Hedges: This Week in Low-Tech Solutions for Climate Change

Bushes and shrubs may provide more targeted relief from air pollution

-- Read more on ScientificAmerican.com

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Fibrodysplasia ossificans progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP): A rare but dramatic genetic disorder that turns muscles, tendons and ligaments into bone, threatening to transform the victim into "a statue of stone."

FOP is characterized by physical handicap due to bone forming in the wrong places and malformed big toes which often contain only one bone. Other features of FOP can include short thumbs, fifth finger clinodactyly (pinkie curved toward the thumb), malformed cervical (neck) vertebrae, short broad neck of the femur (thighbone), deafness, scalp baldness, and mild mental retardation.

The average age at the onset of misplaced bone formation is 5 years (range: from birth to 25 years). The most common starting sites are the neck, spine, and shoulder girdle. Some restriction of movement is present in most (80%) cases by age 7 years. By the age of 15 years, more than 95% of the patients have severely restricted mobility of the arms.

Although progressive, FOP is not cancerous.

Inheritance of FOP is genetically a dominant trait. However, sporadic (with no known family history) cases occur and are due to new mutations.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Oral Cancer Awareness Walk & Run to take place Sept. 23 - New Jersey Herald

New Jersey Herald

Oral Cancer Awareness Walk & Run to take place Sept. 23 New Jersey Herald Approximately 49,750 Americans will be newly diagnosed with oral cancer this year, which includes mouth cancer, tongue cancer and throat cancer. When found early, there is an 80 to 90 percent survival rate. However, due to a lack of public awareness ...

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Viagra low cost - Viagra popytka nomer 5 mp3 - The Mainstream Online

Viagra low cost - Viagra popytka nomer 5 mp3 The Mainstream Online Buy real viagra online shout after 2 ED procedure madre srodku the years alcohol oni a who could Us Dysfunction pain Erectile a other What your had or the cancer President such. a interested they Family w the. .... Generic viagra approved by fda ... and more »

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Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Weilin Liu, Peiyuan Zhuo, Long Li, Hao Jin, Bingbing Lin, Yingzheng Zhang, Shengxiang Liang, Jie Wu, Jia Huang, Zhifu Wang, Ruhui Lin, Lidian Chen, Jing Tao
An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal ¹⁸F-Fluoro-2-deoxy-D-Glucose (¹⁸F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aβ) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aβ deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aβ deposition in a transgenic mouse model of AD.

Graphical abstract

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Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Seong-Eun Hong, Jiae Lee, Dong-Hyun Seo, Hye In Lee, Doo Ri Park, Gong-Rak Lee, You-Jin Jo, Narae Kim, Minjung Kwon, Hansem Shon, Eun Kyoung Seo, Han-Sung Kim, Soo Young Lee, Woojin Jeong
Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages. EFL1 inhibited receptor activator of NF-κB ligand (RANKL)-induced NFATc1 induction with attenuated NF-κB activation and c-Fos expression. EFL1 decreased the level of reactive oxygen species by scavenging them or activating Nrf2, and inhibited PGC-1β that regulates mitochondria biogenesis. In addition, EFL1 induced apoptosis in differentiated osteoclasts by increasing Fas ligand expression followed by caspase activation. Moreover, EFL1 inhibited inflammation-induced bone erosion and ovariectomy-induced bone loss in mice. These findings suggest that EFL1 inhibits osteoclast differentiation by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast, and may provide therapeutic potential for preventing or treating bone-related diseases caused by excessive osteoclast.

Graphical abstract

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Importance of NADPH oxidase-mediated redox signaling in the detrimental effect of CRP on pancreatic insulin secretion

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Pei-Chi Chan, Ya-Chin Wang, Yi-Ling Chen, Wan-Ning Hsu, Yu-Feng Tian, Po-Shiuan Hsieh
Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-β cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause β cell damage in state of inflammation.

Graphical abstract

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Epigenetic regulation of EC-SOD expression in aging lung fibroblasts: Role of histone acetylation

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jesse Roman, Jianxin Zhu, Jeffrey D. Ritzenthaler, Igor N. Zelko
Lung disorders characterized by fibroproliferation and excessive deposition of extracellular matrices occur in late adulthood, and their pathological manifestations become more prominent with aging. The exact mechanisms linking aging and fibroproliferative disorders are unknown, but increased oxidative stress resulting in the accumulation of damaged proteins, DNA, and lipids is considered a major factor. In the lung, and especially in the pulmonary fibroblasts, the extracellular superoxide dismutase (EC-SOD) is a major antioxidant enzyme that has been implicated in pulmonary fibrosing disorders, among others. Here, we investigate the regulation of EC-SOD in pulmonary lung fibroblasts derived from young (up to 3 month) and old (24 month) C57BL6 mice. We found that old fibroblasts have marginally elevated levels of reactive oxidant species (ROS), which coincides with attenuated expression a number of antioxidant enzymes including EC-SOD. Exposure of old fibroblasts to the DNA methyltransferase inhibitor 5-aza-dC did not restore expression of EC-SOD. On the other hand, repression of EC-SOD expression was associated with deacetylation of lysine 9 on histone H3 and lysines 5, 8, 12 and 16 on histone H4 located at the gene promoter. Interestingly, the repressive tri-methylation of lysine 27 on histone H3 was elevated in old compared to young fibroblasts. In addition, exposure of old lung fibroblasts to HDAC class 1 and class 2 inhibitors restored EC-SOD expression to the level observed in young fibroblasts. While the exact mechanism of age-dependent downregulation of EC-SOD is yet to be defined, our studies indicate a potential role of epigenetic mechanisms including histone deacetylation in this process.

Graphical abstract

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Intermittent hypoxia-induced cardiomyopathy and its prevention by Nrf2 and metallothionein

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Shanshan Zhou, Xia Yin, Jingpeng Jin, Yi Tan, Daniel J. Conklin, Ying Xin, Zhiguo Zhang, Weixia Sun, Taixing Cui, Jun Cai, Yang Zheng, Lu Cai
The mechanism for intermittent hypoxia (IH)-induced cardiomyopathy remains obscure. We reported the prevention of acute and chronic IH-induced cardiac damage by selective cardiac overexpression of metallothionein (MT). Herein we defined that MT-mediated protection from IH-cardiomyopathy is via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a critical redox-balance controller in the body. For this, mice were exposed to IH for 3 days (acute) or 4 or 8 weeks (chronic). Cardiac Nrf2 and MT expression in response to IH were significantly increased acutely yet decreased chronically. Interestingly, cardiac overexpression (Nrf2-TG) or global deletion of the Nrf2 gene (Nrf2-KO) made mice highly resistant or highly susceptible, respectively, to IH-induced cardiomyopathy and MT expression. Mechanistically, 4-week IH exposure significantly decreased cardiac Nrf2 binding to the MT gene promoter, and thus, depressed both MT transcription and translation in WT mice but not Nrf2-TG mice. Likewise, cardiac MT overexpression prevented chronic IH-induced cardiomyopathy and down-regulation of Nrf2 likely via activation of a PI3K/Akt/GSK-3β/Fyn-dependent signaling pathway. These results reveal an integrated relationship between cardiac Nrf2 and MT expression in response to IH -- acute compensatory up-regulation followed by chronic down-regulation and cardiomyopathy. Cardiac overexpression of either Nrf2 or MT offered cardioprotection from IH via complicated PI3K/Akt/GSK3B/Fyn signaling. Potential therapeutics may target either Nrf2 or MT to prevent chronic IH-induced cardiomyopathy.

Graphical abstract

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Peroxyl radical- and photo-oxidation of glucose 6-phosphate dehydrogenase generates cross-links and functional changes via oxidation of tyrosine and tryptophan residues

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Fabian Leinisch, Michele Mariotti, Martin Rykaer, Camilo Lopez-Alarcon, Per Hägglund, Michael J. Davies
Protein oxidation is a frequent event as a result of the high abundance of proteins in biological samples and the multiple processes that generate oxidants. The reactions that occur are complex and poorly understood, but can generate major structural and functional changes on proteins. Current data indicate that pathophysiological processes and multiple human diseases are associated with the accumulation of damaged proteins. In this study we investigated the mechanisms and consequences of exposure of the key metabolic enzyme glucose-6-phosphate dehydrogenase (G6PDH) to peroxyl radicals (ROO^•) and singlet oxygen (¹O2), with particular emphasis on the role of Trp and Tyr residues in protein cross-linking and fragmentation. Cross-links and high molecular mass aggregates were detected by SDS-PAGE and Western blotting using specific antibodies. Amino acid analysis has provided evidence for Trp and Tyr consumption and formation of oxygenated products (diols, peroxides, N-formylkynurenine, kynurenine) from Trp, and di-tyrosine (from Tyr). Mass spectrometric data obtained after trypsin-digestion in the presence of H2¹⁶O and H2¹⁸O, has allowed the mapping of specific cross-linked residues and their locations. These data indicate that specific Tyr-Trp and di-Tyr cross-links are formed from residues that are proximal and surface-accessible, and that the extent of Trp oxidation varies markedly between sites. Limited modification at other residues is also detected. These data indicate that Trp and Tyr residues are readily modified by ROO^• and ¹O2 with this giving products that impact significantly on protein structure and function. The formation of such cross-links may help rationalize the accumulation of damaged proteins in vivo.

Graphical abstract

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Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jan Blecha, Silvia Magalhaes Novais, Katerina Rohlenova, Eliska Novotna, Sandra Lettlova, Sabine Schmitt, Hans Zischka, Jiri Neuzil, Jakub Rohlena
Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 – thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g. in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death.

Graphical abstract

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Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac mitochondrial biogenesis in Diabetes

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Silvina S. Bombicino, Darío E. Iglesias, Ivana A. Rukavina-Mikusic, Bruno Buchholz, Ricardo J. Gelpi, Alberto Boveris, Laura B. Valdez
This study, in an experimental model of type I Diabetes Mellitus in rats, deals with the mitochondrial production rates and steady-state concentrations of H2O2 and NO, and ATP levels as part of a network of signaling molecules involved in heart mitochondrial biogenesis. Sustained hyperglycemia leads to a cardiac compromise against a work overload, in the absence of changes in resting cardiac performance and of heart hypertrophy. Diabetes was induced in male Wistar rats by a single dose of Streptozotocin (STZ, 60mg × kg^-1, ip.). After 28 days of STZ-injection, rats were sacrificed and hearts were isolated. The mitochondrial mass (mg mitochondrial protein × g heart^-1), determined through cytochrome oxidase activity ratio, was 47% higher in heart from diabetic than from control animals. Stereological analysis of cardiac tissue microphotographs showed an increase in the cytosolic volume occupied by mitochondria (30%) and in the number of mitochondria per unit area (52%), and a decrease in the mean area of each mitochondrion (23%) in diabetic respect to control rats. Additionally, an enhancement (76%) in PGC-1α expression was observed in cardiac tissue of diabetic animals. Moreover, heart mitochondrial H2O2 (127%) and NO (23%) productions and mtNOS expression (132%) were higher, while mitochondrial ATP production rate was lower (~ 40%), concomitantly with a partial-mitochondrial depolarization, in diabetic than in control rats. Changes in mitochondrial H2O2 and NO steady-state concentrations and an imbalance between cellular energy demand and mitochondrial energy transduction could be involved in the signaling pathways that lead to the novo synthesis of mitochondria. However, this compensatory mechanism triggered to restore the mitochondrial and tissue normal activities, did not lead to competent mitochondria capable of supplying the energetic demands in diabetic pathological conditions.

Graphical abstract

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The theory of autoimmunity in Meniere’s disease is lacking evidence

Publication date: Available online 4 August 2017
Source:Auris Nasus Larynx
Author(s): Eerik Kangasniemi, Elina Hietikko
The role of immunological factors in the pathophysiology of Meniere's disease (MD) has been hypothesized. In order to evaluate the current level of evidence on autoimmunity in MD, original articles relevant to the matter (1970–2016) were reviewed. The following has been considered to support the theory of autoimmunity in MD (1) the increased prevalence of autoimmune diseases among MD patients, (2) the elevated levels of antibodies and immunocomplexes in MD patients, (3) the association of MD with HLA-types and genetic polymorphisms and (4) the positive corticosteroid-responsiveness detected in some MD patients. However, all studies have been small and lack positive replication. Studies concerning antibodies, HLA types and genetic polymorphisms have produced conflicting results and no single antibody, HLA type or polymorphism has been found in all or even in a significant subpopulation of MD patients. No convincing basic research evidence of autoimmunity in MD exists hence the field needs further study.



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Cancer survivors urge need for regular checkups - Pontiac Daily Leader

Pontiac Daily Leader

Cancer survivors urge need for regular checkups Pontiac Daily Leader This year's honored survivors, Kathy Gragson of Cornell and David Haab of Hudson, spoke openly and honestly spoke about their battles with cancer, followed by a sincere speech of appreciation from this year's honored caregiver, Cathie Haab. ... "I kind ...

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Mapping QTL for Root and Shoot Morphological Traits in a Durum Wheat × T. dicoccum Segregating Population at Seedling Stage

A segregating population of 136 recombinant inbred lines derived from a cross between the durum wheat cv. "Simeto" and the T. dicoccum accession "Molise Colli" was grown in soil and evaluated for a number of shoot and root morphological traits. A total of 17 quantitative trait loci (QTL) were identified for shoot dry weight, number of culms, and plant height and for root dry weight, volume, length, surface area, and number of forks and tips, on chromosomes 1B, 2A, 3A, 4B, 5B, 6A, 6B, and 7B. LODs were 2.1 to 21.6, with percent of explained phenotypic variability between 0.07 and 52. Three QTL were mapped to chromosome 4B, one of which corresponds to the Rht-B1 locus and has a large impact on both shoot and root traits (LOD 21.6). Other QTL that have specific effects on root morphological traits were also identified. Moreover, meta-QTL analysis was performed to compare the QTL identified in the "Simeto" × "Molise Colli" segregating population with those described in previous studies in wheat, with three novel QTL defined. Due to the complexity of phenotyping for root traits, further studies will be helpful to validate these regions as targets for breeding programs for optimization of root function for field performance.

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Arterial Thoracic Outlet Syndrome Treated Successfully with Totally Endoscopic First Rib Resection

Thoracic outlet syndrome (TOS) is a constellation of signs and symptoms caused by compression of the neurovascular structures in the thoracic outlet. TOS may be classified as either neurogenic TOS (NTOS) or vascular TOS: venous TOS (VTOS) or arterial TOS (ATOS), depending on the specific structure being affected. The basis for the surgical treatment of TOS is resection of the first rib, and it may be combined with scalenectomy or cervical rib resection. Herein, we describe a case of arterial thoracic outlet syndrome which was successfully treated with totally endoscopic video-assisted thoracoscopic surgery (VATS) first rib resection.

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Overweight or Obesity, Gender, and Age Influence on High School Students of the City of Toluca’s Physical Fitness

Material and Method. This is a prospective, cross-sectional, and correlational study with a probabilistic sampling in which 150 teenagers from three different high schools from the city of Toluca, Mexico, aged 15–17, were assessed. Objective. To determine if weight, age, and gender have an influence on physical fitness evaluated with the EUROFIT and ALPHA-FITNESS batteries. Results. Women have a higher overweight and obesity rate than men (3 : 1). Adolescents who have normal weight have regular physical fitness (74.9%). When comparing genders we found that men have a higher mean than women in the tests, except for skinfold thickness and waist circumference. Age was only correlated with the plate tapping test . There are significant differences in the standing broad jump test and the Course-Navette of the EUROFIT and ALPHA-FITNESS batteries . Conclusions. It is likely that regular physical activity, and not normal weight, helps generate healthy physical fitness. Male subjects had a higher mean than women, reporting a better physical fitness and more frequent physical activity.

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Mapping QTL for Root and Shoot Morphological Traits in a Durum Wheat × T. dicoccum Segregating Population at Seedling Stage

A segregating population of 136 recombinant inbred lines derived from a cross between the durum wheat cv. "Simeto" and the T. dicoccum accession "Molise Colli" was grown in soil and evaluated for a number of shoot and root morphological traits. A total of 17 quantitative trait loci (QTL) were identified for shoot dry weight, number of culms, and plant height and for root dry weight, volume, length, surface area, and number of forks and tips, on chromosomes 1B, 2A, 3A, 4B, 5B, 6A, 6B, and 7B. LODs were 2.1 to 21.6, with percent of explained phenotypic variability between 0.07 and 52. Three QTL were mapped to chromosome 4B, one of which corresponds to the Rht-B1 locus and has a large impact on both shoot and root traits (LOD 21.6). Other QTL that have specific effects on root morphological traits were also identified. Moreover, meta-QTL analysis was performed to compare the QTL identified in the "Simeto" × "Molise Colli" segregating population with those described in previous studies in wheat, with three novel QTL defined. Due to the complexity of phenotyping for root traits, further studies will be helpful to validate these regions as targets for breeding programs for optimization of root function for field performance.

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Histologic and Histomorphometric Comparison between Sintered Nanohydroxyapatite and Anorganic Bovine Xenograft in Maxillary Sinus Grafting: A Split-Mouth Randomized Controlled Clinical Trial

The presence of vital bone after maxillary sinus augmentation is crucial to enhance the quality of bone-implant interface, ensuring predictable long-term results. The aims of this RCT with split-mouth design were the histologic and histomorphometric comparison of two different biomaterials in sinus elevation after 6 months of healing and the evaluation of the clinical outcomes of implants inserted in the augmented areas after 12 months of prosthetic loading. Twenty-eight patients (10 females, 18 males) were treated with bilateral sinus floor elevation with lateral approach. Pure sintered nanohydroxyapatite (NHA) and anorganic bovine bone (ABB) were used as test and active control, respectively. After six months, 52 bone biopsies were harvested from 26 patients, and 107 implants were inserted in the augmented areas. Histomorphometry showed that, in the two groups, vital bone percentages were % (NHA) and % (ABB) (), marrow spaces percentages were % (NHA) and % (ABB) (), and residual graft percentages were % (NHA) and % (ABB) (). After 6 months of healing, no statistically significant difference was present in histomorphometric outcomes between NHA and ABB groups. Implant survival rate in NHA group after 12 months of loading was 96.4%, showing no statistically significant differences with ABB group.

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Measurement of Pozzolanic Activity Index of Scoria, Pumice, and Rice Husk Ash as Potential Supplementary Cementitious Materials for Portland Cement

This work investigated the properties of scoria and pumice as supplementary cementitious materials (SCMs) for Portland cement and compared to those of rice husk ash (RHA). X-ray fluorescence, X-ray diffraction, and pozzolanic activity index (PAI) tests confirmed the suitability of these two materials as potential SCMs. Scoria and RHA samples achieved over 75% PAI at 7 days whereas pumice did this after 28 days. Initial and final mean setting times observed for the composite cement blended with these materials were 166 and 285 min, respectively. These setting times are longer than that of ordinary Portland cement but shorter compared to that of common Portland pozzolana cement. The ultimate mean compressive strengths achieved at 28 days of curing were 42.5, 44.8, and 43.0 MPa for scoria, pumice, and RHA, respectively, signifying that these materials are good SCMs. Higher fineness yielded higher ultimate mean strength. For instance, a scoria sample with a fineness of 575 m2/kg achieved the strength of 52.2 MPa after 28 days.

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Optimization of Roller Velocity for Quenching Machine Based on Heat Transfer Mathematical Model

During quenching process of steel plate, control parameters are important to product quality. In this work, heat transfer mathematical model has been developed for roller-type quenching machine to predict the temperature field of plate at first, and then an optimization schedule considering quenching technology and equipment limitations is developed firstly based on the heat transfer mathematical model with considering the shortest quenching time. A numerical simulation is performed during optimization process to investigate the effects of roller velocity on the temperature of representative plate. Based on the optimization method, study is also performed for different thickness of plate to obtain the corresponding roller velocity. The results show that the optimized roller velocity can be achieved for the roller-type continuous quenching machine based on the heat transfer mathematical model. With the increasing of plate's thickness, the optimized roller velocity decreases exponentially.

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Neuropsychological Outcome following Resuscitation after Out-of-Hospital Cardiac Arrest: A One-Year Follow-Up

A 61-year-old woman survived resuscitation after out-of-hospital cardiac arrest. The heterogeneity of the resulting cognitive impairments and the recovery over a one-year period are presented, highlighting the need for standardized neuropsychological testing even after short cardiac arrests and for effective treatment both out of hospital and in hospital.

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Cobalt Cardiomyopathy Secondary to Hip Arthroplasty: An Increasingly Prevalent Problem

A forty-year-old man experienced worsening heart failure four years following bilateral complicated total hip replacement. His condition was extensively worked up but no underlying pathology was immediately evident. Given the cobalt-chromium alloy component present in the hip arthroplasties, the raised cobalt blood levels, and a fitting clinical picture coupled with radiological findings, the patient underwent right hip revision. Evidence of biotribocorrosion was present on direct visualisation intraoperatively. The patient subsequently experienced symptomatic improvement (NYHA class III to class I) and echocardiography showed recovery of ejection fraction. Cobalt exists as a bivalent and trivalent molecule in circulation and produces a cytotoxicity profile similar to nanoparticles, causing neurological, thyroid, and cardiological pathology. Blood levels are not entirely useful as there is no identifiable conversion factor for levels in whole blood, serum, and erythrocytes which seem to act independently of each other. Interestingly cobalt cardiomyopathy is frequently compounded by other possible causes of cardiomyopathy such as alcohol and a link has been postulated. Definitive treatment is revision of the arthroplasty as other treatments are unproven.

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Urinary Neutrophil Gelatinase-Associated Lipocalin Is Complementary to Albuminuria in Diagnosis of Early-Stage Diabetic Kidney Disease in Type 2 Diabetes

Background. Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). Methods. The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (), without difference in uACR (). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. Conclusions. Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.

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Analyzing Menton Deviation in Posteroanterior Cephalogram in Early Detection of Temporomandibular Disorder

Introduction. Some clinicians believed that mandibular deviation leads to facial asymmetry and it also had a correlation with temporomandibular disorders (TMDs). Posteroanterior (PA) cephalogram was widely reported as a regular record in treating facial asymmetry and craniofacial anomalies. The objective of this study was to analyze the relationship of menton deviation in PA cephalogram with temporomandibular disorders (TMDs) symptoms. Materials and Methods. TMJ function was initially screened based on TMD-DI questionnaire. PA cephalogram of volunteer subjects with TMDs () and without TMDs () with mean age of years was taken. The menton deviation was measured by the distance (mm) from menton point to midsagittal reference (MSR) horizontally, using software digitized measurement, and categorized as asymmetric if the value is greater than 3 mm. The prevalence and difference of menton deviation in both groups were evaluated by unpaired -test. Result. The prevalence of symmetry group showed that 65.9% had no TMDs with mean of 1,815 ± 0,71 mm; in contrast, the prevalence of asymmetry group showed that 95.5% reported TMDs with mean of 3,159 ± 1,053 mm. There was a significant difference of menton deviation to TMDs () in subjects with and without TMDs. Conclusion. There was a significant relationship of menton deviation in PA cephalogram with TMDs based on TMD-DI index.

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Continuous Analog of Accelerated OS-EM Algorithm for Computed Tomography

The maximum-likelihood expectation-maximization (ML-EM) algorithm is used for an iterative image reconstruction (IIR) method and performs well with respect to the inverse problem as cross-entropy minimization in computed tomography. For accelerating the convergence rate of the ML-EM, the ordered-subsets expectation-maximization (OS-EM) with a power factor is effective. In this paper, we propose a continuous analog to the power-based accelerated OS-EM algorithm. The continuous-time image reconstruction (CIR) system is described by nonlinear differential equations with piecewise smooth vector fields by a cyclic switching process. A numerical discretization of the differential equation by using the geometric multiplicative first-order expansion of the nonlinear vector field leads to an exact equivalent iterative formula of the power-based OS-EM. The convergence of nonnegatively constrained solutions to a globally stable equilibrium is guaranteed by the Lyapunov theorem for consistent inverse problems. We illustrate through numerical experiments that the convergence characteristics of the continuous system have the highest quality compared with that of discretization methods. We clarify how important the discretization method approximates the solution of the CIR to design a better IIR method.

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The Anti-Inflammatory Effect of Guchangzhixie-Pill by Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in an Ulcerative Colitis Rat Model

Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases (IBD). Abnormal colonic enterochromaffin (EC) cell hyperplasia and serotonin availability have been described in UC. Guchangzhixie-pill (GCZX-pill), a Chinese herbal formula composed of six herbs, is modified based on a traditional formula (Jiechangyan-pill) for inflammatory and ulcerative gastrointestinal disorders. This study aims to investigate the anti-inflammatory effect and the underlying mechanisms of GCZX-pill on trinitrobenzene sulfonic acid- (TNBS-) induced UC in rats. After orally administrating a GCZX-pill to UC rats for 14 days, the results of the inflammation evaluation, such as disease activity index (DAI), macroscopic score (MS), myeloperoxidase (MPO) activity, and other methods, suggested that the GCZX-pill showed remarkable anti-inflammatory results in UC rats. In addition, the abnormal EC cell numbers, colonic tryptophan hydroxylase (TPH) expression, and serotonin (5-HT) contents in TNBS-induced UC rats were significantly reduced by the GCZX-pill. This data demonstrates that the GCZX-pill can attenuate the inflammation in UC rats and the anti-inflammatory effect of the GCZX-pill may be medicated by reducing colonic EC cell hyperplasia and 5-HT availability.

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Unmet Needs in the Field of Psoriasis: Pathogenesis and Treatment

Abstract

In times of targeted therapies, innovative therapeutics become tools to further unravel the pathogenesis of the treated disease, thus influencing current pathogenetic concepts. Based on such paradigm shifts, the next generation of novel therapeutic targets might be identified. Psoriasis is a good example for the resulting most fruitful dialog between clinical and fundamental research. As a result of this, the key role of Th17 lymphocytes, some of their effector molecules, as well as mediators contributing to their maturation have been identified, many of these being targeted by some of the most effective drugs currently available to treat psoriasis. During this process, it became obvious that major parts of the puzzle remain yet to be uncovered or understood in much more detail. This review will therefore address the search for additional important effector cells other than Th17 lymphocytes, such as neutrophils, monocytes, and mast cells, mediators other than IL-17A, including some other IL-17 isoforms, and trigger factors such as potential autoantigens. This will lead to discussing the next generation of targeted therapies for psoriasis as well as treatment goals. These goals need to comprise both psoriasis as well as its comorbidities, as a comprehensive approach to manage the whole patient with all his health issues is urgently needed. Finally, given the substantial differences in resources available in different parts of the world, the global burden of psoriasis and options on how to care for patients outside developed countries will be assessed.

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Foliar application of aspartic acid lowers cadmium uptake and Cd-induced oxidative stress in rice under Cd stress

Abstract

Cadmium (Cd) contamination of farmland soils is a widespread problem around the globe, and rice (Oryza sativa L.) tends to accumulate more Cd and is considered as one of the major sources of Cd intake in humans, especially consuming rice-derived products. The current study investigated the effects of foliar applied aspartic acid (Asp) on growth parameters, biomass, chlorophyll concentration, gas exchange characteristics, Cd uptake, and antioxidative capacity in the shoots and roots of rice seedlings exposed to Cd stress. For this, 30-day-old rice nursery was transferred in the soil with aged Cd contamination (2.86 mg kg⁻¹). After 2 weeks of growth, different concentrations (0, 10, 15, and 20 mg L⁻¹) of Asp were foliar applied four times with a 7-day interval, and the crop was harvested after 10 weeks of transplanting. Foliar applied Asp increased the plant height, shoot and root dry weight, chlorophyll concentration, and gas exchange parameters, while it reduced the Cd concentrations in both shoots and roots as well as shoot to root Cd translocation factor compared to the control. Foliar application of Asp reduced the malondialdehyde content and electrolyte leakage in rice parts compared to the control in a dose-additive manner. The activities of key antioxidant enzymes increased while peroxidase activity decreased by exogenous Asp. The increase in plant weight and photosynthesis might be due to lower Cd concentrations in plants which may reduce the oxidative stress and also help the plants to minimize direct damage caused by Cd to the photosynthetic organs.

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Performance characteristics of a high-sensitivity cardiac troponin assay using plasma and whole blood samples

Publication date: Available online 5 August 2017
Source:Clinical Biochemistry
Author(s): P. Li, N.S. Enea, R. Zuk, H. Tan, A.H.B. Wu, A.S. Jaffe




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Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the Bnip3 expression

Publication date: 20 September 2017
Source:Gene, Volume 629
Author(s): Rui Xiao, An-Li Xiang, Hong-Bo Pang, Ke-Qiang Liu
AimsRole of hyperoside in protecting cardiomyocytes from ischemia/reperfusion induced injury has been proved. However, possible protecting mechanisms remain unclear. To fix the problem, an essential pro-apoptotic protein Bnip3 was studied in our experiments.Methods and resultsNeonatal rat cardiomyocytes were used and submitted to hypoxia for 8h followed by reoxygenation for 2h to simulate the ischemia/reperfusion injury. Hypoxia/reoxygenation(H/R) induced damage to cardiomyocytes and the protective effect of hyperoside were examined by means of MTT assay. H/R-induced apoptosis was assessed by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) and DNA Ladder assay. mRNA expression of Bnip3 was determined by use of quantitative real-time reverse transcription polymerase chain reaction assay. Protein levels of Bnip3, Bax, Bcl-2 and cleaved caspase-3 were examined using western-blot assay. Our results showed that H/R caused great damage to cardiomyocytes, upregulated the protein expressions of Bnip3, Bax, cleaved caspase3, and decreased the expression of the anti-apoptotic protein of Bcl-2. Whereas, compared with the H/R group, a decrease in activities of Bnip3, Bax, cleaved caspase3, and a promoting expression of Bcl-2 were detected in the H/R goup pretreated with hyperoside.ConclusionIt was concluded in our study that H/R-induced apoptotic effect in cardiomyocytes could be attenuated by hyperoside, and the protective role of hyperoside, if not completely, could be partly through the suppression of the pro-apoptotic gene Bnip3.



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Bm-muted, orthologous to mouse muted and encoding a subunit of the BLOC-1 complex, is responsible for the otm translucent mutation of the silkworm Bombyx mori

Publication date: 20 September 2017
Source:Gene, Volume 629
Author(s): Haokun Zhang, Takashi Kiuchi, Lingyan Wang, Munetaka Kawamoto, Yutaka Suzuki, Sumio Sugano, Yutaka Banno, Susumu Katsuma, Toru Shimada
"Tanaka's mottled translucent" (otm) is a mutation of the silkworm Bombyx mori that exhibits translucent skin during larval stages. We performed positional cloning of the gene responsible for otm and mapped it to a 364-kb region on chromosome 5 that contains 22 hypothetical protein-coding genes. We performed RNA-seq analysis of the epidermis and fat body of otm larvae and determined that the gene BGIBMGA002619 may be responsible for the otm mutation. BGIBMGA002619 encodes the biosynthesis of lysosome-related organelles complex 1 (BLOC-1) subunit 5, whose ortholog is responsible for the Muted mutant in mouse. Accordingly, we named this gene Bm-muted. We discovered that the expression of Bm-muted in the epidermis and fat body of otm mutants was dramatically suppressed compared with the wild type. We determined the nucleotide sequences of the full-length cDNA and genomic region corresponding to Bm-muted and found that a 538-bp long DNA sequence similar to B. mori transposon Organdy was inserted into the 3′ end of the first intron of Bm-muted in two otm strains. The Bm-muted cDNA of otm mutants lacked exon 2, and accordingly generated a premature stop codon in exon 3. In addition, short interfering RNA (siRNA)-mediated knockdown of this gene caused localized partial translucency of larval skin. These data indicate that the mutation in Bm-muted caused the otm-mutant phenotype. We propose that the insertion of Organdy caused a splicing disorder in Bm-muted in the otm mutant, resulting in a null mutation of Bm-muted. This mutation is likely to cause deficiencies in urate granule formation in epidermal cells that result in translucent larval skin.

Graphical abstract

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Lipoid proteinosis: A clinical and molecular study in Egyptian patients

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Hanan H. Afifi, Khalda S. Amr, Angie M.S. Tosson, Tarak A. Hassan, Mennat I. Mehrez, Ghada Y. El-Kamah
Lipoid proteinosis (LP) is an autosomal recessive disorder caused by the loss of function of ECM1 gene. Clinical features include varying degrees of skin thickening, hoarseness of voice and less frequently neuropsychiatric abnormalities.Twelve patients from ten unrelated families with a clinical diagnosis of lipoid proteinosis were enrolled in this study. Extraction of DNA samples of the 12 patients and their parents from peripheral blood by standard methods was performed. Polymerase chain reaction (PCR) amplification of the ECM1 gene was conducted using eight pairs of primers spanning over the 10 exons and splice junctions.Patients exhibited a variety of clinical manifestations with skin affection and hoarseness of voice being the consistent feature. We identified five novel homozygous insertion, small deletion, missense, and splice site mutations as well as two homozygous previously published splice site mutation c.70+1G>C in intron 1 and c.1305-2A>G in intron 8. The specific mutations were: c.10_11insC in exon 1, c.690_691delAG in exon 6, c.734G>A in exon 7, c.1286_1287delAA in exon 8 and c.1393-1G>T in intron 9. The novel mutations c.1393-1G>T and c.10_11insC occurred in three (30%) and two (20%) unrelated patients of the studied families, respectively. Further studies may designate an increased frequency of these mutations among Egyptian LP patients. Identification of pathogenic ECM1 mutations is important for accurate diagnosis and proper genetic counseling.



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The flexible stem hypothesis : evidence from genetic data

Abstract

Phenotypic plasticity, the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions, is widely observed in the wild. It is believed to facilitate evolution and, under the "flexible stem hypothesis", it is thought that an ancestral plastic species can be at the origin of sister lineages with divergent phenotypes fixed by genetic assimilation of alternative morphs. We review here the genetic mechanisms underlying such phenomenon. We show several examples in which the same gene shows transcriptional plasticity in response to environmental factors and divergence of expression within or between species. Thus, the same gene is involved both in the plasticity of a trait and in the evolution of that trait. In a few cases, it can be traced down to cis-regulatory variation in this gene and, in one case, in the very same regulatory sequence whose activity is modulated by the environment. These data are compatible with the "flexible stem hypothesis" and also suggest that the evolution of the plasticity of a trait and the evolution of the trait are not completely uncoupled as they often involve the same locus. Furthermore, the "flexible stem hypothesis" implies that it is possible to canalize initially plastic phenotypes. Several studies have shown that it was possible through modification of chromatin regulation or hormonal signalling/response. Further studies of phenotypic plasticity in an evolutionary framework are needed to see how much the findings described in this review can be generalized.

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Copyright-Page

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Contributors

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Contents

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Forthcoming Issues

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Transplantation

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Aman Mahajan, Christopher Wray




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Overview of Immunosuppressive Therapy in Solid Organ Transplantation

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Curtis D. Holt

Teaser

Mechanisms of rejection, new pharmacologic approaches, and genomic medicine are major foci for current research in transplantation. It is hoped that these new agents and personalized immunosuppression will provide for less toxic regimens that are effective in preventing both acute and chronic allograft rejection. Until new agents are available, practitioners must use various combinations of currently approved agents to find the best regimens for improved long-term outcomes.


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Dental Researchers Awarded NIH Grant for Microbiome Research to Identify Biomarkers for Tongue Cancer - NYU News (press release)

NYU News (press release)

Dental Researchers Awarded NIH Grant for Microbiome Research to Identify Biomarkers for Tongue Cancer NYU News (press release) Researchers at New York University College of Dentistry's (NYU Dentistry) Bluestone Center for Clinical Research have been awarded a two-year National Institutes of Health (NIH) grant to develop biomarkers for tongue cancer, a subset of oral cancers ...

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Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer

Investigating the RNA-RNA interaction involving in the initiation and progression of non-small cell lung cancer (NSCLC) may provide promising diagnostic and targeted therapeutic strategies. Here, we showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3' UTR-dependent manners. And miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. Intriguingly, we initially uncovered that PCNX-3' UTR promotes cell growth, proliferation and cell cycle progression, and suppresses apoptosis of lung cancer cells, which is consistent with the oncogenic activity of Skp2-3' UTR.

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Protein glycosylation in viral hepatitis-related HCC: Characterization of heterogeneity, biological roles, and clinical implications

Protein glycosylation is one of the most frequent and well-known posttranslational modifications, playing important roles in physiopathological processes. Glycosylation is catalyzed by enzymatic additions of heterogeneous glycans with specific linkage of monosaccharides and, in a preformed fashion, to specific amino acids within glycoproteins. Altered glycan macroheterogeneity and microheterogeneity have been reported in glycoproteins produced mainly by the liver, facilitating tumorigenesis, progression, and metastasis.

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Accuracy and reproducibility of a newly developed tool for volume measurements of the arm using 3D stereophotogrammetry

Lymph edema of the arm is a common complication after breast cancer treatment. To evaluate lymph edema volume and treatment outcome, an easy to use, objective quantification method of arm volume is necessary. Most of the times, water displacement is used to measure arm volume, as it is an easy and robust method that can be performed at any place with some simple equipment. However, when using water displacement, no exact localization of volume differences can be seen. To accurately measure hand and forearm volume separately, an in house developed device was made for accurate landmark placement.

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Risk of Major Limb Amputation in diabetic foot ulcer and accompanying disease: A meta-analysis

Limb amputation in diabetic patients raises important issues regarding lower quality of life and survival rates. This meta-analysis is aimed to identify predictive factors accompanying diseases with high major amputation rates in diabetic patients.

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Assessing the Effort Associated with Teaching Residents

Intraoperative resident education is an integral mission of academic medical centers and serves as the basis for training the next generation of surgeons. The actual effort associated with teaching residents, as it pertains to additional operative time, is unknown. Using a large validated multi-institutional dataset, this study aims to quantify the effect on operative time of having a resident present in common plastic surgery procedures. Future directions for developing standardized methods to record and report teaching time are proposed, which can help inform prospective studies.

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Invited Commentary: Analysis of Risk Factors Associated with Unplanned Re-Operations following Pediatric Plastic Surgery

Jubbal et al. have used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric database to identify parameters associated with an increased likelihood of unplanned reoperation following plastic surgery in children under 18 years of age.1 To interpret this study, it is important to understand a little of the background to the database from which it was drawn.

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Factors influencing adsorption and desorption of trimethoprim on marine sediments: mechanisms and kinetics

Abstract

Adsorption-desorption behavior of ionic antibiotics in natural aquatic environment is complex, especially in coastal or estuary area where influencing factors such as pH and salinity usually varied in a wide range. In this study, batch-type and stirred flow chamber (SFC) experiments were carried out to simulate the sorption-desorption behavior of trimethoprim (TMP) in seawater-sediment system. Equilibrium and kinetic modeling were carried out to determine the rate and extent of TMP sorption on two marine sediments with different properties. Sediment BHB (K _d , 6.40 L kg⁻¹) has a greater sorption capacity compared with sediment LZB (K _d , 3.40 L kg⁻¹), which is related to the higher content of organic carbon and clay of sediment BHB. Adsorption of TMP varied in the pH range of 6.9 to 8.1 with maximum adsorption at pH 7.4. Increasing salinity and presence of phosphate and nitrate led to decreased TMP sorption. Attenuated total reflection Fourier transform infrared (ATR-FTIR) analysis demonstrated the formation of hydrogen bond between TMP and marine sediments. Adsorption of TMP on marine sediments was a non-equilibrium process that can be described with second-order kinetic model. Our analysis suggested that chemical non-equilibrium was the rate controlling process and intraparticle diffusion was also involved in TMP adsorption. A moderate desorption percentage (16.4–22.8% for LZB and 32.5–42.0%for BHB) was observed. Overall, the results showed that environmental factors and time-dependent processes need to be considered in modeling the fate and transport of TMP in coastal/estuarine waters.

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Val Kilmer's absence from events fuels fear for his health - Page Six

Page Six

Val Kilmer's absence from events fuels fear for his health Page Six Coincidentally, Douglas himself admitted in 2013 to lying about cancer. Douglas discovered before a press tour for "Wall Street: Money Never Sleeps" that he had tongue cancer, but told the public he had throat cancer because the prognosis for tongue ...

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A novel decision support system for the interpretation of remote sensing big data

Abstract

Applications of remote sensing (RS) data cover several fields such as: cartography, surveillance, land-use planning, archaeology, environmental studies, resources management, etc. However, the amount of RS data has grown considerably due to the increase of aerial and satellite sensors. With this continuous increase, the necessity of having automated tools for the interpretation and analysis of RS big data is clearly obvious. The manual interpretation becomes a time consuming and expensive task. In this paper, a novel tool for interpreting and analyzing RS big data is described. The proposed system allows knowledge gathering for decision support in RS fields. It helps users easily make decisions in many fields related to RS by providing descriptive, predictive and prescriptive analytics. The paper outlines the design and development of a framework based on three steps: RS data acquisition, modeling, and analysis & interpretation. The performance of the proposed system has been demonstrated through three models: clustering, decision tree and association rules. Results show that the proposed tool can provide efficient decision support (descriptive and predictive) which can be adapted to several RS users' requests. Additionally, assessing these results show good performances of the developed tool.

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Robotic device-assisted knee extension training during the early postoperative period after opening wedge high tibial osteotomy: a case report

Maintenance or restoration of a good range of motion of the knee is one of the most important outcomes following knee surgery. According to previous studies, opening wedge high tibial osteotomy enables better ...

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Irish scans may have to be repeated due to a computer glitch

Thousands of medical imaging scans in the Republic of Ireland may have to be...

Read more on AuntMinnieEurope.com

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Irish get rave reviews for plain-film checklist

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Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review

Abstract

Purpose

The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.

Methods

Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.

Results

A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.

Conclusion

This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.

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Mathematical model for the transport of fluoroquinolone and its resistant bacteria in aquatic environment

Abstract

Development of antibiotic resistance in environmental bacteria is a direct threat to public health. Therefore, it becomes necessary to understand the fate and transport of antibiotic and its resistant bacteria. This paper presents a mathematical model for spatial and temporal transport of fluoroquinolone and its resistant bacteria in the aquatic environment of the river. The model includes state variables for organic matter, fluoroquinolone, heavy metals, and susceptible and resistant bacteria in the water column and sediment bed. Resistant gene is the factor which makes bacteria resistant to a particular antibiotic and is majorly carried on plasmids. Plasmid-mediated resistance genes are transferable between different bacterial species through conjugation (horizontal resistance transfer). This model includes plasmid dynamics between susceptible and resistant bacteria by considering the rate of horizontal resistance gene transfer among bacteria and the rate of losing resistance (segregation). The model describes processes which comprise of advection, dispersion, degradation, adsorption, diffusion, settling, resuspension, microbial growth, segregation, and transfer of resistance genes. The mathematical equations were solved by using numerical methods (implicit-explicit scheme) with appropriate boundary conditions. The development of the present model was motivated by the fact that the Musi River is heavily impacted by antibiotic pollution which led to the development of antibiotic resistance in its aquatic environment. The model was simulated for hypothetical pollution scenarios to predict the future conditions under various pollution management alternatives. The simulation results of the model for different cases show that the concentration of antibiotic, the concentration of organic matter, segregation rate, and horizontal transfer rate are the governing factors in the variation of population density of resistant bacteria. The treatment of effluents for antibiotics might be costly for the bulk drug manufacturing industries, but the guidelines can be made to reduce the organic matter which can limit the growth rate of microbes and reduce the total microbial population in the river. The reduction in antibiotic concentration can reduce the selection pressure on bacteria and can limit the population of resistant culture and its influence zone in the river stretch; however, complete removal of antibiotics may not result in complete elimination of antibiotic-resistant bacteria.

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Engineered silica nanoparticles alleviate the detrimental effects of Na + stress on germination and growth of common bean ( Phaseolus vulgaris )

Abstract

During the past 10 years, exploiting engineered nanoparticles in agricultural sector has been rapidly increased. Nanoparticles are used to increase the productivity of different crops particularly under biotic and abiotic stresses. This study aims to test the ability of nanosilica (NS) to ameliorate the detrimental impact of Na⁺ with different concentrations on the seed germination and the growth of common bean seedlings. Five doses of Na⁺ have been prepared from NaCl, i.e., 1000, 2000, 3000, 4000, and 5000 mg L⁻¹, and distilled water was applied as a control. Seeds and seedlings were treated with three different NS concentrations (100, 200, and 300 mg L⁻¹). The results proved that Na⁺ concentrations had detrimental effects on all measured parameters. However, treating seeds and seedlings with NS improved their growth and resulted in higher values for all measurements. For instance, the addition of 300 mg L⁻¹ NS leads to an increase of the final germination percentage, vigor index, and germination speed for seeds irrigated with 5000 mg Na⁺ L⁻¹ by 19.7, 80.7, and 22.6%, respectively. Although common bean seedlings could not grow at the highest level of Na⁺, fortification seedlings with NS helped them to grow well under 5000 mg L⁻¹ of Na⁺. An increase of 11.1 and 23.1% has been measured for shoot and root lengths after treating seedlings with 300 mg L⁻¹ NS under irrigation with 5000 mg Na⁺ L⁻¹ solutions, and also at the same treatment, shoot and root dry masses are enhanced by 110.9 and 328.0%, respectively. These results proved the importance of using NS to relieve the detrimental effects of Na⁺-derived salinity. This finding could be reinforced by low Na content which was measured in plant tissues after treating seedlings with 300 mg L⁻¹ of NS.

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Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review

Abstract

Purpose

The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.

Methods

Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.

Results

A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.

Conclusion

This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.

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Long-term treatment with leuprorelin for spinal and bulbar muscular atrophy: natural history-controlled study

Objective

To evaluate the prognosis and progression of spinal and bulbar muscular atrophy (SBMA), a rare X-linked motor neuron disorder caused by trinucleotide repeat expansion in the AR (androgen receptor) gene, after long-term androgen suppression with leuprorelin acetate treatment.

Methods

In the present natural history-controlled study, 36 patients with SBMA treated with leuprorelin acetate for up to 84 months (leuprorelin acetate-treated group; LT group) and 29 patients with SBMA with no specific treatment (non-treated group; NT group) were analysed. Disease progression was evaluated by longitudinal quantitative assessment of motor functioning using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the modified Norris score. In addition, we selected two major clinical endpoint events, namely the occurrence of pneumonia requiring hospitalisation and death, to evaluate disease prognosis following long-term leuprorelin acetate treatment.

Results

In our analysis of the longitudinal disease progression using the random slope model, we observed a significant difference in the ALSFRS-R total score, the Limb Norris Score, and the Norris Bulbar Score (p=0.005, 0.026 and 0.020, respectively), with the LT group exhibiting a slower per-12-months decline compared with the NT group. As for the event analysis, the prognosis of the LT group was better in comparison to the NT group as for the event-free survival period (p=0.021).

Conclusion

Long-term treatment with leuprorelin acetate appears to delay the functional decline and suppress the incidence of pneumonia and death in subjects with SBMA.

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Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency

Introduction

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised.

Objectives

To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy.

Methods

Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified.

Results

34 patients were identified (median age 55 years, range 36–78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0–0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation.

Conclusions

An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance.

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Time for a Change in How New Antibiotics are Reimbursed: Development of an Insurance Framework for Funding New Antibiotics based on a Policy of Risk Mitigation

Publication date: Available online 5 August 2017
Source:Health Policy
Author(s): Adrian Towse, Christopher K. Hoyle, Jonathan Goodall, Mark Hirsch, Jorge Mestre-Ferrandiz, John H. Rex
Healthcare systems depend on the availability of new antibiotics. However, there is a lack of treatments for infections caused by multidrug resistant (MDR) pathogens and a weak development pipeline of new therapies. One core challenge to the development of new antibiotics targeting MDR pathogens is that expected revenues are insufficient to drive long-term investment. In the USA and Europe, financial incentives have focussed on supporting R&D, reducing regulatory burden, and extending market exclusivity. Using resistance data to estimate global revenues, we demonstrate that the combined effects of these incentives are unlikely to rekindle investment in antibiotics. We analyse two supplemental approaches: a commercial incentive (a premium price model) and a new business model (an insurance model). A premium price model is familiar and readily implemented but the required price and local budget impact is highly uncertain and sensitive to cross-sectional and longitudinal variation in prevalence of antibiotic resistance. An insurance model delivering risk mitigation for payers, providers and manufacturers would provide an incentive to drive investment in the development of new antibiotics while also facilitating antibiotic conservation. We suggest significant efforts should be made to test the insurance model as one route to stimulate investment in novel antibiotics.



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Applying the health action process approach to bicycle helmet use and evaluating a social marketing campaign

Background

Bicycle injuries are of concern in Canada. Since helmet use was mandated in 1996 in the province of British Columbia, Canada, use has increased and head injuries have decreased. Despite the law, many cyclists do not wear a helmet. Health action process approach (HAPA) model explains intention and behaviour with self-efficacy, risk perception, outcome expectancies and planning constructs. The present study examines the impact of a social marketing campaign on HAPA constructs in the context of bicycle helmet use.

Method

A questionnaire was administered to identify factors determining helmet use. Intention to obey the law, and perceived risk of being caught if not obeying the law were included as additional constructs. Path analysis was used to extract the strongest influences on intention and behaviour. The social marketing campaign was evaluated through t-test comparisons after propensity score matching and generalised linear modelling (GLM) were applied to adjust for the same covariates.

Results

400 cyclists aged 25–54 years completed the questionnaire. Self-efficacy and Intention were most predictive of intention to wear a helmet, which, moderated by planning, strongly predicted behaviour. Perceived risk and outcome expectancies had no significant impact on intention. GLM showed that exposure to the campaign was significantly associated with higher values in self-efficacy, intention and bicycle helmet use.

Conclusion

Self-efficacy and planning are important points of action for promoting helmet use. Social marketing campaigns that remind people of appropriate preventive action have an impact on behaviour.

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Association between childhood health, socioeconomic and school-related factors and effort-reward imbalance at work: a 25-year follow-up study

Objectives

Stress pathways can have origins in childhood, but few early predictors have been explored in relation to adult job stress. This study examined whether childhood school, health or socioeconomic factors were associated with adult job stress.

Methods

Data came from the Childhood Determinants of Adult Health study that began in 1985 with children aged 7-15 years who reported effortreward imbalance (ERI) scales at ages 31-41 years. Linear regression assessed the association between childhood factors and adult ERI adjusted for age and socioeconomic position (SEP) in childhood and adulthood.

Results

There were between 999 and 1390 participants in each analysis. Lower adulthood ERI, indicating less job stress, was predicted by several school-related factors in men. For example, each higher category of learner self-concept was associated with a 19% (95% CI – 32% to 6%) reduction in adult ERI, and each unit increase in academic attainment was associated with a 15% (95% CI –28% to 3%) reduction in adult ERI. Childhood health was associated with adult ERI. For example, in women, overweight children had 14% (95% CI 5% to 22%) higher adult ERI scores compared with healthy weight children, and each unit of negative affect was associated with 2% (95% CI 1% to 4%) increase in adult ERI. Adult SEP had no effect on these associations for men but explained some of the effect in women. Childhood SEP had inconsistent associations with adult ERI.

Conclusion

Our findings suggest that a range of childhood socioeconomic, school- and health-related factors might contribute to the development of job stress in adulthood.

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Biomass smoke exposure as an occupational risk: cross-sectional study of respiratory health of women working as street cooks in Nigeria

Objective

Little is known about respiratory health of women who are occupationally exposed to biomass smoke outside their homes. This study reports the exposure and respiratory health of street cooks in Ile-Ife, Nigeria.

Methods

We assessed exposure to biomass smoke by questionnaire in 188 street cooks and 197 control women and by personal diffusive samplers to quantify volatile organic compounds (VOCs) in a subsample of the women. Respiratory symptoms were assessed by a standardised questionnaire, and pulmonary function was assessed by spirometry before and after bronchodilation. Regression analysis was conducted to compare the outcome between the two groups.

Results

The study included 188 women (median age 40, IQR 30–50 years) who had worked as street cooks for a median of 7 years (IQR 3–15 years) and 197 control women with similar demographics. Benzene concentration in passive samplers worn by the street cooks was significantly higher compared with controls (median (IQR) 119.3 (82.7–343.7) µg/m³ vs 0.0 (0.0–51.2) µg/m³, p<0.001). The odds of reported respiratory symptoms were significantly higher among the street cooks than controls: cough (adjusted OR 4.4, 95% CI 2.2 to 8.5) and phlegm (adjusted OR 3.9, 95% CI 1.5 to 7.3). The street cooks also had higher odd of airway obstruction as measured by forced expiratory volume in 1 s/forced vital capacity <0.7: 11% 3% (adjusted OR of 3.3 (95% CI 1.3 to 8.7)).

Conclusions

This study provides evidence of adverse respiratory effects among street cooks using biomass fuels.

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Effect of reduced use of organic solvents on disability pension in painters

Objective

To investigate whether the decreased use of paints based on organic solvents has caused a decreased risk for neuropsychiatric disorders in painters by studying their incidence in disability pensions.

Methods

The incidence of disability pension in Swedish painters who had participated in health examinations between 1971 and 1993 was studied through linkage with Swedish registers of disability pension over 1971–2010 and compared with the incidence in other construction workers as woodworkers, concrete workers and platers. When phasing out began in the 1970s, about 40% of paints were based on organic solvents and it had decreased to 4% in 1990s. The analysis was adjusted for age, time period, body mass index and smoking.

Results

The painters (n=23 065) had an increased risk of disability pension due to neurological diagnosis (n=285, relative risk (RR) 1.92, 95% CI 1.67 to 2.20) and psychiatric diagnosis (n=632, RR=1.61, 95 % CI 1.42 to 1.82). For neurological disorders there was a time trend with a continuously decreasing risk from 1980 onwards, but there was no such trend for psychiatric disorders.

Conclusions

High exposure to organic solvents increased the risk for disability pension in neurological disorders, and the risk decreased when the use of organic solvents decreased. The painters also had an increased risk of disability pension due to psychiatric disorders, but the causes have to be further investigated.

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Can an observational pain assessment tool improve time to analgesia for cognitively impaired older persons? A cluster randomised controlled trial

Objective

The primary objective of the study was to measure the impact of an observational pain assessment dementia tool on time from ED arrival to first dose of analgesic medicine.

Methods

A multisite cluster randomised controlled trial was conducted to test the Pain Assessment in Advanced Dementia (PAINAD) tool. Patients aged 65 years or older suspected of a long bone fracture were screened for cognitive impairment using the Six-Item Screening (SIS) tool. Patients scoring 4 or less on SIS (intervention sites) were assessed for pain using PAINAD. Control sites, assessed pain using standard methods. The primary outcome was time to first dose of analgesia and was analysed on an intention-to-treat basis with a sensitivity analysis.

Results

We enrolled 602 patients, of which 323 (54%) were at intervention sites (n=4). The median time to analgesia was 82 min (IQR 45–151 min). There was no statistically significant difference in median time to analgesia for intervention 83 (IQR 48–158 min) and non-intervention 82 min (IQR 41–147 min) sites (p=0.414). After adjusting for age, fracture type, arrival mode and triage category, there remained no significant difference in time to analgesia (HR 0.97, 95% CI 0.80 to 1.17, p=0.74). Of the 602 patients enrolled, 273 actually had cognitive impairment. A sensitivity analysis demonstrated patients at intervention sites received analgesia 13 min sooner (90 vs 103 min, p=0.91).

Conclusion

Use of the PAINAD was not associated with a shorter time to analgesia, although there was a clinically important but non-significant improvement in the cognitively impaired patient group. Further research is needed to address this clinically important and complex issue.

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Nursing home Facebook reviews: who has them, and how do they relate to other measures of quality and experience?

Background

The growing use of social media creates opportunities for patients and families to provide feedback and rate individual healthcare providers. Whereas previous studies have examined this emerging trend in hospital and physician settings, little is known about user ratings of nursing homes (NHs) and how these ratings relate to other measures of quality.

Objective

To examine the relationship between Facebook user-generated NH ratings and other measures of NH satisfaction/experience and quality.

Methods

This study compared Facebook user ratings of NHs in Maryland (n=225) and Minnesota (n=335) to resident/family satisfaction/experience survey ratings and the Centers for Medicare and Medicaid (CMS) 5-star NH report card ratings.

Results

Overall, 55 NHs in Maryland had an official Facebook page, of which 35 provided the opportunity for users to rate care in the facility. In Minnesota, 126 NHs had a Facebook page, of which 78 allowed for user ratings. NHs with higher aid staffing levels, not affiliated with a chain and located in higher income counties were more likely to have a Facebook page. Facebook ratings were not significantly correlated with the CMS 5-star rating or survey-based resident/family satisfaction ratings.

Conclusions

Given the disconnect between Facebook ratings and other, more scientifically grounded measures of quality, concerns about the validity and use of social media ratings are warranted. However, it is likely consumers will increasingly turn to social media ratings of NHs, given the lack of consumer perspective on most state and federal report card sites. Thus, social media ratings may present a unique opportunity for healthcare report cards to capture real-time consumer voice.

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Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations

Background

There are many single-gene causes of steroid-resistant nephrotic syndrome (SRNS) and the list continues to grow rapidly. Prompt comprehensive diagnostic testing is key to realising the clinical benefits of a genetic diagnosis. This report describes a bespoke-designed, targeted next-generation sequencing (NGS) diagnostic gene panel assay to detect variants in 37 genes including the ability to identify copy number variants (CNVs).

Methods

This study reports results of 302 patients referred for SRNS diagnostic gene panel analysis. Phenotype and clinical impact data were collected using a standard proforma. Candidate variants detected by NGS were confirmed by Sanger sequencing/Multiplex Ligation-dependent Probe Amplification with subsequent family segregation analysis where possible.

Results

Clinical presentation was nephrotic syndrome in 267 patients and suspected Alport syndrome (AS) in 35. NGS panel testing determined a likely genetic cause of disease in 44/220 (20.0%) paediatric and 10/47 (21.3%) adult nephrotic cases, and 17/35 (48.6%) of haematuria/AS patients. Of 71 patients with genetic disease, 32 had novel pathogenic variants without a previous disease association including two with deletions of one or more exons of NPHS1 or NPHS2.

Conclusion

Gene panel testing provides a genetic diagnosis in a significant number of patients presenting with SRNS or suspected AS. It should be undertaken at an early stage of the care pathway and include the ability to detect CNVs as an emerging mechanism for genes associated with this condition. Use of clinical genetic testing after diagnosis of SRNS has the potential to stratify patients and assist decision-making regarding management.

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A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct

Background

Enlargement of the vestibular aqueduct (EVA) is the most common radiological abnormality in children with sensorineural hearing loss. Mutations in coding regions and splice sites of the SLC26A4 gene are often detected in Caucasians with EVA. Approximately one-fourth of patients with EVA have two mutant alleles (M2), one-fourth have one mutant allele (M1) and one-half have no mutant alleles (M0). The M2 genotype is correlated with a more severe phenotype.

Methods

We performed genotype–haplotype analysis and massively parallel sequencing of the SLC26A4 region in patients with M1 EVA and their families.

Results

We identified a shared novel haplotype, termed CEVA (Caucasian EVA), composed of 12 uncommon variants upstream of SLC26A4. The presence of the CEVA haplotype on seven of ten 'mutation-negative' chromosomes in a National Institutes of Health M1 EVA discovery cohort and six of six mutation-negative chromosomes in a Danish M1 EVA replication cohort is higher than the observed prevalence of 28 of 1006 Caucasian control chromosomes (p<0.0001 for each EVA cohort). The corresponding heterozygous carrier rate is 28/503 (5.6%). The prevalence of CEVA (11 of 126) is also increased among M0 EVA chromosomes (p=0.0042).

Conclusions

The CEVA haplotype causally contributes to most cases of Caucasian M1 EVA and, possibly, some cases of M0 EVA. The CEVA haplotype of SLC26A4 defines the most common allele associated with hereditary hearing loss in Caucasians. The diagnostic yield and prognostic utility of sequence analysis of SLC26A4 exons and splice sites will be markedly increased by addition of testing for the CEVA haplotype.

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Single-molecule imaging and manipulation of biomolecular machines and systems

Publication date: Available online 5 August 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Ryota Iino, Tatsuya Iida, Akihiko Nakamura, Ei-ichiro Saita, Huijuan You, Yasushi Sako
BackgroundBiological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration.Scope of ReviewWe provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems.Major ConclusionsSingle-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines.General SignificanceQuantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: "What is life?" This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato



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Post-translational modifications of the mitochondrial F1FO-ATPase

Publication date: Available online 4 August 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Salvatore Nesci, Fabiana Trombetti, Vittoria Ventrella, Alessandra Pagliarani
BackgroundThe mitochondrial F1FO-ATPase has the main role in synthesizing most of ATP, thus providing energy to living cells, but it also works in reverse and hydrolyzes ATP, depending on the transmembrane electrochemical gradient. Within the same complex the vital role of the enzyme of life coexists with that of molecular switch to trigger programmed cell death. The two-faced vital/lethal role makes the enzyme complex an intriguing biochemical target to fight pathogens resistant to traditional therapies and diseases linked to mitochondrial dysfunctions. A variety of post-translational modifications (PTMs) of selected F1FO-ATPase aminoacids have been reported to affect the enzyme function.Scope of reviewBy reviewing the known PTMs of aminoacid side chains of both F1 and FO sectors according to the most recent advances, the main aim is to highlight how local chemical changes may constitute the molecular key leading to pathological or physiological events.Major conclusionsPTMs represent the chemical tool to modulate the F1FO-ATPase activity in response to different stimuli. Some PTMs are required to ensure the enzyme catalysis or, conversely, to inactivate the enzyme function. Each covalent modification of the F1FO-ATPase, which occur in response to local changes, is the result of a selective molecular mechanism which, by translating a chemical modification into a biochemical effect, guarantees the enzyme tuning under changing conditions.General significanceOnce highlighted how the molecular mechanism works, some PTMs may be exploited to modulate the effect of drugs targeting the enzyme complex or constitute promising tools for F1FO-ATPase-targeted therapeutic strategies.

Graphical abstract

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Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N-glycans in aggressive prostate cancer cells

Publication date: Available online 4 August 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Ganapati Bhat, Vishwanath-Reddy Hothpet, Ming-Fong Lin, Pi-Wan Cheng
BackgroundThere is a pressing need for biomarkers that can distinguish indolent from aggressive prostate cancer to prevent over-treatment of patients with indolent tumor.MethodsGolgi targeting of glycosyltransferases was characterized by confocal microscopy after knockdown of GM130, giantin, or both. N-glycans on a trans-Golgi enzyme β4galactosyltransferase-1 isolated by immunoprecipitation from androgen-sensitive and independent prostate cancer cells were determined by matrix-assisted laser desorption-time of flight-mass spectrometry. In situ proximity ligation assay was employed to determine co-localization of α-mannosidase IA, an enzyme required for processing Man8GlcNAc2 down to Man5GlcNAc2 to enable synthesis of complex-type N-glycans, with giantin, GM130, and GRASP65, and trans-Golgi glycosyltransferases with high mannose N-glycans terminated with α3-mannose.ResultsDefective giantin in androgen-independent prostate cancer cells results in a shift of Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65. Consequently, trans-Golgi enzymes and cell surface glycoproteins acquire high mannose N-glycans, which are absent in cells with functional giantin. In situ proximity ligation assays of co-localization of α-mannosidase IA with GM130 and GRASP65, and trans-Golgi glycosyltransferases with high mannose N-glycans are negative in androgen-sensitive LNCaP C-33 cells but positive in androgen-independent LNCaP C-81 and DU145 cells, and LNCaP C-33 cells devoid of giantin.ConclusionIn situ proximity ligation assays of Golgi localization of α-mannosidase IA at giantin versus GM130-GRASP65 site, and absence or presence of N-glycans terminated with α3-mannose on trans-Golgi glycosyltransferases may be useful for distinguishing indolent from aggressive prostate cancer cells.



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