendon-derived-cells-lessons-from-a-novel-microtissue-model-of-tendon-scarring
#14
Jasper Foolen, Stefania L Wunderli, Sandra Loerakker, Jess G Snedeker
Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue...
June 18, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28636382/development-of-efficient-chemistry-to-generate-site-specific-disulfide-linked-protein-and-peptide-payload-conjugates-application-to-thiomab%C3%A2-antibody-drug-conjugates
#15
Jack David Sadowsky, Thomas H Pillow, Jinhua Chen, Fang Fan, Changrong He, Yanli Wang, Gang Yan, Hui Yao, Zijin Xu, Shanique Martin, Donglu Zhang, Phillip Chu, Josefa Dela Cruz-Chuh, Aimee O'Donohue, Guangmin Li, Geoffrey Del Rosario, Jintang He, Luna Liu, Carl K Ng, Dian Su, Gail D Lewis Phillips, Katherine Ruth Kozak, Shang-Fan Yu, Keyang Xu, Douglas Leipold, John S Wai
Conjugation of small molecule payloads to specific cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28635230/-the-expression-of-programmed-death-receptor-1-in-non-small-cell-lung-cancer-and-its-clinicopathological-features-and-prognosis-showed-a-connection-with-epidermal-growth-factor-receptor-gene-mutations
#16
H Yin, C G Liao, Y Q Wang, Z Li, L L Fan, M L Qian, N Lu
Objective: To investigate the relationships between the expression of programmed death 1 (PD-1) and the epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). The study also attempted to investigate the clinicopathological features and prognosis in NSCLC patients. Methods: The expression of PD-1 protein in 88 cases of NSCLC tumor tissues and adjacent tissues was detected by immunohistochemistry. The mutations of EGFR in NSCLC were detected by Polymerase Chain Reaction-Amplification Refractory Mutation System(PCR-ARMS) method...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28634845/histomorphometric-and-immunohistochemical-evaluation-of-collagen-containing-xenogeneic-bone-blocks-used-for-lateral-bone-augmentation-in-staged-implant-placement
#17
Alberto Ortiz-Vigón, Sergio Martinez-Villa, Iñaki Suarez, Fabio Vignoletti, Mariano Sanz
BACKGROUND: The osteoconductive properties of collagen containing xenogeneic bone blocks (CCXBB) remain unclear. The aim of this prospective single-arm clinical study was to assess the histological outcomes of CCXBB blocks used as bone replacement grafts for lateral bone augmentation procedures. METHODS: In 15 patients with severe horizontal alveolar ridge resorption, lateral augmentation procedures were performed using CCXBB as bone replacement grafts. Twenty-six weeks postoperatively, a re-entry procedure was performed to evaluate the bone width for adequate implant placement and two histological specimens were retrieved from each patient, one being processed for ground sectioning and the other for decalcified paraffin-included sections...
December 2017: International Journal of Implant Dentistry
https://www.readbyqxmd.com/read/28634841/patient-related-risk-factors-for-postoperative-infection-after-cholecystectomy
#18
Gona Jaafar, Folke Hammarqvist, Lars Enochsson, Gabriel Sandblom
BACKGROUND: The impact of patient-related risk factors on the incidence of postoperative infection after cholecystectomy is relatively unknown. AIM: The aim of this study was to explore potential patient-related risk factors for surgical site infection (SSI) and septicaemia following cholecystectomy. MATERIALS AND METHODS: All cholecystectomies registered in the Swedish national population-based register for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) 2006-2014 were identified...
June 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28634201/phosphoproteomic-profiling-reveals-alk-and-met-as-novel-actionable-targets-across-synovial-sarcoma-subtypes
#19
Emmy D G Fleuren, Myrella Vlenterie, Winette van der Graaf, Melissa H S Hillebrandt-Roeffen, James Blackburn, Xiuquan Ma, Howard Chan, Mandy C Magias, Anke van Erp, Laurens van Houdt, Sabri Cebeci, Amy van de Ven, Uta E Flucke, Erin E Heyer, David M Thomas, Christopher J Lord, Kieren D Marini, Vijesh Vaghjiani, Tim Mercer, Jason E Cain, Jianmin Wu, Yvonne M H Versleijen-Jonkers, Roger J Daly
Despite intensive multi-modal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases...
June 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28634079/relaxin-reduces-susceptibility-to-post-infarct-atrial-fibrillation-in-mice-due-to-anti-fibrotic-and-anti-inflammatory-properties
#20
Thomas Beiert, Vedat Tiyerili, Vincent Knappe, Verena Effelsberg, Markus Linhart, Florian Stöckigt, Sabine Klein, Robert Schierwagen, Jonel Trebicka, Georg Nickenig, Jan W Schrickel, René P Andrié
BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps...
June 17, 2017: Biochemical and Biophysical Research Communications
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