Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia

Abstract

Objectives

We investigated the effects of deep brain stimulation (DBS) or lesions of the ventral intermediate nucleus (Vim) of the thalamus for spinocerebellar ataxia (SCA) and examined the pathophysiological role of neuronal activity of the Vim underlying ataxia.

Methods

Five patients with SCA with cortical atrophy (ages 60-69 years; 2 sporadic and three familial SCA) and five patients with essential tremor (ET) (ages 57–71 years) were treated with Vim surgery. Intraoperatively, we recorded neuronal activity from single neurons in the Vim thalamus while patients were at rest and compared the physiological properties of those neurons between patients with SCA and those with ET.

Results

Postsurgery mean scores for the Fahn–Tolosa–Marin Tremor Scale were improved from 78 to 44 in SCA patients and from 54 to 21 in ET patients. Stronger stimulation was necessary to optimize outcomes in SCA as compared to ET patients. We analyzed 68 Vim neurons in SCA and 60 Vim neurons in ET. Mean discharge rates, burst characteristics, and oscillatory activity were similar for both patient groups, however, we observed that the ratio of cells responding to passive manipulation was significantly smaller (P = 0.0001) in SCA (22%) than in ET (71%).

Interpretation

Thalamic surgery led to a significant improvement in tremor in SCA patients. One potential mechanism underlying ataxia in SCA may be disruption of cerebellar sensory feedback, which modulates motor commands in the cerebello-thalamo-cortical network.

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Mise en ligne du N° 6, volume 62 (décembre 2017) de la revue 'Annales de chirurgie plastique esthétique'

Vol 62 - N°6 - décembre 2017 P. 601-678 © 2017, Elsevier Masson SAS

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Zinc Detoxification: A Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells

Cells require some metals, such as zinc and manganese, but excess levels of these metals can be toxic. As a result, cells have evolved complex mechanisms for maintaining metal homeostasis and surviving metal intoxication. Here, we present the results of a large-scale functional genomic screen in Drosophila cultured cells for modifiers of zinc chloride toxicity, together with transcriptomics data for wildtype or genetically zinc-sensitized cells challenged with mild zinc chloride supplementation. Altogether, we identified 47 genes for which knockdown conferred sensitivity or resistance to toxic zinc or manganese chloride treatment, and more than 1800 putative zinc-responsive genes. Analysis of the 'omics data points to the relevance of ion transporters, glutathione-related factors, and conserved disease-associated genes in zinc detoxification. Specific genes identified in the zinc screen include orthologs of human disease-associated genes CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that knockdown of red dog mine (rdog; CG11897), a candidate zinc detoxification gene encoding an ABCC-type transporter family protein related to yeast cadmium factor (YCF1), confers sensitivity to zinc intoxication in cultured cells and that rdog is transcriptionally up-regulated in response to zinc stress. As there are many links between the biology of zinc and other metals and human health, the 'omics datasets presented here provide a resource that will allow researchers to explore metal biology in the context of diverse health-relevant processes.

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PRC2 is Dispensable in Vivo for {beta}-Catenin-Mediated Repression of Chondrogenesis in Mouse Embryonic Cranial Mesenchyme

A hallmark of craniofacial development is the differentiation of multiple cell lineages in close proximity to one another. The mouse skull bones and overlying dermis are derived from the cranial mesenchyme (CM). Cell fate selection of the embryonic cranial bone and dermis in the CM requires Wnt/β-catenin signaling, and loss of β-catenin leads to an ectopic chondrogenic cell fate switch. The mechanism by which Wnt/β-catenin activity suppresses the cartilage fate is unclear. Upon conditional deletion of β-catenin in the CM, several key determinants of the cartilage differentiation program, including Sox9, become differentially expressed. Many of these differentially expressed genes are known targets of the Polycomb Repressive Complex 2 (PRC2). Thus, we hypothesized that PRC2 is required for Wnt/β-catenin-mediated repression of chondrogenesis in the embryonic CM. We find that β-catenin can physically interact with PRC2 components in the CM in vivo. However, upon genetic deletion of Enhancer of Zeste homolog 2 (EZH2), the catalytic component of PRC2, chondrogenesis remains repressed and the bone and dermis cell fate is preserved in the CM. Furthermore, loss of β-catenin does not alter either the H3K27me3 enrichment levels genome-wide or on cartilage differentiation determinants, including Sox9. Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/β-catenin signaling.

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Growth of Caenorhabditis elegans in Defined Media Is Dependent on Presence of Particulate Matter

Caenorhabditis elegans are typically cultured in a monoxenic medium consisting of live bacteria. However, this introduces a secondary organism to experiments and restricts the manipulation of the nutritional environment. Due to the intricate link between genes and environment, greater control and understanding of nutritional factors are required to push the C. elegans field into new areas. For decades, attempts to develop a chemically defined, axenic medium as an alternative for culturing C. elegans have been made. However, the mechanism by which the filter feeder C. elegans obtain nutrients from these liquid media is not known. Using a fluorescence-activated cell sorting based approach, we demonstrate growth in all past axenic C. elegans media to be dependent on the presence of previously unknown particles. This particle requirement of C. elegans led to development of liposome-based, nanoparticle culturing that allows full control of nutrients delivered to C. elegans.

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Homelessness and Emergency Medicine: A Review of the Literature

Abstract

Objectives

We aimed to synthesize the available evidence on the demographics, prevalence, and clinical characteristics, and evidence-based management of homeless persons in the Emergency Department (ED). Where appropriate, we highlight knowledge gaps and suggest directions for future research.

Methods

We conducted a systematic literature search following databases: PubMed, Ovid, and Google Scholar for articles published between January 1, 1990 and December 31, 2016. We supplemented this search by cross-referencing bibliographies of the retrieved publications. Peer-reviewed studies written in English and conducted in the United States (US) that examined homelessness within the ED setting were included. We used a qualitative approach to synthesize the existing literature.

Results

Twenty-eight studies were identified that met the inclusion criteria. Based on our study objectives and the available literature, we grouped articles examining homeless populations in the ED into four broad categories: 1) Prevalence and socio-demographic characteristics of homeless ED visits; 2) ED utilization by homeless adults; 3) Clinical characteristics of homeless ED visits; 4) Medical education and evidence-based management of homeless ED patients.

Conclusion

Homelessness may be under-recognized in the ED setting. Homeless ED patients have distinct care needs and patterns of ED utilization that are unmet by the current disease-oriented and episodic models of emergency medicine. More research is needed to determine the prevalence and characteristics of homelessness in the ED and to develop evidence-based treatment strategies in caring for this vulnerable population.

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Ameliorative Effect of Cactus (Opuntia ficus indica) Extract on Lithium-Induced Nephrocardiotoxicity: A Biochemical and Histopathological Study

Opuntia ficus indica (family Cactaceae) is used in the treatment of a variety of conditions including metal-induced toxicity. The study reports the protective effects of Opuntia ficus indica (CCE) against lithium carbonate-induced toxicity in rats. Nephrocardiotoxicity was induced in male Wistar rats by single dose of lithium carbonate (25 mg/kg b.w twice daily for 30 days). Aqueous extract of Opuntia ficus indica was administered at the dose of 100 mg/kg of b.w by gavage for 60 days. Obtained results revealed that administration of lithium carbonate caused a significant increase in serum creatinine, uric acid, and urea levels. Additionally, a significant decrease in the level of renal and cardiac SOD, CAT, and GPx activities was associated with a significant increase of MDA levels in lithium carbonate group more than those of the control. However, the treatment of experimental rats with CCE prevented these alterations and maintained the antioxidant status. The histopathological observations supported the biochemical evidences of nephrocardioprotection. CCE supplementation could protect against lithium carbonate-induced renal and cardiac injuries in rats, plausibly by the upregulation of antioxidant enzymes and inhibition of MDA to confer the protective effect.

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Triclocarban and Triclosan Inhibit Human Aromatase via Different Mechanisms

Human aromatase (CYP19A1) is an important enzyme, which produces estrogen from androgen for maintaining the female reproductive function and pregnancy. Triclocarban and triclosan are antimicrobial chemicals added to personal care, household, and industrial products. They could be endocrine disruptors and may disrupt human CYP19A1 activity. In the present study, we investigated the effects of triclocarban and triclosan on estradiol production and human CYP19A1 activity in JEG-3 cells. Triclocarban and triclosan reduced estradiol production in JEG-3 cells. Triclocarban and triclosan inhibited human CYP19A1 with IC50 values of 15.81 and 6.26 μM, respectively. Triclosan competitively inhibited CYP19A1, while triclocarban noncompetitively inhibited this enzyme. Docking study showed that triclosan bound to the steroid-binding pocket of CYP19A1, while triclocarban was off this target, suggesting a different mechanism. In conclusion, triclocarban and triclosan are inhibitors of human CYP19A1.

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“Tulip bundle rescue” troubleshooting over-the-scope clip (OTSC) failure in ERCP-related duodenal perforation (Stapfer I)

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Conventional versus traction-assisted endoscopic submucosal dissection for gastric neoplasms: a multicenter, randomized controlled trial (with video)

To clarify whether dental floss clip traction improves the technical outcomes of endoscopic submucosal dissection (ESD).

http://ift.tt/2jgOVOO

Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable to an age- and gender-matched control population: case-control study with expert pathology review

Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) due to microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients to a matched control population.

http://ift.tt/2B6MhSK

Time latencies of Helicobacter pylori eradication after peptic ulcer and risk of recurrent ulcer, ulcer adverse events, and gastric cancer: a population-based cohort study

Helicobacter pylori (H pylori) is associated with peptic ulcer disease and gastric cancer.

http://ift.tt/2jjc3vU

Safety and efficacy of lumen-apposing metal stents with and without simultaneous double-pigtail plastic stents for draining pancreatic

Lumen-apposing metal stents (LAMSs) are used to perform necrosectomy in walled-off necrosis (WON). Although necrosectomy is not required for pancreatic pseudocyst (PP), an increasing number of PPs are also being drained with LAMSs in view of their ease of deployment. The aim of the present study was to evaluate the safety and efficacy of using LAMSs to drain PPs.

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An ascariasis revealed by videocapsule endoscopy

Abstract

A 68-year-old woman, native from Madagascar, was referred to the Gastroenterology unit investigating an episode of melena in April 2015. She has a history of systemic sclerosis and Gougerot-Sjogren syndrome diagnosed in 2014 without systemic treatment. Her laboratory tests just showed anemia (10 g/dL), without eosinophilia nor other abnormality.She is living in metropolitan France since 1988, but returned annually to Madagascar.

This article is protected by copyright. All rights reserved.

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A Facile Protocol to Generate Site-Specifically Acetylated Proteins in Escherichia Coli

Genetic code expansion serves as a powerful tool to study a wide range of biological processes, including protein acetylation. Here we demonstrate a facile protocol to exploit this technique for generating homogeneously acetylated proteins at specific sites in Escherichia coli cells.

http://ift.tt/2jCvFrP

Enchondromatosis-associated oligodendroglioma: case report and literature review

Abstract

Enchondromatosis is a rare skeletal disorder characterized by the development of multiple enchondromas, which can also manifest non-cartilage tumors including gliomas. Here, we describe a genetic analysis of a low-grade glioma that developed in an enchondromatosis case. A 32-year-old man with a long history of enchondromatosis developed a left frontal tumor. The histopathological findings of his surgical specimen revealed characteristics of a low-grade glioma with an IDH1 c.395G>A (R132H) mutation and 1p/19q codeletion, which led to a definitive diagnosis of oligodendroglioma. A common point mutation in IDH1 (R132H) was detected in the patient's enchondroma and glioma-matched pair specimens. To the best of our knowledge, this is the first case of molecularly confirmed oligodendroglioma associated with enchondromatosis. Furthermore, identification of a common IDH1 mutation in enchondroma and oligodendroglioma-matched pair specimens supports the hypothesis that IDH1/2 mosaicism initiates tumorigenesis.

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Streamlined 3D Cerebellar Differentiation Protocol with Optional 2D Modification

We describe a simplified 3D differentiation protocol for hPSCs, using defined medium and reduced growth factors, capable of generating cell aggregates with early neuroepithelial structures and positive for cerebellar-associated markers, as well as an optional 2D modification for differentiating cells as a monolayer to generate functional neurons.

http://ift.tt/2iHYZwa

Current and Future Therapeutic Regimens for Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH)

Abstract

NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced stage of fibrosis, it is not an independent predictor of long term mortality. In contrast, there is significant data to suggest that stage of fibrosis is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, a number of important secondary endpoints, including non-invasive biomarkers, long term outcomes, and patient reported outcomes, must be considered. In 2017, a few phase 3 clinical trials for treatment of NASH are in progress. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH enriches the pipeline of emerging therapies. Conclusion: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. This article is protected by copyright. All rights reserved.

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A Cure for Hemophilia within Reach

Severe hemophilia has changed from a debilitating disease to a condition that is compatible with normal life, provided that patients receive a diagnosis early and also receive prophylactic therapy. The disease burden is now related largely to the demanding infusions and the development of…

http://ift.tt/2Bn0ED1

AAV5–Factor VIII Gene Transfer in Severe Hemophilia A

Hemophilia A, an X-linked bleeding disorder, results from mutations in the gene encoding coagulation factor VIII. Patients with severe hemophilia A (factor VIII activity level, Although many patients with hemophilia A receive exogenous factor VIII only when bleeding occurs (on-demand therapy), the…

http://ift.tt/2AOXRBd

A Cure for Hemophilia within Reach

Severe hemophilia has changed from a debilitating disease to a condition that is compatible with normal life, provided that patients receive a diagnosis early and also receive prophylactic therapy. The disease burden is now related largely to the demanding infusions and the development of…

http://ift.tt/2Bn0ED1

AAV5–Factor VIII Gene Transfer in Severe Hemophilia A

Hemophilia A, an X-linked bleeding disorder, results from mutations in the gene encoding coagulation factor VIII. Patients with severe hemophilia A (factor VIII activity level, Although many patients with hemophilia A receive exogenous factor VIII only when bleeding occurs (on-demand therapy), the…

http://ift.tt/2AOXRBd

Pyroptosis, a Novel Player for Alcoholic Hepatitis?

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Diagnostic Modalities for Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH) and Associated Fibrosis

Abstract

NAFLD is a spectrum comprised of isolated steatosis, NASH, advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and don't carry a significant risk for adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high prevalence rates to low rates are noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition as an important liver disease, the diagnosis of NASH still requires a liver biopsy which is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, it suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathologic features. A number of non-invasive modalities to diagnose NASH and stage liver fibrosis are being developed. These include predictive models (NAFLD fibrosis score) and serum biomarkers such as Enhanced Liver Fibrosis, (ELF). Other tests are based on radiologic techniques such as transient or MR elastography (MRE) which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have AUROC between 0.76 to 0.90% with MRE having the best predictive performance. In summary, developing accurate, safe and easily accessible non-invasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease but to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. This article is protected by copyright. All rights reserved.

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Evolving role of Obeticholic acid in primary biliary cholangitis

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Ectopic expansion of engineered human liver tissue seeds using mature cell populations

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NAFLD, Metabolic Syndrome, and the Fight That Will Define Clinical Practice for a Generation of Hepatologists

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Transplanting HCV-positive livers into HCV-negative patients with preemptive antiviral treatment: A modeling study

ABSTRACT

Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: 1) willing to accept any (HCV-negative or HCV-positive) liver versus 2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when MELD was ≥ 20, and the benefit was highest at MELD 28 (0.172 additional life years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, i.e. Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust.

Conclusions: Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. This article is protected by copyright. All rights reserved.

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Regression of HCV cirrhosis: Time will tell

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Fibrolamellar Carcinoma in the Carney Complex: PRKAR1A Loss Instead of the Classic DNAJB1-PRKACA Fusion

Abstract

Fibrolamellar carcinomas are characterized by activation of protein kinase A, a kinase composed of catalytic and regulatory subunits. PRKACA encodes a catalytic subunit of protein kinase A and almost all fibrolamellar carcinomas have a heterozygous 400kb deletion that leads to the fusion of DNAJB1 and PRKACA. The resulting DNAJB1-PRKACA fusion transcript is believed to activate protein kinase A by dysregulation of the catalytic portion of the protein. In contrast, PRKAR1A encodes one of the regulatory subunits of protein kinase A. We hypothesized that loss of function of this regulatory unit could also lead to protein kinase A activation and thus to fibrolamellar carcinoma. Since PRKAR1A mutations underlie the Carney complex, we searched for liver tumors in individuals with the Carney complex.

We identified 3 individuals with fibrolamellar carcinomas and a personal history of the Carney complex. All 3 tumors displayed the typical morphology of fibrolamellar carcinoma and were positive for Arginase, CK7 and CD68. FISH was negative for PRKACA rearrangements. However, PRKAR1A sequencing identified pathogenic mutations in two of two cases with successful sequencing. In addition, all 3 cases were negative for PRKAR1A protein expression, consistent with inactivation of this key regulatory unit of Protein kinase A. We also identified one additional fibrolamellar carcinoma in an individual without a documented history of the Carney Complex that was negative for PRKACA rearrangements but had loss of PRKAR1A protein expression as well as PRKAR1A mutations.

In conclusion, fibrolamellar carcinoma can be part of the Carney complex. In this setting, fibrolamellar carcinomas have inactivating PRKAR1A mutations instead of the DNAJB1-PRKACA fusion gene found in sporadic fibrolamellar carcinomas, providing an alternate means for activation of protein kinase A. This article is protected by copyright. All rights reserved.

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Road to Recovery: Road Drawings in a Gender-Specific Residential Substance Use Treatment Center

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Supervisee Art-Based Disclosure in El Duende Process Painting

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Interview With Myra Levick

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Remembering Ron Hays

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The First Decade of Biosemiotics

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Denitrifying haloarchaea: sources and sinks of nitrogenous gases

Abstract

Haloarchaea thrive under saline and hypersaline conditions and often dominate microbial communities in saltmarshes, salted lakes/soils, and some oceanic areas. Some of the predominant species show denitrifying capabilities, although it remains unclear whether they are complete or partial denitrifiers. As complete denitrifiers, they could play important roles buffering ecosystems in which nitrate and nitrite appear as contaminants. However, partial denitrifying haloarchaea could contribute to the emission of nitrogenous gasses, thus acting as drivers of climate change and ozone depletion. In this review, we summarise some recent results on denitrification in haloarchaea, discuss the environmental implications and outline possible applications in mitigation. Finally, we list questions to be addressed in the near future, facilitating increased understanding of the role of these organisms in N turnover in arid and hypersaline environments.

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How obstetricians and pregnant women decide mode of birth in light of a recent regulation in Brazil

Publication date: Available online 8 December 2017
Source:Women and Birth
Author(s): Rachel Galvao, Nicola L. Hawley, Carolina Silveira da Silva, Mariângela F. Silveira
BackgroundIn Brazil, 88% of births among women with private insurance are caesarean sections, even though a caesarean rate above 15% is associated with greater maternal and child morbidity and mortality. Aiming to reduce unnecessary caesarean sections in the private sector, in July 2015 the Brazilian government enacted Resolução Normativa 368, a regulation requiring the use of partograms, pre-natal cards to document pregnancies, and consent forms for elective caesareans, and recommending that obstetricians provide women with an informational letter about birth.AimsThis study aimed to describe Brazilian women's experiences deciding their mode of birth and obstetricians' roles in this decision-making process after Resolução Normativa 368's enactment.MethodsInterviews were conducted with obstetricians (n=8) and women who had recently given birth (n=19) in Pelotas, Brazil, and the constant comparative method was used to identify emergent themes.FindingsResolução Normativa 368's provisions do not appear to affect decision-making about birth mode. Reportedly, consent forms were rarely used, and were viewed as bureaucratic formalities. Obstetricians described consistent use of pre-natal cards and partograms, but all participants were unaware of informational letters about birth. Moreover, women viewed caesarean sections as a way to avoid pain, and obstetricians felt that vaginal birth's long duration, unpredictability, and low remuneration contribute to high caesarean section rates.ConclusionsImproved enforcement of Resolução Normativa 368, accompanied by structural changes like an on-call schedule and higher compensation for vaginal births in the private sector, could better inform patients about modes of birth and incentivise physicians to encourage vaginal birth.



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Identifying and monitoring neurons that undergo metamorphosis-regulated cell death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in Drosophila melanogaster

Abstract

Activation of caspases is an essential step toward initiating apoptotic cell death. During metamorphosis of Drosophila melanogaster, many larval neurons are programmed for elimination to establish an adult central nervous system (CNS) as well as peripheral nervous system (PNS). However, their neuronal functions have remained mostly unknown due to the lack of proper tools to identify them. To obtain detailed information about the neurochemical phenotypes of the doomed larval neurons and their timing of death, we generated a new GFP-based caspase sensor (Casor) that is designed to change its subcellular position from the cell membrane to the nucleus following proteolytic cleavage by active caspases. Ectopic expression of Casor in vCrz and bursicon, two different peptidergic neuronal groups that had been well-characterized for their metamorphic programmed cell death, showed clear nuclear translocation of Casor in a caspase-dependent manner before their death. We found similar events in some cholinergic neurons from both CNS and PNS. Moreover, Casor also reported significant caspase activities in the ventral and dorsal common excitatory larval motoneurons shortly after puparium formation. These motoneurons were previously unknown for their apoptotic fate. Unlike the events seen in the neurons, expression of Casor in non-neuronal cell types, such as glial cells and S2 cells, resulted in the formation of cytoplasmic aggregates, preventing its use as a caspase sensor in these cell types. Nonetheless, our results support Casor as a valuable molecular tool not only for identifying novel groups of neurons that become caspase-active during metamorphosis but also for monitoring developmental timing and cytological changes within the dying neurons.

http://ift.tt/2B4R7zR

Social cognition and aggression in methamphetamine dependence with and without a history of psychosis

Abstract

In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p < .001). Additionally, performance decrements were significantly greater in MAP (p = .040), compared to MA-dependent participants. While deficits in recognising emotional expressions were restricted to anger in the MA group (p = .020), a generalized impairment across all four emotions was observed in MAP (all p ≤ .001). Additionally, both patient groups demonstrated higher levels of aggression than CTRLs, yet no association was found with social cognition. This study supported the notion of deficits in recognising facial emotional expressions and inferring mental states of others in MA dependence, with additional impairments in MAP. Failure to detect an association between social cognitive impairment and aggressive behaviour may implicate independent disturbances of the two phenomena in MA dependence.

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Cost-Effectiveness of Treatments for the Management of Bone Metastases: A Systematic Literature Review

Abstract

Background

Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective.

Objective

The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases.

Methods

We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines.

Results

Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment.

Conclusions

The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive.

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Expanding the use of abiraterone in prostate cancer: Is earlier always better?

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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer

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The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib

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http://ift.tt/2kICDiB

Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics

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http://ift.tt/2iGWVol

Image-guided adaptive radiotherapy improves acute toxicity during intensity-modulated radiation therapy for head and neck cancer

Abstract

Purpose

The purpose of this study was to evaluate the impact of an image-guided adaptive re-planning strategy on patients treated by intensity-modulated radiotherapy (IMRT) for head and neck cancer.

Methods and materials

Among 198 patients with head and neck cancer comprising the primary study population, 79 (40%) underwent adaptive radiotherapy with modification of the original IMRT midway during treatment.

Results

The incidence of grade 3+ acute skin toxicity was 15 and 35% among patients treated with and without adaptive radiotherapy, respectively (p = 0.01). The incidence of grade 3+ oral mucositis was 15 and 29%, respectively (p = 0.03). There was no significant difference in the 2-year rates of local-regional control or overall survival between the two cohorts (p > 0.05, for both).

Conclusion

The use of an image-guided adaptive radiotherapy strategy reduced the incidence of high-grade skin toxicity and oral mucositis in the acute setting. Further studies are needed to better define which subset of patients may benefit the most.

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Clinical laboratory verification of thyroglobulin concentrations in the presence of autoantibodies to thyroglobulin: comparison of EIA, radioimmunoassay and LC MS/MS measurements in an Urban Hospital

Thyroglobulin (Tg) measurements assess recurrence in post-thyroidectomy thyroid cancer patients. Tg measurements by enzyme immunoassays (EIA) can be falsely elevated by interference from Tg autoantibodies (TgA...

http://ift.tt/2B4gSAs

Factors associated with the achievement of cervical smears by general practitioners

Reliable data about general practitioners performing pap-tests are insufficient. A claim code for the achievement of pap-smears exists in France, but its use by general practitioners is not known. The main pur...

http://ift.tt/2jgpEnJ

Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces NETosis and prevents septic shock-induced coagulopathy in rats

Septic shock-induced disseminated intravascular coagulation is responsible for increased occurrence of multiple organ dysfunction and mortality. Immunothrombosis-induced coagulopathy may contribute to hypercoa...

http://ift.tt/2AEV7nT

Associations between CRYBA4 gene variants and high myopia in a Japanese population

http://ift.tt/2yRhLtX

Erratum

Martina Minnerop, Delia Kurzwelly, Holger Wagner, Anne S. Soehn, Jennifer Reichbauer, Feifei Tao, et al. Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. Brain 2017; 140: 1561–1578, http://ift.tt/2kJbo7j.

http://ift.tt/2iFGcSq

Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey

Abstract

Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

http://ift.tt/2BmYPFR

Percutaneous Image-Guided Cryoneurolysis

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2ALTcjr

Changing Utilization of Noninvasive Diagnostic Imaging Over 2 Decades: An Examination Family–Focused Analysis of Medicare Claims Using the Neiman Imaging Types of Service Categorization System

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2AM1WpO

Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2BmzCvy

Making Time for Patients: Positive Impact of Direct Patient Reporting

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2AMkfLC

Evaluation of antioxidant, anti-inflammatory, analgesic and antipyretic activities of the stem bark of Sapindus mukorossi

Saponins are the main constituents of genus Sapindus and have the therapeutic potential for inflammatory disorders. In this study the antioxidant, anti-inflammatory, analgesic and antipyretic potential of the ste...

http://ift.tt/2je6gYI