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Book Review: Microsurgery of fie Skull Base Microsurgery of fie Skull Base by Fisch UGO , and Mattox Douglas . 670 pages with illustrations. Georg Thieme Verlag, Stuttgart , 1988 . $168.00 .
Otolaryngol Head Neck Surg. 1991 Jun;104(6):897
Authors: Eisele DW, Willis R
PMID: 28791899 [PubMed]
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Book Review: Headache Headache by Raskin Neil Hugh , MD. 396 pages. 2nd ed . Churchill Livingstone, Inc. , New York , 1988 . $49.00.
Otolaryngol Head Neck Surg. 1991 Jun;104(6):895-896
Authors: Eisele DW, Pratt LW
PMID: 28791902 [PubMed]
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Book Review: Guide to Dental Problems for Physicians and Surgeons Guide to Dental Problems for Physicians and Surgeons edited by Thaller Seth R. and Montgomery William W. . 369 pages with illustrations. Williams & Wilkins, Baltimore , 1988 . $68.95 .
Otolaryngol Head Neck Surg. 1991 Jun;104(6):895
Authors: Eisele DW, Medders RG
PMID: 28791901 [PubMed]
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Book Review: Physiology of the Ear Physiology of the Ear edited by John A.E. and Santos-Sacchi J. . 518 pages. Raven Press , New York , 1988 . $99.00 .
Otolaryngol Head Neck Surg. 1991 Jun;104(6):897-898
Authors: Eisele DW, Neal GD
PMID: 28791900 [PubMed]
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Book Review: MCQs in Otolaryngology and Head and Neck Surgery MCQs in Otolaryngology and Head and Neck Surgery by Lancer Jack M. and Jones Andrew S. . 162 pages. Butterworth, London , 1988 . $29.95 .
Otolaryngol Head Neck Surg. 1991 Jun;104(6):896
Authors: Eisele DW, Eisele DW
PMID: 28791898 [PubMed]
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Book Review: Hearing-impaired Children: A Guide for Concerned Parents and Professionals Hearing-impaired Children: A Guide for Concerned Parents and Professionals by Bevan Richard C. . 188 pages. Thomas Charles C. , Springfield, Ill., 1988 . $32.75 .
Otolaryngol Head Neck Surg. 1991 Jun;104(6):896
Authors: Eisele DW, Catlin FI
PMID: 28791897 [PubMed]
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I am a transgender woman who has lived in my new identity for over two years. My GP was very supportive and referred me to a gender identity clinic, where I have been seen and diagnosed as having...
The number of patients on waiting lists for elective surgery at NHS hospitals in England has passed four million for the first time in 10 years, official figures show.1Service leaders and experts...
The death rate among people admitted to hospital with heart failure in England and Wales fell to 8.9% in 2015-16, down from 9.6% the previous year, saving about 500 lives, show figures from the...
| A Hard Road Mountain View Voice (blog) I want to share an excerpt from another new book of mine: A Hard Road It's a story of cancer survival for patients and caregivers.We hope it will help you as you travel your own hard roads. Locke was diagnosed with tonsil cancer that had spread to ... |
| The Sunshine Coast Daily | Community forum helps locals living with head and neck cancer The Sunshine Coast Daily More than 740 Queenslanders are diagnosed with head and neck cancer each year. To reach out to locals affected, Cancer Council Queensland will host a free information session this month. Understanding head and neck cancers will be held on ... |
IJMS, Vol. 18, Pages 1756: Galectin-3 Performance in Histologic a Cytologic Assessment of Thyroid Nodules: A Systematic Review and Meta-Analysis
International Journal of Molecular Sciences doi: 10.3390/ijms18081756
Authors: Pierpaolo Trimboli Camilla Virili Francesco Romanelli Anna Crescenzi Luca Giovanella
The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was conducted by combinations of the terms thyroid and Gal-3. Initially, 545 articles were found and, after their critical review, 52 original papers were finally included. They reported 8172 nodules with histologic evaluation of Gal-3, of which 358 with also preoperative FNAC Gal-3 assessment. At histology, Gal-3 sensitivity was 87% (95% confidence intervals [CI] from 86% to 88%), and specificity 87% (95% CI from 86% to 88%); in both cases, we found heterogeneity (I2 85% and 93%, respectively) and significant publication bias (p < 0.001). The pooled rate of positive Gal-3 at fine needle aspiration (FNAC) among cancers with histologically proven Gal-3 positivity was 94% (95% CI from 89% to 97%), with neither heterogeneity (I2 14.5%) nor bias (p = 0.086). These data show high reliability of Gal-3 for thyroid cancer at histology, while its sensitivity on FNAC samples is lower. The limits of cytologic preparations and interpretation of Gal-3 results have to be solved.
IJMS, Vol. 18, Pages 1744: Electronegative Low-Density Lipoprotein L5 Impairs Viability and NGF-Induced Neuronal Differentiation of PC12 Cells via LOX-1
International Journal of Molecular Sciences doi: 10.3390/ijms18081744
Authors: Jiz-Yuh Wang Chiou-Lian Lai Ching-Tien Lee Chen-Yen Lin
There have been striking associations of cardiovascular diseases (e.g., atherosclerosis) and hypercholesterolemia with increased risk of neurodegeneration including Alzheimer's disease (AD). Low-density lipoprotein (LDL), a cardiovascular risk factor, plays a crucial role in AD pathogenesis; further, L5, a human plasma LDL fraction with high electronegativity, may be a factor contributing to AD-type dementia. Although L5 contributing to atherosclerosis progression has been studied, its role in inducing neurodegeneration remains unclear. Here, PC12 cell culture was used for treatments with human LDLs (L1, L5, or oxLDL), and subsequently cell viability and nerve growth factor (NGF)-induced neuronal differentiation were assessed. We identified L5 as a neurotoxic LDL, as demonstrated by decreased cell viability in a time- and concentration-dependent manner. Contrarily, L1 had no such effect. L5 caused cell damage by inducing ATM/H2AX-associated DNA breakage as well as by activating apoptosis via lectin-like oxidized LDL receptor-1 (LOX-1) signaling to p53 and ensuring cleavage of caspase-3. Additionally, sublethal L5 long-termly inhibited neurite outgrowth in NGF-treated PC12 cells, as evidenced by downregulation of early growth response factor-1 and neurofilament-M. This inhibitory effect was mediated via an interaction between L5 and LOX-1 to suppress NGF-induced activation of PI3k/Akt cascade, but not NGF receptor TrkA and downstream MAPK pathways. Together, our data suggest that L5 creates a neurotoxic stress via LOX-1 in PC12 cells, thereby leading to impairment of viability and NGF-induced differentiation. Atherogenic L5 likely contributes to neurodegenerative disorders.
IJMS, Vol. 18, Pages 1743: Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan
International Journal of Molecular Sciences doi: 10.3390/ijms18081743
Authors: Mitchell Sullivan Silvia Nitschke Martin Steup Berge Minassian Felix Nitschke
Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen. Recent data clearly show that an abnormal glycogen chain length distribution, but neither hyperphosphorylation nor impairment of general autophagy, strictly correlates with glycogen accumulation and the presence of LBs. This review summarizes results obtained with patients, mouse models, and cell lines and consolidates apparent paradoxes in the LD literature. Based on the growing body of evidence, it proposes that LD is predominantly caused by an impairment in chain-length regulation affecting only a small proportion of the cellular glycogen. A better grasp of LD pathogenesis will further develop our understanding of glycogen metabolism and structure. It will also facilitate the development of clinical interventions that appropriately target the underlying cause of LD.
IJMS, Vol. 18, Pages 1749: Treatment of the First Acute Relapse Following Therapeutic Plasma Exchange in Formerly Glucocorticosteroid-Unresponsive Multiple Sclerosis Patients—A Multicenter Study to Evaluate Glucocorticosteroid Responsiveness
International Journal of Molecular Sciences doi: 10.3390/ijms18081749
Authors: Johannes Ehler Stephan Blechinger Paulus Rommer Sebastian Koball Steffen Mitzner Hans-Peter Hartung Fritz Leutmezer Martin Sauer Uwe Zettl
Therapeutic options to treat multiple sclerosis (MS) relapses comprise glucocorticosteroids (GCS) as first-line and therapeutic plasma exchange (TPE) as second-line treatments in GCS-unresponsive patients. No guidelines exist for the treatment of another relapse following TPE. We retrospectively analyzed the responsiveness to GCS in a subsequent relapse following TPE in previously GCS-unresponsive MS patients. Thirty-seven patients with GCS-unresponsive MS relapses received TPE (relapse A). All patients developed another relapse after the completion of TPE and received GCS again (relapse B). The primary study endpoint was the clinical response to GCS and TPE. Marked improvement was defined as clinically significant improvement in function, moderate improvement as a definite change of symptoms without significant impact on function, no effect comprised unchanged symptoms, and deterioration a worsening of symptoms or new deficits. The secondary endpoint was an improvement in expanded disability status scale (EDSS) scoring. All patients were GCS-unresponsive during relapse A and received TPE. During GCS treatment of relapse B, marked improvement was observed in 10, moderate improvement in 24, and no effect in three patients. The EDSS decreased in 15 patients. GCS might remain the first-line relapse treatment following TPE in formerly GCS-unresponsive MS patients.
IJMS, Vol. 18, Pages 1746: Phellinus linteus Grown on Germinated Brown Rice Increases Cetuximab Sensitivity of KRAS-Mutated Colon Cancer
International Journal of Molecular Sciences doi: 10.3390/ijms18081746
Authors: Hye-Jin Park Jeong-Bin Park Sang-Jae Lee Minjung Song
Colon cancer is one of the most common types of cancer, and it has recently become a leading cause of death worldwide. Among colon cancers, the v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated form is notorious for its non-druggable features. Cetuximab, a monoclonal antibody that binds to the epidermal growth factor receptor, has been introduced as an antitumor therapy; however, secondary resistance and side effects significantly limit its effective use in these cancers. In this study, we prepared Phellinuslinteus on germinated brown rice (PBR) extracts to increase the sensitivity of KRAS-mutated colon cancers to cetuximab. The combined treatment of PBR extract and cetuximab suppressed SW480 cell viability/proliferation, with the cells exhibiting altered cellular morphology and clonogenic potential. AnnexinV–fluorescein isothiocyanate/propidium iodide–stained flow cytometry and Western blotting were performed, and PBR extract combined with cetuximab treatment increased apoptosis of the SW480 cells and suppressed their KRAS protein expression. The potential of PBR as a synergistic anticancer agent was further investigated in a tumor-xenografted mouse model. Tumor growth was significantly suppressed with PBR extract and cetuximab co-treatment. In conclusion, PBR increased the sensitivity of KRAS-mutated colon cancer cells to cetuximab, which indicates the potential use of PBR as a medical food against colon cancer.
This paper presents a new soil amendment used for immobilization of soil Pb, produced from vinegar residue, stainless steel slag, and weathered coal. The pH value measuring, granulation and adsorption experiments were carried out to determine the optimal composition of soil amendment. Optimizing soil amendment B2 was composed of vinegar residue, weathered coal (humic acid 61.53 wt%), and stainless steel slag with the ratio of 80∶16∶4, and particle size was in the range of 2–4 mm. In the leaching column experiment, B2 addition reduced the Pb release from the soil as well as increasing leachate pH and decreasing the bioavailable Pb concentration. The leachate Pb concentration decreased with lengthened leaching time under lower pH, but such a phenomenon disappeared in the rebounding period. Compared to control, the DTPA extractable Pb content in soil decreased by 12.41, 13.20, and 8.78% with the B2 addition amount of 1.00, 2.00, and 2.00 wt%, respectively. In addition, the total Pb content of each soil layer generally rose as B2 addition increased. It was concluded that application of B2 led to lower transport and transformation of Pb in soil. Based on the single chemical extraction, the environmental risk of Pb was decreased after application of B2. Meanwhile, soil amendment was also a new way to recycle vinegar residue, stainless steel slag, and weathered coal.
While research indicates that both the macro- and microstructure of sleep may be altered in fibromyalgia syndrome, few studies have controlled for symptom duration or included pain-control participants (i.e. patients with chronic pain and sleep disturbance not associated with fibromyalgia syndrome). A frequently reported alteration found in the sleep microstructure of patients with fibromyalgia syndrome is the alpha-delta sleep anomaly. Although alpha waves have been observed during N3 sleep in healthy individuals, it has been proposed that there is an increase in alpha wave activity during slow-wave sleep in fibromyalgia syndrome. Originally considered a possible neurological contribution to fibromyalgia syndrome, whether the alpha-delta sleep anomaly is fundamental to the development of fibromyalgia syndrome, or results mainly from the pain experience remains unknown. The present study was designed to compare sleep macro- and microstructure, and psychometric profiles, in three broadly age-matched groups of female participants: patients with fibromyalgia syndrome (n = 19); patients with osteoarthritis with sleep disturbance (n = 17); and healthy adults (n = 10). Patients with fibromyalgia syndrome met the American College of Rheumatology diagnostic criteria and were recruited within 6 months of diagnosis. Subjective sleep quality was significantly lowest, and levels of anxiety and depressive symptoms were significantly highest for patients with fibromyalgia syndrome. However, the groups showed no significant differences in polysomnographic measures of total sleep time, sleep latency and total wake after sleep onset. Levels of alpha-delta sleep were statistically similar in both clinical (fibromyalgia syndrome and osteoarthritis) groups, indicating that it is not a specific abnormality of fibromyalgia syndrome. Overall, subjective measurements of anxiety, depression, fatigue and sleep quality better discriminated between the three groups than did objective measurements of sleep variables.
Since there are no scientific data available about the role of spiritual care (SC) in Dutch ICUs, the goal of this quantitative study was twofold: first, to map the role of SC as a part of daily adult ICU care in The Netherlands from the perspective of intensivists, ICU nurses, and spiritual caregivers and second, to identify similarities and differences among these three perspectives. This study is the quantitative part of a mixed methods approach. To conduct empirical quantitative cohort research, separate digital questionnaires were sent to three different participant groups in Dutch ICUs, namely intensivists, ICU nurses, and spiritual caregivers working in academic and general hospitals and one specialist oncology hospital. Overall, 487 participants of 85 hospitals (99 intensivists, 290 ICU nurses, and 98 spiritual caregivers) responded. The majority of all respondents (>70%) considered the positive effects of SC provision to patients and relatives: contribution to mental well-being, processing and channeling of emotions, and increased patient and family satisfaction. The three disciplines diverged in their perceptions of how SC is currently evolving in terms of information, assessment, and provision. Nationwide, SC is not implemented in daily ICU care. The majority of respondents, however, attached great importance to interdisciplinary collaboration. In their view SC contributes positively to the well-being of patients and relatives in the ICU. Further qualitative research into how patients and relatives experience SC in the ICU is required in order to implement and standardize SC as a scientifically based integral part of daily ICU care.
Polycystic ovary syndrome (PCOS) is a complex disease, the etiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis, and insulin and glucose metabolism have been suggested as possible etiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyze the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro.
Serum samples were obtained from 288 female patients treated at the Center for Reproductive Medicine and Andrology (154 non-PCOS and 134 PCOS patients). DPP4 activity was measured by the conversion of the DPP4 substrate Gly-Pro p-nitroanilide hydrochloride and DPP4 concentration with a commercial ELISA. Luciferase reporter assays, qPCR and Western Blot analyses were performed for the in vitro evaluation of the activation of the DPP4 promoter by androgens.
DPP4 serum activity was increased in women with PCOS, regardless of which Rotterdam criteria led to the PCOS diagnosis. Furthermore, DPP4 serum levels were strongly correlated with the anti-Müllerian hormone (AMH) serum level. In vitro, the DPP4 promoter was stimulated by androgens in luciferase reporter assays, and DPP4 mRNA expression was increased in KGN granulosa carcinoma cells after androgen treatment.
The results suggested that a deregulation of DPP4 serum levels could be an additional characteristic of the metabolic imbalances associated with PCOS.
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IJERPH, Vol. 14, Pages 905: A Randomized Crossover Trial on Acute Stress-Related Physiological Responses to Mountain Hiking
International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14080905
Authors: Martin Niedermeier Carina Grafetstätter Arnulf Hartl Martin Kopp
Green exercise, defined as physical activity in natural environments, might have positive effects on stress-related physiological measures. Little is known about the acute effects of green exercise bouts lasting longer than 60 min. Therefore, the aim of the present study was to analyze the acute effects of a three-hour green exercise intervention (mountain hiking) on stress-related physiological responses. Using a randomized crossover design, 42 healthy participants were exposed to three different conditions in a field-based experiment: outdoor mountain hiking, indoor treadmill walking, and sedentary control condition (three hours each). At baseline and at follow-up (five minutes after the condition), stress-related physiological responses (salivary cortisol, blood pressure, and heart rate variability) were measured. Salivary cortisol decreased in all conditions, but showed a larger decrease after both mountain hiking and treadmill walking compared to the sedentary control situation (partial η2 = 0.10). No differences were found between mountain hiking and treadmill walking in salivary cortisol. In heart rate variability and blood pressure, changes from baseline to follow-up did not significantly differ between the three conditions. The results indicate that three hours of hiking indoors or outdoors elicits positive effects on salivary cortisol concentration. Environmental effects seem to play a minor role in salivary cortisol, blood pressure, and heart rate variability.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring alopecia with T-cell infiltration at the affected hair follicle.
Our aim was to study the potential link between hepatitis B virus (HBV) antigen exposure and AA.
Two pediatric patients with AA following hepatitis B vaccination were identified in a general dermatology clinic. A bioinformatics analysis and an electronic medical record (EMR) database query were performed at the University of Rochester Medical Center to identify patients with AA, coexisting viral infections, vaccinations, or interferon (IFN) therapy in order to determine if the presence of AA and these conditions was higher than in AA patients without these associated conditions or therapy.
An increased frequency of AA among those who received the HBV surface protein antigen [odds ratio (OR) 2.7, p < 0.0001] was identified, and an independent analysis revealed an increased frequency of AA in those receiving IFN-β treatment (OR 8.1, p < 0.05). One potential antigenic target identified was SLC45A2, a melanosomal transport protein important in skin and hair pigmentation. The longest potential vaccine peptide fragment match (8-mer) was to a segment of natural killer (NK) cell inhibitory receptors, KIR3DL2 and KIR3DL1. Predictive modeling of major histocompatibility complex (MHC)-peptide binding demonstrated potential binding of this peptide to MHC relevant to AA.
The results will need to be verified in additional patient databases allowing analysis of temporal relationships, and with molecular experiments of the identified antigens.
Our data confirm associations between viral infection and IFN treatment with AA. It establishes that the hepatitis B surface protein antigen has shared epitopes with human killer immunoglobulin-like receptors.
Der Massenanfall von Verletzten (MANV) stellt das Rettungssystem und die Kliniken vor große Herausforderungen. Aufgrund der zunehmenden Terroraktivitäten ist es erforderlich, sich mit dieser neuen Form der Bedrohung der Zivilgesellschaft im Hinblick auf die medizinische Versorgung der Terroropfer zu beschäftigen. Zwischen einem „normalen" MANV und einem TerrorMANV bestehen erhebliche Unterschiede im Hinblick auf die auftretenden Verletzungsmuster (stumpfes Trauma vs. penetrierendes/perforierendes Trauma), die Art und Weise des Geschehens (MANV = statische Lage vs. TerrorMANV = dynamische Lage) und die unterschiedlichen Sicherheitslagen (Rettungsdienstlage vs. Polizeilage). Dieser Artikel beschäftigt sich mit der Frage, welche Veränderungen diese neuen Anforderungen bei der chirurgischen Versorgung von Patienten erforderlich machen. Ärztliche Kollegen müssen sich mit den veränderten Verletzungsmustern vertraut machen, wobei hier die Schuss- und Explosionsverletzungen im Vordergrund stehen. Weiterhin sind geänderte taktisch-strategische Vorgehensweisen („damage controle surgery" vs. „tactical abbreviated surgical care") erforderlich, um möglichst vielen Patienten in einer Terrorlage das Überleben zu sichern und dabei gleichzeitig ein möglichst gutes funktionelles Ergebnis zu erreichen. Nur mit einer Änderung des „mindset" bei der Behandlung eines TerrorMANV gegenüber eines MANV wird es möglich sein, dieser neuen Herausforderung erfolgreich zu begegnen. Wesentliche Komponente dieses „mindset" ist, sich ein Maximum an Flexibilität anzueignen. Dazu möchte dieser Artikel beitragen.
Die Diagnose intraduktaler papillär-muzinöser Neoplasien (IPMN) des Pankreas hat mit der zunehmenden Verbreitung moderner abdomineller Bildgebungsverfahren in den letzten Jahren stark zugenommen. Trotz des malignen Potenzials werden insbesondere viele Seitengang-IPMN nicht sofort operiert, sondern überwacht. In den Fukuoka-Guidelines wurden im Jahr 2012 Risikofaktoren für eine potenziell maligne Transformation von Seitengang-IPMN zusammengefasst. Die Leitlinien definieren sog. „high-risk stigmata", bei deren Vorliegen eine Resektion durchgeführt werden sollte, sowie „worrisome features", bei welchen eine Überwachung zunächst empfohlen wird. Diese Therapierichtlinien werden jedoch kontrovers diskutiert, da auch viele Seitengang-IPMN, die „worrisome features" zeigen, ein relevantes malignes Potenzial aufweisen. Der vorliegende Artikel fasst die Indikation zur Operation und Möglichkeiten der chirurgischen Therapie von Seitengang-IPMN zusammen.
The human body hosts billions of microorganisms. According to one estimate, the ratio of bacterial cells to human cells is 10:1. There are an enormous diversity and specificity based on where the species live and how they interact with each other as well as the host. While bacterial species define how the host lives and adapts to its environment, host-associated factors also determine the microbiome and its components.
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| American Thyroid Association Awards Research Grant to Lawrence A. Shirley, MD, MS, FACS, Ohio State University ... Newswise (press release) Thyroid cancer currently has the highest increase rate and is projected to become by 2030 the fourth most common cancer among all patients and the second most common in women. Most patients are successfully treated with surgical excision and ... |
Sirtuin 7 (SIRT7), a member of the NAD+-dependent class III histone deacetylases, is involved in the regulation of various cellular processes and in resisting various stresses, such as hypoxia, low glucose levels, and DNA damage. Interestingly, SIRT7 is linked to the control of glycolysis, suggesting a role in glucose metabolism. Given the important roles of SIRT7, it is critical to clarify how SIRT7 activity is potentially regulated. It has been reported that some transcriptional and post-transcriptional regulatory mechanisms are involved. However, little is known how SIRT7 is regulated by the post-translational modifications. Here, we identified ubiquitin-specific peptidase 7 (USP7), a deubiquitinase, as a negative regulator of SIRT7. We showed that USP7 interacts with SIRT7 both in vitro and in vivo, and we further demonstrated that SIRT7 undergoes endogenous Lys-63-linked polyubiquitination, which is removed by USP7. Although the USP7-mediated deubiquitination of SIRT7 had no effect on its stability, the deubiquitination repressed its enzymatic activity. We also showed that USP7 coordinates with SIRT7 to regulate the expression of glucose-6-phosphatase catalytic subunit (G6PC), a gluconeogenic gene. USP7 depletion by RNA interference increased both G6PC expression and SIRT7 enzymatic activity. Moreover, SIRT7 targeted the G6PC promoter through the transcription factor ELK4 but not through forkhead box O1 (FoxO1). In summary, SIRT7 is a USP7 substrate and has a novel role as a regulator of gluconeogenesis. Our study may provide the basis for new clinical approaches to treat metabolic disorders related to glucose metabolism.
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Albumin is the most abundant plasma protein involved in the transport of many compounds, such as fatty acids, bilirubin, and heme. The endothelial cellular neonatal Fc receptor (FcRn) has been suggested to play a central role in maintaining high albumin plasma levels through a cellular recycling pathway. However, direct mapping of this process is still lacking. This work presents the use of wild-type and engineered recombinant albumins with either decreased or increased FcRn affinity in combination with a low or high FcRn-expressing endothelium cell line to clearly define the FcRn involvement, intracellular pathway, and kinetics of albumin trafficking by flow cytometry, quantitative confocal microscopy, and an albumin-recycling assay. We found that cellular albumin internalization was proportional to FcRn expression and albumin-binding affinity. Albumin accumulation in early endosomes was independent of FcRn-binding affinity, but differences in FcRn-binding affinities significantly affected the albumin distribution between late endosomes and lysosomes. Unlike albumin with low FcRn-binding affinity, albumin with high FcRn-binding affinity was directed less to the lysosomes, suggestive of FcRn-directed albumin salvage from lysosomal degradation. Furthermore, the amount of recycled albumin in cell culture media corresponded to FcRn-binding affinity, with a ∼3.3-fold increase after 1 h for the high FcRn-binding albumin variant compared with wild-type albumin. Together, these findings uncover an FcRn-dependent endosomal cellular-sorting pathway that has great importance in describing fundamental mechanisms of intracellular albumin recycling and the possibility to tune albumin-based therapeutic effects by FcRn-binding affinity.
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This is a response to a letter by Valadares and Woo (1).In an Addition and Correction, we tried to show that Mol A and B were captured in different reaction states. The two AMP molecules that were revealed by electron density in Mol B are in good shape and quite distinct from the molecule in Mol A described in our published paper (2). The flash-frozen crystal is a mixture of free Rv2837c, c-di-AMP–bound Rv2837c, pApA-bound Rv2837c, double-AMP–bound Rv2837c, single-AMP–bound Rv2837, even in transition states as well. It is understandable that those familiar with a perfect single crystal would have concern. The 5′-pApA was built as a nanoRNA of "AA." We appreciate what Drs. Valadares and Woo pointed out in their letter. Similar flaws do happen but rarely detour the understanding of the catalysis.As for the activity of Rv2837c on c-di-GMP, the data we have reported solidly support what has been observed from the structures. It is clear that Gentner's paper (3) supports rather than opposes our argument. Gentner et al. mentioned that c-di-GMP oligomerizes at high concentrations and becomes a monomer at physiological concentrations. Recently, Dey et al. (4) repeated the central part of the biochemistry in our paper and confirmed our result.At last, we agree with Valadares and Woo that more work is needed to clearly elucidate the hydrolytic process of 5′-pApA. Such elucidation of the kinetic process is far beyond the discussion of our paper since understanding the break and formation of chemical bonds needs the support of...
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Cry6Aa1 is a Bacillus thuringiensis (Bt) toxin active against nematodes and corn rootworm insects. Its 3D molecular structure, which has been recently elucidated, is unique among those known for other Bt toxins. Typical three-domain Bt toxins permeabilize receptor-free planar lipid bilayers (PLBs) by forming pores at doses in the 1–50 μg/ml range. Solubilization and proteolytic activation are necessary steps for PLB permeabilization. In contrast to other Bt toxins, Cry6Aa1 formed pores in receptor-free bilayers at doses as low as 200 pg/ml in a wide range of pH (5.5–9.5) and without the need of protease treatment. When Cry6Aa1 was preincubated with Western corn rootworm (WCRW) midgut juice or trypsin, 100 fg/ml of the toxin was sufficient to form pores in PLBs. The overall biophysical properties of the pores were similar for all three forms of the toxin (native, midgut juice- and trypsin-treated), with conductances ranging from 28 to 689 pS, except for their ionic selectivity, which was slightly cationic for the native and midgut juice-treated Cry6Aa1, whereas dual selectivity (to cations or anions) was observed for the pores formed by the trypsin-treated toxin. Enrichment of PLBs with WCRW midgut brush-border membrane material resulted in a 2000-fold reduction of the amount of native Cry6Aa1 required to form pores and affected the biophysical properties of both the native and trypsin-treated forms of the toxin. These results indicate that, although Cry6Aa1 forms pores, the molecular determinants of its mode of action are significantly different from those reported for other Bt toxins.
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Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1–20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris. We found that recombinant I62-CFH (protective against age-related macular degeneration) and V62-CFH functioned equivalently, matching or outperforming plasma-derived CFH, whereas R53H-CFH, linked to atypical hemolytic uremic syndrome (aHUS), was defective in C3bBb decay-accelerating activity (DAA) and factor I cofactor activity (CA). The aHUS-linked CCP 19 mutant D1119G-CFH had virtually no CA on (self-like) sheep erythrocytes (ES) but retained DAA. The aHUS-linked CCP 20 mutant S1191L/V1197A-CFH (LA-CFH) had dramatically reduced CA on ES but was less compromised in DAA. D1119G-CFH and LA-CFH both performed poorly at preventing complement-mediated hemolysis of ES. PspCN, a CFH-binding Streptococcus pneumoniae protein domain, binds CFH tightly and increases accessibility of CCPs 19 and 20. PspCN did not improve the DAA of any CFH variant on ES. Conversely, PspCN boosted the CA, on ES, of I62-CFH, R53H-CFH, and LA-CFH and also enhanced hemolysis protection by I62-CFH and LA-CFH. We conclude that CCPs 19 and 20 are critical for efficient CA on self-surfaces but less important for DAA. Exposing CCPs 19 and 20 with PspCN and thus enhancing CA on self-surfaces may reverse deficiencies of some CFH variants.
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Hydrogen sulfide (H2S) regulates various physiological processes, including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the trans-sulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response promoting a metabolic state primed for stress response. We show that H2S transiently increases phosphorylation of eukaryotic translation initiation factor 2 (eIF2α) resulting in inhibition of general protein synthesis. The H2S-induced increase in eIF2α phosphorylation was mediated at least in part by inhibition of protein phosphatase-1 (PP1c) via persulfidation at Cys-127. Overexpression of a PP1c cysteine mutant (C127S-PP1c) abrogated the H2S effect on eIF2α phosphorylation. Our data support a model in which H2S exerts its cytoprotective effect on ISR signaling by inducing a transient adaptive reprogramming of global mRNA translation. Although a transient increase in endogenous H2S production provides cytoprotection, its chronic increase such as in cystathionine β-synthase deficiency may pose a problem.
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Small GTPases are molecular switches that have critical biological roles and are controlled by GTPase-activating proteins and guanine nucleotide exchange factors (GEFs). The smg GDP dissociation stimulator (SmgGDS) protein functions as a GEF for the RhoA and RhoC small GTPases. SmgGDS has various regulatory roles, including small GTPase trafficking and localization and as a molecular chaperone, and interacts with many small GTPases possessing polybasic regions. Two SmgGDS splice variants, SmgGDS-558 and SmgGDS-607, differ in GEF activity and binding affinity for RhoA depending on the lipidation state, but the reasons for these differences are unclear. Here we determined the crystal structure of SmgGDS-558, revealing a fold containing tandem copies of armadillo repeats not present in other GEFs. We also observed that SmgGDS harbors distinct positively and negatively charged regions, both of which play critical roles in binding to RhoA and GEF activity. This is the first report demonstrating a relationship between the molecular function and atomic structure of SmgGDS. Our findings indicate that the two SmgGDS isoforms differ in GTPase binding and GEF activity, depending on the lipidation state, thus providing useful information about the cellular functions of SmgGDS in cells.
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In many Gram-negative bacteria, including Rhodobacter capsulatus, cytochrome c maturation (Ccm) is carried out by a membrane-integral machinery composed of nine proteins (CcmA to I). During this process, the periplasmic thiol-disulfide oxidoreductase DsbA is thought to catalyze the formation of a disulfide bond between the Cys residues at the apocytochrome c heme-binding site (CXXCH). Subsequently, a Ccm-specific thioreductive pathway involving CcmG and CcmH reduces this disulfide bond to allow covalent heme ligation. Currently, the sequence of thioredox reactions occurring between these components and apocytochrome c and the identity of their active Cys residues are unknown. In this work, we first investigated protein–protein interactions among the apocytochrome c, CcmG, and the heme-ligation components CcmF, CcmH, and CcmI. We found that they all interact with each other, forming a CcmFGHI–apocytochrome c complex. Using purified wild-type CcmG, CcmH, and apocytochrome c, as well as their respective Cys mutant variants, we determined the rates of thiol-disulfide exchange reactions between selected pairs of Cys residues from these proteins. We established that CcmG can efficiently reduce the disulfide bond of apocytochrome c and also resolve a mixed disulfide bond formed between apocytochrome c and CcmH. We further show that Cys-45 of CcmH and Cys-34 of apocytochrome c are most likely to form this mixed disulfide bond, which is consistent with the stereo-specificity of the heme–apocytochrome c ligation reaction. We conclude that CcmG confers efficiency, and CcmH ensures stereo-specificity during Ccm and present a comprehensive model for thioreduction reactions that lead to heme–apocytochrome c ligation.
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Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo-PRC2 from the fungus Chaetomium thermophilum captured in a bona fide autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously. We found that binding by the cofactor S-adenosylmethionine mitigates this autoinhibited structural state. Using steady-state enzyme kinetics, we also demonstrated that disrupting the autoinhibition results in a vastly activated enzyme complex. Autoinhibition provides a novel structural platform that may enable control of PRC2 activity in response to diverse transcriptional states and chromatin contexts and set a ground state to allow PRC2 activation by other cellular mechanisms as well.
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Cytochrome P450 (P450, CYP) 17A1 plays a critical role in steroid metabolism, catalyzing both the 17α-hydroxylation of pregnenolone and progesterone and the subsequent 17α,20-lyase reactions to form dehydroepiandrosterone (DHEA) and androstenedione (Andro), respectively, critical for generating glucocorticoids and androgens. Human P450 17A1 reaction rates examined are enhanced by the accessory protein cytochrome b5 (b5), but the exact role of b5 in P450 17A1-catalyzed reactions is unclear as are several details of these reactions. Here, we examined in detail the processivity of the 17α-hydroxylation and lyase steps. b5 did not enhance reaction rates by decreasing the koff rates of any of the steroids. Steroid binding to P450 17A1 was more complex than a simple two-state system. Pre-steady-state experiments indicated lag phases for Andro production from progesterone and for DHEA from pregnenolone, indicating a distributive character of the enzyme. However, we observed processivity in pregnenolone/DHEA pulse–chase experiments. (S)-Orteronel was three times more inhibitory toward the conversion of 17α-hydroxypregnenolone to DHEA than toward the 17α-hydroxylation of pregnenolone. IC50 values for (S)-orteronel were identical for blocking DHEA formation from pregnenolone and for 17α-hydroxylation, suggestive of processivity. Global kinetic modeling helped assign sets of rate constants for individual or groups of reactions, indicating that human P450 17A1 is an inherently distributive enzyme but that some processivity is present, i.e. some of the 17α-OH pregnenolone formed from pregnenolone did not dissociate from P450 17A1 before conversion to DHEA. Our results also suggest multiple conformations of P450 17A1, as previously proposed on the basis of NMR spectroscopy and X-ray crystallography.
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VOLUME 279 (2004) PAGES 35564–35572This article has been withdrawn by the authors after they discovered that Figs. 6 and 8 erroneously have panel duplications. A corrigendum cannot be issued by replacement with the correct panels as the original digital figures from prior to 2004 are no longer available. Although the overall conclusions of the study were validated by other approaches in the publication (i.e. Figs. 5, 7, and 9) and have since been confirmed by other investigators (e.g., Sanvicens, N., Gómez-Vicente, V., Masip, I., Messeguer, A., and Cotter, T. G. (2004) Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6. J. Biol. Chem. 279, 39268–39278 and Gómez-Vicente, V., Donovan, M., and Cotter, T. G. (2005) Multiple death pathways in retina-derived 661W cells following growth factor deprivation: Crosstalk between caspases and calpains. Cell Death Differ. 12, 796–804), the authors are voluntarily withdrawing the article to respect the highest standards of transparency and reliability of research.
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Recently, a single study revealed a new complex composed of Toll-like receptor 4 (TLR4), TLR6, and CD36 induced by fibrillary Aβ peptides, the hallmark of Alzheimer's disease. Unlike TLRs located on the plasma membrane that dimerize on the membrane after ligand binding to their extracellular domain, the TLR4-TLR6–CD36 complex assembly has been suggested to be induced by intracellular signals from CD36, similar to integrin inside-out signaling. However, the assembly site of TLR4-TLR6–CD36 and the domains participating in Aβ-induced signaling is still unknown. By interfering with TLR4-TLR6 dimerization using a TLR4-derived peptide, we show that receptor assembly is abrogated within the plasma membrane. Furthermore, we reveal that the transmembrane domains of TLR4 and TLR6 have an essential role in receptor dimerization and activation. Inhibition of TLR4-TLR6 assembly was associated with reduced secretion of proinflammatory mediators from microglia cells, ultimately rescuing neurons from death. Our findings support TLR4-TLR6 dimerization induced by Aβ. Moreover, we shed new light on TLR4-TLR6 assembly and localization and show the potential of inhibiting TLR4-TLR6 dimerization as a treatment of Alzheimer's disease.
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To find their DNA target sites in complex solution environments containing excess heterogeneous DNA, sequence-specific DNA-binding proteins execute various translocation mechanisms known collectively as facilitated diffusion. For proteins harboring a single DNA contact surface, long-range translocation occurs by jumping between widely spaced DNA segments. We have configured biosensor-based surface plasmon resonance to directly measure the affinity and kinetics of this intersegmental jumping by the ETS-family transcription factor ETS variant 6 (ETV6). To isolate intersegmental target binding in a functionally defined manner, we pre-equilibrated ETV6 with excess salmon sperm DNA, a heterogeneous polymer, before exposing the nonspecifically bound protein to immobilized oligomeric DNA harboring a high-affinity ETV6 site. In this way, the mechanism of ETV6–target association could be toggled electrostatically through varying NaCl concentration in the bulk solution. Direct measurements of association and dissociation kinetics of the site-specific complex indicated that 1) freely diffusive binding by ETV6 proceeds through a nonspecific-like intermediate, 2) intersegmental jumping is rate-limited by dissociation from the nonspecific polymer, and 3) dissociation of the specific complex is independent of the history of complex formation. These results show that target searches by proteins with an ETS domain, such as ETV6, whose single DNA-binding domain cannot contact both source and destination sites simultaneously, are nonetheless strongly modulated by intersegmental jumping in heterogeneous site environments. Our findings establish biosensors as a general technique for directly and specifically measuring target site search by DNA-binding proteins via intersegmental translocation.
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Apolipoprotein B mRNA-editing enzyme catalytic subunit 3 (APOBEC-3) enzymes are cytidine deaminases that are broadly and constitutively expressed. They are often up-regulated during carcinogenesis and candidate genes for causing the major single-base substitution in cancer-associated DNA mutations. Moreover, APOBEC-3s are involved in host innate immunity against many viruses. However, how APOBEC-3 mutational activity is regulated in normal and pathological conditions remains largely unknown. Heat shock protein levels are often elevated in both carcinogenesis and viral infection and are associated with DNA mutations. Here, using mutational analyses of hepatitis B virus (HBV), we found that Hsp90 stimulates deamination activity of APOBEC-3G (A3G), A3B, and A3C during co-expression in human liver HepG2 cells. Hsp90 directly stimulated A3G deamination activity when the purified proteins were used in in vitro reactions. Hsp40, -60, and -70 also had variable stimulatory effects in the cellular assay, but not in vitro. Sequencing analyses further demonstrated that Hsp90 increased both A3G cytosine mutation efficiency on HBV DNA and total HBV mutation frequency. In addition, Hsp90 shifted A3G's cytosine region selection in HBV DNA and increased A3G's 5′ nucleoside preference for deoxycytidine (5′-CC). Furthermore, the Hsp90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin dose dependently inhibited A3G and A3B mutational activity on HBV viral DNA. Hsp90 knockdown by siRNA or by Hsp90 active-site mutation also decreased A3G activity. These results indicate that heat shock proteins, in particular Hsp90, stimulate APOBEC-3–mediated DNA deamination activity, suggesting a potential physiological role in carcinogenesis and viral innate immunity.
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The endoplasmic reticulum (ER)–mitochondria encounter structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid exchange between the ER and mitochondria, protein import into mitochondria, and maintenance of mitochondrial morphology and genome. Here, we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of known ERMES roles in calcium regulation, phospholipid biosynthesis, or effects on mitochondrial morphology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels.
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Cell-to-cell transmission of intracellular protein aggregates is considered a central event in many neurodegenerative diseases, but little is known about the underlying molecular mechanisms. A new study employs fluorescence quenching to examine the fate of α-synuclein, a key molecule in the pathology of Parkinson's disease and related disorders, in primary cultured neurons, finding that endocytosis and lysosomal processing of exogenous fibrils may explain the transmission of α-synuclein pathology.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): A. Rachmiel, O. Emodi, D. Aizenbud, D. Rachmiel, D. Shilo
Distraction osteogenesis for the augmentation of severe alveolar bone deficiency has gained popularity during the past two decades. In cases where the vertical bone height is not sufficient to create a stable transport segment, performing alveolar distraction osteogenesis (ADO) is not possible. In these severe cases, a two-stage treatment protocol is suggested: onlay bone grafting followed by ADO. An iliac crest onlay bone graft followed by ADO was performed in 13 patients: seven in the mandible and six in the maxilla. Following ADO, endosseous implants and prosthetic restorations were placed. In all cases, the onlay bone graft resulted in inadequate height for implant placement, but allowed ADO to be performed. ADO was performed to a mean total vertical augmentation of 13.7mm. Fifty-two endosseous implants were placed. During a mean follow-up of 4.85 years, two implants failed, both during the first 6 months; the survival rate was 96.15%. In severe cases lacking the required bone for ADO, using an onlay bone graft as a first stage treatment increases the bone height thus allowing ADO to be performed. This article describes a safe and stable two-stage treatment modality for severely atrophic cases, resulting in sufficient bone for implant placement and correction of the inter-maxillary vertical relationship.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M.A. Pogrel, S.L. Ruggiero
This article reports a type of localized osteonecrosis that can occur in patients who have had successful osseointegrated implants for many years and then commence anti-resorptive therapy. Eleven female patients were identified who had successful implant insertion, but who were placed on anti-resorptive therapy (bisphosphonates or denosumab) several years later and developed osteonecrosis around the implants. In each case, the osteonecrosis occurred only around the implants and not around the patient's remaining teeth. The implants of eight patients were removed with a sequestrum of bone tightly adherent to the implant. This is different from the normal pattern of implant failure. Implant failure can occur when patients with successfully integrated implants are later placed on anti-resorptive therapy, and the osteonecrosis takes a particular form where a sequestrum forms that remains adherent to the implant. Why the adjacent remaining teeth are not affected is unclear.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): L. Huang, X. Gao, T. Su, C.-H. Jiang, X.-C. Jian
This study evaluated the effects of three different incision designs for the vertical platysma myocutaneous flap (VPMF): apron, MacFee, and T-shaped. This flap was used for the reconstruction of intraoral defects following cancer ablation in selected patients. Sixty-eight cases of VPMF reconstruction were assessed: the apron incision was used in 28, MacFee incision in 22, and T-shaped incision in 18. With regard to postoperative outcomes, there were 26 cases of flap survival and two of partial necrosis with the apron incision; 20 of survival and two of partial necrosis with the MacFee incision; 15 of survival and three of partial necrosis with the T-shaped incision. Success rates were 92.9%, 90.9% and 83.3%, respectively, for VPMF with the apron, MacFee, and T-shaped incisions. A wound healing disturbance in the neck was seen in three cases of VPMF with the apron incision and one case with the MacFee incision. The MacFee incision had the best aesthetic effect, and the postoperative neck scar was more obvious for the T-shaped incision. It is recommended that VPMF with the MacFee or apron incision be used for the reconstruction of larger buccal mucosa and floor of the mouth defects, while VPMF with the T-shaped incision should be used for smaller intraoral defects, especially tongue defects of the lateral surface.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R.M. Uhrich, M. Sherban, C. Valdez
While sharp, penetrating trauma is often associated with group A Streptococcus (GAS) infections and subsequent necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS), there are scant reports in the oral and maxillofacial surgery literature regarding blunt, non-penetrating trauma in association with these conditions. With a clinical course that initially appears relatively benign following blunt trauma, NF can progress swiftly through the fascial planes and may quickly become life-threatening if the oral and maxillofacial surgeon fails to recognize some of the critical pathognomonic signs. The case of a 64-year-old female who suffered a ground-level mechanical fall with a minimally displaced lateral orbital wall fracture is reported here. This seemingly benign, non-penetrating injury subsequently developed into rapidly progressive, fatal NF and STSS. This case is used to highlight the necessity for early detection of NF and STSS prior to rapid clinical decline, as these scenarios, particularly bilateral peri-orbital NF with resulting mortality, have been reported infrequently following blunt, craniofacial trauma in the literature related to this specialty.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): A. Rachmiel, O. Emodi, D. Aizenbud, D. Rachmiel, D. Shilo
Distraction osteogenesis for the augmentation of severe alveolar bone deficiency has gained popularity during the past two decades. In cases where the vertical bone height is not sufficient to create a stable transport segment, performing alveolar distraction osteogenesis (ADO) is not possible. In these severe cases, a two-stage treatment protocol is suggested: onlay bone grafting followed by ADO. An iliac crest onlay bone graft followed by ADO was performed in 13 patients: seven in the mandible and six in the maxilla. Following ADO, endosseous implants and prosthetic restorations were placed. In all cases, the onlay bone graft resulted in inadequate height for implant placement, but allowed ADO to be performed. ADO was performed to a mean total vertical augmentation of 13.7mm. Fifty-two endosseous implants were placed. During a mean follow-up of 4.85 years, two implants failed, both during the first 6 months; the survival rate was 96.15%. In severe cases lacking the required bone for ADO, using an onlay bone graft as a first stage treatment increases the bone height thus allowing ADO to be performed. This article describes a safe and stable two-stage treatment modality for severely atrophic cases, resulting in sufficient bone for implant placement and correction of the inter-maxillary vertical relationship.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M.A. Pogrel, S.L. Ruggiero
This article reports a type of localized osteonecrosis that can occur in patients who have had successful osseointegrated implants for many years and then commence anti-resorptive therapy. Eleven female patients were identified who had successful implant insertion, but who were placed on anti-resorptive therapy (bisphosphonates or denosumab) several years later and developed osteonecrosis around the implants. In each case, the osteonecrosis occurred only around the implants and not around the patient's remaining teeth. The implants of eight patients were removed with a sequestrum of bone tightly adherent to the implant. This is different from the normal pattern of implant failure. Implant failure can occur when patients with successfully integrated implants are later placed on anti-resorptive therapy, and the osteonecrosis takes a particular form where a sequestrum forms that remains adherent to the implant. Why the adjacent remaining teeth are not affected is unclear.
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Publication date: Available online 10 August 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): L. Huang, X. Gao, T. Su, C.-H. Jiang, X.-C. Jian
This study evaluated the effects of three different incision designs for the vertical platysma myocutaneous flap (VPMF): apron, MacFee, and T-shaped. This flap was used for the reconstruction of intraoral defects following cancer ablation in selected patients. Sixty-eight cases of VPMF reconstruction were assessed: the apron incision was used in 28, MacFee incision in 22, and T-shaped incision in 18. With regard to postoperative outcomes, there were 26 cases of flap survival and two of partial necrosis with the apron incision; 20 of survival and two of partial necrosis with the MacFee incision; 15 of survival and three of partial necrosis with the T-shaped incision. Success rates were 92.9%, 90.9% and 83.3%, respectively, for VPMF with the apron, MacFee, and T-shaped incisions. A wound healing disturbance in the neck was seen in three cases of VPMF with the apron incision and one case with the MacFee incision. The MacFee incision had the best aesthetic effect, and the postoperative neck scar was more obvious for the T-shaped incision. It is recommended that VPMF with the MacFee or apron incision be used for the reconstruction of larger buccal mucosa and floor of the mouth defects, while VPMF with the T-shaped incision should be used for smaller intraoral defects, especially tongue defects of the lateral surface.
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| News-Medical.net | Types of Blood Cancer News-Medical.net The production and function of blood cells are affected by blood cancer. Blood is produced in the bone marrow, where most of these cancers originate. Three types of blood cells that mature and develop from the stem cells of bone marrow are red blood ... |
Publication date: Available online 10 August 2017
Source:Cryobiology
Author(s): Md Mahbubul Hassan, Xiaoxu Li, Jian G. Qin
Low survival of cryopreserved sperm impedes the application of cryopreservation technique in spermcasting oyster species. This study developed a simple method of liquid nitrogen vapor freezing to improve post-thaw sperm survival in the spermcasting oyster Ostrea angasi. The results indicate that the permeable cryoprotectants, dimethyl sulfoxide (DMSO), ethylene glycol (EG) and propylene glycol (PG) were non-toxic to sperm up to 20% concentration and 90 min exposure whereas methanol at 10% or higher was toxic to sperm for any exposure over 30 min. Among the treatments with permeable cryoprotectants, 15% EG produced the highest post-thaw sperm motility. Sperm motility was further improved by the addition of non-permeable cryoprotectants (trehalose and glucose), with 15% EG + 0.2 M trehalose resulting in the highest post-thaw sperm motility among all the combinations evaluated. The durations of 20, 30 and 60 min equilibrations produced a higher post-thaw sperm motility and plasma membrane integrity (PMI) than 10 min. Higher post-thaw motility and PMI were achieved by freezing sperm at the 8 cm height from the liquid nitrogen surface than at the 2, 4, 6, 10 or 12 cm height. Holding sperm for 10 min in liquid nitrogen vapor produced higher post-thaw motility and PMI than for 2, 5 or 20 min. The cryopreservation protocol developed in this study improved both post-thaw motility and PMI of O. angasi sperm at least 15% higher than those cryopreserved using programmable freezing method. Liquid nitrogen vapor freezing might have greater applicability in improving post-thaw sperm quality of spermcasting oyster species.
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Publication date: Available online 10 August 2017
Source:Cryobiology
Author(s): P.C. dos Santos-Neto, F. Cuadro, N. Barrera, M. Crispo, A. Menchaca
The objective was to evaluate pregnancy outcomes and birth rate of in vivo derived vs. in vitro produced ovine embryos submitted to different cryopreservation methods. A total of 197 in vivo and 240 in vitro produced embryos were cryopreserved either by conventional freezing, or by vitrification with Cryotop or Spatula MVD methods on Day 6 after insemination/fertilization. After thawing/warming and transfer, embryo survival rate on Day 30 of gestation was affected by the source of the embryos (in vivo 53.3%, in vitro 20.8%; P < 0.05) and by the method of cryopreservation (conventional freezing 26.5%, Cryotop 52.0%, Spatula MVD 22.2%; P < 0.05). For in vivo derived embryos, survival rate after embryo transfer was 45.6% for conventional freezing, 67.1% for Cryotop, and 40.4% for Spatula MVD. For in vitro produced embryos, survival rate was 7.3% for conventional freezing, 38.7% for Cryotop, and 11.4% for Spatula MVD. Fetal loss from Day 30 to birth showed a tendency to be greater for in vitro (15.0%) rather than for in vivo produced embryos (5.7%), and was not affected by the cryopreservation method. Gestation length, weight at birth and lamb survival rate after birth were not affected by the source of the embryo, the cryopreservation method or stage of development (average: 150.5 ± 1.8 days; 4232.8 ± 102.8 g; 85.4%; respectively). This study demonstrates that embryo survival and birth rate of both in vivo and in vitro produced ovine embryos are improved by vitrification with the minimum volume Cryotop method.
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BACKGROUND: Prehospital trauma triage ensures proper transport of patients at risk of severe injury to hospitals with an appropriate corresponding level of trauma care. Incorrect triage results in undertriage and overtriage. The American College of Surgeons Committee on Trauma recommends an undertriage rate below 5% and an overtriage rate below 50% for prehospital trauma triage protocols. To find the most accurate prehospital trauma triage protocol, a clear overview of all currently available protocols and corresponding outcomes is necessary. OBJECTIVES: The aim of this systematic review was to evaluate the current literature on all available prehospital trauma triage protocols and determine accuracy of protocol-based triage quality in terms of sensitivity and specificity. METHODS: A search of Pubmed, Embase, and Cochrane Library databases was performed to identify all studies describing prehospital trauma triage protocols before November 2016. The search terms included "trauma," "trauma center," or "trauma system" combined with "triage," "undertriage," or "overtriage." All studies describing protocol-based triage quality were reviewed. To assess the quality of these type of studies, a new critical appraisal tool was developed. RESULTS: In this review, 21 articles were included with numbers of patients ranging from 130 to over 1 million. Significant predictors for severe injury were: vital signs, suspicion of certain anatomic injuries, mechanism of injury, and age. Sensitivity ranged from 10% to 100%; specificity from 9% to 100%. Nearly all protocols had a low sensitivity, thereby failing to identify severely injured patients. Additionally, the critical appraisal showed poor quality of the majority of included studies. CONCLUSION: This systematic review shows that nearly all protocols are incapable of identifying severely injured patients. Future studies of high methodological quality should be performed to improve prehospital trauma triage protocols. LEVEL OF EVIDENCE: Systematic review, level III.| Thyroid Cancer - Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2017 Markets Insider LONDON, Aug. 10, 2017 /PRNewswire/ -- DelveInsight's, Thyroid Cancer - Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2017" report provides comprehensive insights about marketed and Phase III products for the Thyroid Cancer. and more » |
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Tomohiro Noguchi, Chizuru Utsugi, Makoto Kashiwayanagi
(Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors. Release of GABA from inhibitory interneurons at the olfactory bulb induces inhibitory currents at the mitral cells, which are output neurons from the olfactory bulb. (Design) In the present study, we measured spontaneous inhibitory postsynaptic currents (sIPSCs) at the mitral cells of mice fed a soft diet in order to explore the effects of changes in texture of diets on neural function at the olfactory bulb. (Results) The soft-diet feeding extended the intervals between sIPSCs and reduced their peak amplitudes. (Conclusions) The present results suggest that soft-diet feeding in mice attenuates the neural functions of inhibitory interneurons at the olfactory bulb.
| Protecting Kids Against HPV Before Cancer Risk Increases Newswise (press release) However, the medical data clearly indicates that the HPV vaccine is extremely safe and highly effective at preventing cancers of the cervix, vagina, and vulva in women and cancers of the penis and anus in men; and oropharynx (tonsils) cancer in both sexes. |
Chronic traumatic encephalopathy (CTE): a degenerative disease of the brain (form of brain damage) that occurs in athletes or others who have experienced repetitive concussions or other trauma to the brain. Some of the most common symptoms and signs of CTE can include memory loss, behavioral difficulties like difficulty with impulse control, impaired judgment, aggression, balance problems, a slow onset of dementia, and depression. Symptoms of CTE might be mistaken for symptoms due to the aging process or other conditions like Alzheimer's disease.
Publication date: July 2017
Source:Bioactive Carbohydrates and Dietary Fibre, Volume 11
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In this interview we discuss the issue of burnout in oncology, including signs and risk factors, how it might affect patient care, and strategies for prevention. (Source: CancerNetwork)
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This video reviews the role of surgery in patients with stage III (N2) non –small-cell lung cancer, highlighting some of the challenges in studying these patients and the need for multidisciplinary patient evaluations. (Source: CancerNetwork)
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Germline mutations in pancreatic cancer susceptibility genes were commonly identified in a group of patients with pancreatic cancer who did not report a significant family history of cancer, according to the results of a single-center study. (Source: CancerNetwork)
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Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.
In this study, we investigated the cytotoxic activity of the hypoxia-activated prodrug evofosfamide against human osteosarcoma cells in vitro as a single agent and in combination with proapoptotic receptor agonist's dulanermin and drozitumab. We then assessed the anticancer activity of evofosfamide alone and in combination with drozitumab using a clinically relevant orthotopic mouse model of osteosarcoma and on subsequent pulmonary metastases. Evofosfamide as a single agent reduced tumor burden in bone and cooperated with drozitumab to protect bone from osteosarcoma-induced bone destruction while also reducing the incidence of pulmonary metastases and importantly, evofosfamide alone and in combination with drozitumab was not toxic to normal bone metabolism in vivo.
| Vaccinating children against HPV could prevent cancer risk in later life News-Medical.net However, the medical data clearly indicates that the HPV vaccine is extremely safe and highly effective at preventing cancers of the cervix, vagina, and vulva in women and cancers of the penis and anus in men; and oropharynx (tonsils) cancer in both sexes. and more » |
| A Hard Road | Couple's Net | Chandrama Anderson | Almanac Online | The Almanac Online (blog) I want to share an excerpt from another new book of mine: A Hard Road It's a story of cancer survival for patients and caregivers.We hope it will help you as you ... and more » |
