No abstract available
http://ift.tt/2ySNsS8
Παρασκευή 27 Οκτωβρίου 2017
5. Epilepsy and EEG activity in early-onset Alzheimer’s disease
The aim of this review was to evaluate and summarize the current literature regarding the incidence and features of epileptic seizures in early onset Alzheimer's disease (AD) as well as its epileptiform characteristics as described by electroencephalography (EEG).
http://ift.tt/2y9wwtj
2. Do repeated limbic seizures induce depression-like behavior in rats?
It has been reported that rapid kindling of the hippocampus produces lasting depression-like behavior in rats, as evidenced by increased immobility in the forced swim test and a loss of preference for sweetened water (Mazarati et al., 2007). This might suggest that repeated limbic seizure activity could be the cause of the depression often seen in patients with temporal lobe epilepsy.Sixty-day old male Wistar rats were implanted with electrodes in the amygdala and ventral hippocampus and kindled (or sham kindled) daily to a criterion of 10 stage 5 seizures.
http://ift.tt/2y9MlAt
1. Across all the seven seas: Fifty years in neurology, EEG and epilepsies
Since the 1960s, major neuroscience advances have facilitated the development of new antiepilepsy drugs (AEDs) targeting specific neurotransmitter-receptor systems, particularly the GABAergic, the NMDA-receptors and voltage-gated ion channels. In addition to the classical AEDs, carbamazepine and cogeners act at the voltage-gates sodium channels, while ethosuxumide acts at the calcium channel, improving the treatment of partial and generalized seizures. But approximately 30% of partial complex seizures remain refractory to AEDs, leading to novel AEDs: levetiracetam, tiagabine, lacosamide, perampanel and others.
http://ift.tt/2ln2CvN
Ultrasound in polyneuropathies – Is size or structure all that matters?
Polyneuropathies (PNPs) are systemic disorders of the peripheral nervous system, that may variably affect motor, sensory and autonomic nerve fibers. The etiological classification of PNPs still remains a challenging aspect of ongoing research, especially taking into account, that the early identification and therapy of immune-mediated causes may improve the functional outcome of the patient (Viala et al., 2010; Joint Task Force of the EFNS and the PNS, 2010). The continuous need for objective, morphological description of pathological peripheral nerve conditions led over the time to the development of different ultrasound measures and protocols, capable of quantifying and scoring the examiner's observations (Kerasnoudis et al., 2014a, 2016; Grimm et al., 2016; Padua et al., 2012).
http://ift.tt/2yaBGp9
Machine-Based Classification of ADHD and nonADHD Participants Using Time/Frequency Features of Event-Related Neuroelectric Activity
Biological signals are a challenge to analyse. Among these signals, the electrophysiological activity of the human brain during cognitive processing is undoubtedly the most challenging. For decades, neuroscientists have been studying the brain-mind relationship based on the electrophysiological responses of the brain. Most studies have been performed on signals in the time domain in the form of event-related potentials (ERPs). The starting point of a second approach was based on the principle that complex signals are composed of oscillatory responses of different frequencies (for a review, see Başar, 2011; Karakaş and Barry, 2017; Karakaş and Başar, 2004).
http://ift.tt/2lnsIPk
Feasibility of Deep Brain Stimulation for Controlling the Lower Urinary Tract Functions: An Animal Study
Lower urinary tract (LUT) dysfunction is an increasingly common symptom worldwide. Neurological disorders are one of the main causes of LUT dysfunction. Specifically, aging-induced central neurodegeneration affects neurological control of bladder function. Since complex networks of the autonomic nervous system and central nervous system control micturition reflexes (Gomez-Pinilla et al., 2007), central neuromodulations are a potential approach for treating various troublesome of LUT disorders (Ju and Liao, 2016).
http://ift.tt/2y952nL
Intraoperative direct cortical stimulation motor evoked potentials: Stimulus parameter recommendations based on rheobase and chronaxie
One elicits intraoperative direct cortical stimulation (DCS) muscle motor evoked potentials (MEPs) with a short train of monophasic rectangular electrical pulses having a user-selected interstimulus interval (ISI) and pulse duration (D). While practitioners commonly choose 4ms ISI and 0.5msD, reported parameters vary and none have been proven optimal, leaving no consistent scientific rationale for the selection (Taniguchi et al., 1993; Cedzich et al., 1996; Kombos et al., 2000; Neuloh et al., 2004; Kombos et al., 2009; Kamada et al., 2009; Szelényi et al., 2010; Nossek et al., 2011).
http://ift.tt/2ybbavX
Plasticity induced by non-invasive transcranial brain stimulation: A position paper
Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are the most commonly used methods of non-invasive transcranial brain stimulation that has been abbreviated by previous authors as either as NIBS or NTBS. Here we use NIBS since it seems to be the most common term at the present time. When it was first introduced in 1985, TMS was employed primarily as a tool to investigate the integrity and function of the human corticospinal system (Barker et al., 1985). Single pulse stimulation was used to elicit motor evoked potentials (MEPs) that were easily evoked and measured in contralateral muscles (Rothwell et al., 1999).
http://ift.tt/2log3LV
Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects
Transcranial Magnetic Stimulation (TMS) is a versatile tool for studying human neurophysiology in vivo (Barker et al., 1985; Hallett, 2007; Rossini and Rossi, 2007). Single TMS pulses applied to the primary motor cortex (M1) can elicit motor evoked potentials (MEPs) in contralateral muscles that can be quantified using surface electromyography (EMG). The amplitude of MEPs averaged across batches of single pulses provides an index of cortico-motor reactivity (Rothwell, 1997). When applied in repetitive trains (repetitive TMS, rTMS) or in specific patterns inspired by synaptic plasticity protocols (theta-burst stimulation, TBS), TMS can produce changes in cortico-motor excitability, indexed by changes in MEP amplitude.
http://ift.tt/2ybatme
Termination patterns of stimulus-induced rhythmic, periodic, or ictal patterns and spontaneous electrographic seizures
Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are rhythmic, periodic, or ictal-appearing patterns consistently elicited by stimulation of the patient (i.e. suctioning, physical examination of the patient, noxious stimulation, or sudden ambient noise) (Hirsch et al., 2004). They are a relatively common finding in the critically ill, with reported prevalence of 10–34% (Braksick et al., 2016; Hirsch et al., 2004; Ong et al., 2012). The reported causes of SIRPIDs include intracerebral hemorrhage, traumatic brain injury, anoxic brain injury, metabolic disturbances, and drug toxicity amongst other etiologies (Braksick et al., 2016).
http://ift.tt/2lkA7ip
Spinal segmental myoclonus resembling “belly dance” in a pregnant woman
Myoclonus is a movement disorder with a wide differential diagnosis (Shibasaki, 2006) but with common semiological elements: sudden, brief, jerky movements, caused by muscle contraction or inhibition of ongoing muscle activity. Myoclonus can be classified by presumed site of origin into cortical, cortical-subcortical, subcortical-supraspinal, spinal and peripheral (Shibasaki, 2006). Neurophysiologic studies help confirm clinical diagnosis and understand underlying physiological mechanisms.
http://ift.tt/2y9wwcN
Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations
Throughout childhood and adolescence, healthy brain development is characterized by a range of neurobiological changes, such as synaptic pruning and myelination of long-distance axons (Craik and Bialystok, 2006) that ultimately lead to a matured brain that enables fast signal transduction while maintaining relatively low energy costs (Boersma et al., 2011). The organization of normal adult brain networks is described as an intermediate structure between tree extremes: (1) a locally connected, highly ordered (regular) network, (2) a random network and (3) a scale-free network, which is characterized by highly connected brain areas, or 'hubs' (Stam, 2014).
http://ift.tt/2lqRjD5
Corticomuscular coherence in the acute and subacute phase after stroke
Stroke results from critically reduced blood flow to the brain tissue due to bleeding or obstruction of arteries. Globally, stroke remains a major cause of disability despite advances in preventive treatment and in acute management (Hankey, 2017). The most common impairment caused by stroke is motor disability affecting approximately 80% of the patients, most frequently seen as hemiparesis (Langhorne et al., 2009). Spontaneous recovery may occur in the following weeks and months after stroke and can be facilitated through rehabilitation involving exercise (Maulden et al., 2005).
http://ift.tt/2y9J1W6
Fasciculations in nerve and muscle disorders – A prospective study of muscle ultrasound compared to electromyography
Fasciculations can be encountered in patients presenting with symptoms of nerve and muscle disorders (NMD) and can also be found in healthy subjects (HS). Fasciculations associated with chronic changes are clinically important findings in diagnosing amyotrophic lateral sclerosis (ALS) (Reimers et al., 1996; de Carvalho et al., 2008; Brooks, 1994; Costa et al., 2012; Mills, 2010) and were recognised as a part of the diagnostic criteria known as the Awaji criteria (de Carvalho et al., 2008). Electromyography (EMG) describes fasciculations as brief, involuntary muscle activity that represents the spontaneous discharge of a motor unit or a part hereof (Reimers et al., 1996) and it has been used to describe the complexity and the firing frequency of fasciculations in different disorders (Mills, 2010).
http://ift.tt/2lmpXxD
Dual mTOR Kinases MLN0128 Inhibitor Sensitizes HR+/HER2+ Breast Cancer Patient-derived Xenografts to Trastuzumab or Fulvestrant
Purpose: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized. Experimental Design: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis. Results: Estrogen acted as a growth-driver of trastuzumab-resistant COH-SC31 tumors, but an accelerator in trastuzumab-sensitive COH-SC1 model. In vivo trastuzumab efficacy examination further confirmed the consistent responses between PDXs and the corresponding tumors. Integrative omics analysis revealed that mammalian target of rapamycin (mTOR) and ERα signaling predominantly regulate tumor growth of the two HR+/HER2+ PDXs. Combination of dual mTOR complex inhibitor MLN0128 and anti-HER2 trastuzumab strongly suppressed tumor growth of COH-SC1 PDX accompanied with increasing ER-positive cell population in vivo. Instead, MLN0128 in combination with anti-estrogen fulvestrant significantly halted the growth of HR+/HER2+ cancer cells in vitro and trastuzumab-resistant COH-SC31 as well as trastuzumab-sensitive COH-SC1 tumors in vivo. Conclusion:Compared to the standard trastuzumab treatment, this study demonstrates alternative therapeutic strategies against HR+/HER2+ tumors through establishment of two PDXs coupling with integrative omics analyses and in vivo drug efficacy examination. This work presents a prototype of future "co-clinical" trials to tailor personalized medicine in clinical practice.
http://ift.tt/2yYf8qO
Phosphorylation of Pnut at the Early Steps of Drosophila Embryo Development Affects Association of the Septin Complex with Membrane and Is Important for Viability
Septin proteins are polymerizing GTPases that are found in most eukaryotic species. Septins are important for cytokinesis and participate in many processes involving spatial modifications of the cell cortex. In Drosophila, septin proteins Pnut, Sep1 and Sep2 form a hexameric septin complex. Here, we found that septin protein Pnut is phosphorylated during the first two hours of Drosophila embryo development. To study the effect of Pnut phosphorylation in a live organism, we created a new Drosophila pnut null mutant which allows for the analysis of Pnut mutations during embryogenesis. To understand the functional significance of Pnut phosphorylation, Drosophila strains carrying non-phosphorylatable and phospho-mimetic mutant pnut transgenes were established. The expression of the non-phosphorylatable Pnut protein resulted in semi-lethality and abnormal protein localization, whereas, the expression of the phospho-mimetic mutant form of Pnut disrupted the assembly of a functional septin complex and septin filament formation in vitro. Overall, our findings indicate that the controlled phosphorylation of Pnut plays an important role in regulating septin complex functions during organism development.
http://ift.tt/2zWzr6c
Non-canonical GA and GG 5' Intron Donor Splice Sites Are Common in the Copepod Eurytemora affinis
The non-canonical 5' intron donor splice sites GA and GG are exceedingly rare in described eukaryotic genomes, however they are present in approximately 12% of introns in the genome of the copepod Eurytemora affinis. Failure to recognize the high frequency of these donor sites compromised the modeling of genes in this newly sequenced genome, including ten conserved ionotropic glutamate receptor family genes curated herein. These introns appear to have been acquired recently, along with many additional idiosyncratic introns. Their high frequency implies the evolution of modified intron donor splice site recognition in this copepod.
http://ift.tt/2xup8oe
ARSDA: A New Approach for Storing, Transmitting and Analyzing Transcriptomic Data
Two major stumbling blocks exist in high-throughput sequencing (HTS) data analysis. The first is the sheer file size typically in gigabytes when uncompressed, causing problems in storage, transmission and analysis. However, these files do not need to be so large and can be reduced without loss of information. Each HTS file, either in compressed .SRA or plain text .fastq format, contains numerous identical reads stored as separate entries. For example, among 44603541 forward reads in the SRR4011234.sra file (from a Bacillus subtilis transcriptomic study) deposited at NCBI's SRA database, one read has 497027 identical copies. Instead of storing them as separate entries, one can and should store them as a single entry with the SeqID_NumCopy format (which I dub as FASTA+ format). The second is the proper allocation of reads that map equally well to paralogous genes. I illustrate in detail a new method for such allocation. I have developed ARSDA software that implement these new approaches. A number of HTS files for model species are in the process of being processed and deposited at http://ift.tt/2mcG65G to demonstrate that this approach not only saves a huge amount of storage space and transmission bandwidth, but also dramatically reduces time in downstream data analysis. Instead of matching the 497027 identical reads separately against the Bacillus subtilis genome, one only needs to match it once. ARSDA includes functions to take advantage of HTS data in the new sequence format for downstream data analysis such as gene expression characterization. I contrasted gene expression results between ARSDA and Cufflinks so readers can better appreciate the strength of ARSDA. ARSDA is freely available for Windows, Linux and Macintosh computers at http://ift.tt/2mcMbPE.
http://ift.tt/2zWzkri
Understanding microRNA Regulation Involved in the Metamorphosis of the Veined Rapa Whelk (Rapana venosa)
The veined rapa whelk (Rapana venosa) is widely consumed in China. Nevertheless, it preys on oceanic bivalves, thereby reducing this resource worldwide. Its larval metamorphosis comprises transition from pelagic to benthic form, which implicates considerable physiological and structural changes and plays vital roles in its natural populations and commercial breeding. Thus, understanding the endogenous microRNAs that drive metamorphosis is of great interest. This is the first study to use high-throughput sequencing to examine the alterations in microRNA (miRNA) expression that occur during metamorphosis in a marine gastropod. A total of 195 differentially expressed miRNAs was obtained. Sixty-five of these were expressed during the transition from pre-competent- to competent larvae. Thirty-three of these were upregulated and the others were downregulated. Another 123 miRNAs were expressed during the transition from competent- to post-larvae. Ninety-six of these were upregulated and the remaining 27 were downregulated. The expression of miR-276-y, miR-100-x, miR-183-x, and miR-263-x showed an over 100-fold change during development, while the miR-242-x and novel-m0052-3p expression levels changed over 3000-fold. Putative target gene co-expression, gene ontology, and pathway analyses suggest that these miRNAs play important roles in cell proliferation, migration, apoptosis, metabolic regulation, and energy absorption. Twenty miRNAs and their target genes involved in ingestion, digestion, cytoskeleton, cell adhesion, and apoptosis were identified. Nine of them were analysed with real-time PCR, which showed an inverse correlation between the miRNA and their relative expression levels. Our data elucidates the role of microRNAs in R. venosa metamorphic transition and serve as a solid basis for further investigation into regulatory mechanism of gastropod metamorphosis.
http://ift.tt/2xup0Fg
RNA-Based Genetic Circuits Are a Potential Antitumor Immunotherapy [Research Watch]
Expression of synthetic RNA-based gene circuits in tumors induces an antitumor T-cell response.
http://ift.tt/2gIWZD6
Trastuzumab Deruxtecan Is Safe and Active in HER2-Expressing Tumors [Research Watch]
Trastuzumab deruxtecan achieved responses in patients with breast, gastric, and gastroesophageal tumors.
http://ift.tt/2ialZDE
Adrenergic Nerves May Promote Angiogenesis in Prostate Cancer [Research Watch]
Deleting Adrb2, encoding the β2-adrenergic receptor, in tumor endothelial cells suppresses angiogenesis.
http://ift.tt/2gIWSaE
Identified Selective USP7 Inhibitors Compete with Ubiquitin Binding [Research Watch]
Specific USP7 inhibitors stabilized p53 and exhibited toxicity in tumor cells in vitro and in vivo.
http://ift.tt/2i95OpS
Cancer "Clock" Opens New Therapeutic Avenues [News in Brief]
A better understanding of circadian genes, the focus of the 2017 Medicine Nobel, could improve patient care.
http://ift.tt/2gHPjAS
SLC38A9 Links mTORC1 Activity to Lysosomal Amino Acid Release [Research Watch]
SLC38A9 acts as a lysosomal arginine sensor to activate mTORC1 signaling and support tumor growth.
http://ift.tt/2iaqT3f
C1 neurons: a nodal point for stress?
Abstract
The C1 cells are catecholaminergic and glutamatergic neurons located in the rostral ventrolateral medulla (RVLM). Collectively, these neurons innervate sympathetic and parasympathetic preganglionic neurons, the hypothalamic paraventricular nucleus, and countless brain structures involved in autonomic regulation, arousal and stress. Optogenetic inhibition of rostral C1 neurons has little effect on BP at rest in conscious rats but produces large BP drops when the animals are anesthetized or exposed to hypoxia. Optogenetic C1 stimulation increases BP and produces arousal from non-REM sleep. C1 cell stimulation mimics the effect of restraint stress to attenuate kidney injury caused by renal ischemia-reperfusion. These effects are mediated by the sympathetic nervous system through the spleen and eliminated by silencing the C1 neurons. These few examples illustrate that, depending on the nature of the stress, the C1 cells mediate adaptive responses of a homeostatic or allostatic nature.
This article is protected by copyright. All rights reserved
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Virtual Presurgical Planning Optimizes the Outcome for a Patient with Ameloblastoma
By the time 31-year-old Marcus King saw Ron Karni, MD, and Kunal Jain, MD, the ameloblastoma encompassed the majority of... Read the full article...http://ift.tt/2yaXLnm
Dr. Amber Luong Recognized for Clinical Excellence by UTHealth’s Women Faculty Forum
Amber Luong, MD, PhD, associate professor of otorhinolaryngology and research director for the department, has been recognized with the 2017... Read the full article...http://ift.tt/2yatchR
Dr. William Yao Selected Faculty Member of the Year by ORL Residents
Each year, the faculty of the Department of Otorhinolaryngology-Head and Neck Surgery at McGovern Medical School at UTHealth recognizes an... Read the full article...http://ift.tt/2yb2XYp
Dr. Soham Roy, Dr. William Yao and Dr. Ibrahim Alava Receive Dean’s Teaching Excellence Awards
Soham Roy, MD, FACS, FAAP, Ibrahim "Trey" Alava, MD, and William Yao, MD, have been recognized with McGovern Medical School... Read the full article...http://ift.tt/2yat3uP
Factors Associated with Response to Biofeedback Therapy for Dyssynergic Defecation
Biofeedback therapy (BT) is effective for dyssynergic defecation (DD), but it is not widely available or reimbursed, and is labor intensive. It is therefore important to select the appropriate patients for this treatment. We investigated symptoms and demographic, manometric, and other factors associated with outcomes of BT in patients with DD.
http://ift.tt/2xtG9iq
Sub acute rehabilitation does have benefits for patients with advanced cancer
It is with concern we read a recent Letter to the Editor (Desai et al., 50(2), 2017) that stated 'people with gastrointestinal cancer did not benefit from the admission to sub-acute rehabilitation', concluding that inpatient rehabilitation could do more harm than good. People with advanced cancer may not always achieve physical gains following rehabilitation but to state there is no benefit is an over-simplification. This was a very small sample size (n=22), one third of whom had metastatic pancreas cancer where rapid functional decline is seen in the last weeks of life.
http://ift.tt/2yaD1w2
Managing Peripheral Facial Palsy
Physicians frequently encounter patients with acute-onset peripheral facial palsy in the emergency department (ED). Although many cases are idiopathic (eg, Bell's palsy), others are associated with identifiable causes. Regardless of the cause, 85% of patients recover some function, with more than 70% achieving complete recovery.1 The most appropriate treatment depends on the cause, which is often unknown at the ED evaluation. We discuss our approach to patients with peripheral facial palsy according to available evidence and, when the evidence is less clear, our expertise in this area (Figure 1 and Table 1).
http://ift.tt/2zKtWXi
Human subthalamic oscillatory dynamics following somatosensory stimulation
The functional significance of neural oscillations in somatosensory and motor control has been of growing interest in the last years. Specific frequency changes can be elicited both during voluntary (Pfurtscheller and Aranibar, 1977; Salenius et al., 1997) and passive movements (Alegre et al., 2002; Cassim et al., 2001), as well as due to somatosensory stimulation (Hari and Forss, 1999). Besides focusing on sensorimotor mu and beta rhythms the investigation of gamma and high-frequency (> 100 Hz) oscillations has gained increasing interest.
http://ift.tt/2yRULJV
Reply to “Stimulus, response and excitability – what is new?”
We thank Burke and Kiernan for their interesting and constructive comments (Burke and Kiernan, 2017) on our recent Letter to the Editor (Milants et al., 2017). We agree with most of these comments. It is absolutely correct that by considering only iMAX, we lose valuable information related to the stimulus-response curve, particularly the curve slope or discontinuities in the curve as it can be seen in amyotrophic lateral sclerosis. Nevertheless, the delta between iMAX and motor threshold values might contain a similar information to the curve slope.
http://ift.tt/2yXXF1U
The insular cortex and QTc interval in HIV+ and HIV- individuals: Is there an effect of sympathetic nervous system activity?
The insular cortex and QTc interval in HIV+ and HIV- individuals: Was there the effect of sympathetic nervous system activity?
http://ift.tt/2xvnGBQ
Derivatizations of Sgc8-c aptamer to prepare metallic radiopharmaceuticals as imaging diagnostic agents: Syntheses, isolations and physicochemical characterizations
Abstract
Aptamers, oligonucleotides with the capability to bind to a target through non-covalent bonds with high affinity and specificity, have a great number of advantages as scaffold to prepare molecular imaging agents. In this sense, we have performed post-SELEX modifications of a truncated aptamer, Sgc8-c, which bind to protein tyrosine kinase 7 to obtain a specific molecular targeting probe for in vivo-diagnosis and -therapy. Herein, we describe the synthetic efforts to prepare conjugates between Sgc8-c and different metallic ions chelator-moieties in short times, high purities, and adequate yields. The selected chelator-moieties, derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 2-benzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 6-hydrazinonicotinic acid (HYNIC), were covalently attached at the 5′-aptamer position yielding the expected products which were stables in aqueous solution up to 75 °C and in typical aptamers-storages conditions at least for 30 days.
This article is protected by copyright. All rights reserved.
Post-SELEX modification on Sgc8-c aptamer, in order to prepare conjugate for furthrer transformations to radiopharmaceuticals, are described
Derivatizations of Sgc8-c aptamer to prepare metallic radiopharmaceuticals as imaging diagnostic agents: Syntheses, isolations and physicochemical characterizations
Estefanía Sicco, Jessica Báez, Jimena Margenat, Fernanda García, Manuel ibarra, Pablo Cabral, María Moreno, Hugo Cerecetto* and Victoria Calzada*
http://ift.tt/2lmOq64
3D-QSAR, Molecular Docking and ONIOM Studies on the Structure-Activity Relationships and Action Mechanism of Nitrogen-Containing Bisphosphonates
Abstract
Nitrogen-containing bisphosphonates (N-BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Understanding the structure-activity relationships and the action mechanisms of these bisphosphonates is instructive for the design and development of novel potent inhibitors. Here, a series of N-BPs inhibitors of human FPPS (hFPPS) were investigated by using a combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and three-layer ONIOM studies. The constructed 3D-QSAR model yielded a good correlation between the predicted and experimental activities. Based on the analysis of comparative molecular field analysis (CoMFA) contour maps, a series of novel N-BPs inhibitors were designed and ten novel potent N-BPs inhibitor candidates were screened out. Molecular docking and ONIOM (B3LYP/6-31+G*:PM6:Amber) calculations revealed that the inhibitors bound to the active site of hFPPS via hydrogen bonding interactions, hydrophobic interactions and cation-π interactions. Six novel N-BPs inhibitors with better biological activities and higher lipophilicity were further screened out from ten candidates based on the calculated interaction energy. This study will facilitate the discovery of novel N-BPs inhibitors with higher activity and selectivity.
This article is protected by copyright. All rights reserved.
A 3D-QSAR model was constructed for 53 N-BPs with the inhibition activities on hFPPS.
A series of novel N-BPs inhibitors were designed and six novel N-BPs inhibitors with better biological activities and higher lipophilicity were screened out.
Molecular docking and ONIOM (B3LYP/6-31+G*:PM6:Amber) calculations showed that the inhibitors bound to the active site of hFPPS via hydrogen bonding interactions, hydrophobic interactions and cation-π interactions.
http://ift.tt/2yaHeA8
No effect of comorbidities on the association between social deprivation and geographical access to the reference care center in the management of colon cancer
Patients with colon cancer in France exhibit one of the steepest socioeconomic survival gradients in Europe. Among the putative causes for this situation, comorbidities are frequently incriminated but evidence of this is lacking.
http://ift.tt/2hhTUuz
Long-term course of precancerous lesions arising in patients with gastric MALT lymphoma
To evaluate the prevalence and the long-term course of gastric precancerous lesions in patients with GML.
http://ift.tt/2iaPtRG
Profile of stroke patients treated at a rehabilitation centre in Bangladesh
Stroke is the leading cause of death and disability in Bangladesh. Rehabilitation services have not yet been integrated into the Bangladesh health system. Only a few non-governmental organisations provide reha...
http://ift.tt/2yR6yKQ
Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda
Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with...
http://ift.tt/2gPpWkp
Cytokines associated with Burkitt’s lymphoma in western Kenya
Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or Plasmodium falciparum are associated with immune h...
http://ift.tt/2yRkVis
Risk of cardiovascular events from current, recent, and cumulative exposure to abacavir among persons living with HIV who were receiving antiretroviral therapy in the United States: a cohort study
There is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates.
http://ift.tt/2xtv54S
PET-CT Image Fusion using Random Forest and À-trous Wavelet Transform
Summary
New image fusion rules for multimodal medical images are proposed in this work. Image fusion rules are defined by Random Forest (RF) learning algorithm and a translation-invariant à-trous wavelet transform (AWT). The proposed method is threefold. First, source images are decomposed into approximation and detail coefficients using AWT. Second, RF is used to choose pixels from the approximation and detail coefficients for forming the approximation and detail coefficients of the fused image. Lastly, inverse AWT (iAWT) is applied to reconstruct fused image. All experiments have been performed on 198 slices of both Computed Tomography (CT) and Positron Emission Tomography (PET) images of a patient. A traditional fusion method based on Mallat wavelet transform has also been implemented on these slices. A new image fusion performance measure along with four existing measures has been presented, which helps to compare the performance of two pixel level fusion methods. The experimental results clearly indicate that the proposed method outperforms the traditional method in terms of visual and quantitative qualities and the new measure is meaningful. This article is protected by copyright. All rights reserved.
http://ift.tt/2ia0YsK
Interagency Board releases recommended fentanyl exposure best practices
The board included best practices for PPE, decontamination and medical countermeasures
http://ift.tt/2y9Q7tu
Cost-effectiveness of ceftolozane/tazobactam plus metronidazole versus piperacillin/tazobactam as initial empiric therapy for the treatment of complicated intra-abdominal infections based on pathogen distributions drawn from national surveillance data in the United States
The prevalence of antimicrobial resistance among gram-negative pathogens in complicated intra-abdominal infections (cIAIs) has increased. In the absence of timely information on the infecting pathogens and the...
http://ift.tt/2gIzMRt
Population Pharmacokinetics of Exendin-(9-39) and Clinical Dose Selection in Patients with Congenital Hyperinsulinism
Summary
Aims
Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We reported the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and proposed the optimal dosing regimen for future clinical trials in neonates with HI.
Methods
182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using FOCE with interaction method in NONMEM. Exposure metrics (area under the curve [AUC] and maximum plasma concentration [Cmax]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies.
Results
Observed concentration-time profiles of exendin-(9-39) were described by a linear two-compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half-life for adult subjects with median weight of 69 kg were 11.8 L/hr and 1.81 hours, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC0-last at the NOAEL and predicted AUC0-inf using the PopPK model was 27 mg/kg/day intravenously.
Conclusions
This is the first study to investigate the PopPK of exendin-(9-39) in human. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin-(9-39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response.
http://ift.tt/2zU2t69
Long-term Live Imaging Device for Improved Experimental Manipulation of Zebrafish Larvae
http://ift.tt/2zcUfcn
A novel segmentation method for uneven lighting image with noise injection based on non-local spatial information and intuitionistic fuzzy entropy
Local thresholding methods for uneven lighting image segmentation always have the limitations that they are very sensitive to noise injection and that the performance relies largely upon the choice of the init...
http://ift.tt/2zSwKlT
Therapeutic Efficacy of Methazolamide Against Intermittent Hypoxia-Induced Excessive Erythrocytosis in Rats
High Altitude Medicine & Biology , Vol. 0, No. 0.
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Behind the wheel of an ambulance: Training needed
Fire and EMS agencies owe their crews, and the citizens they serve and protect, competent fire apparatus and ambulance driver/operators
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Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
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Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.
| Related Articles |
Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.
Viruses. 2017 Oct 25;9(11):
Authors: Wang X, Wang L, Huang X, Ma S, Yu M, Shi W, Qiao X, Tang L, Xu Y, Li Y
Abstract
Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences (p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.
PMID: 29068402 [PubMed - in process]
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Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review.
 | Related Articles |
Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review.
Curr Med Chem. 2017;24(27):3002-3009
Authors: Batash R, Asna N, Schaffer P, Francis N, Schaffer M
Abstract
BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials.
OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly.
METHOD: Systemic compilation of the relevant literature.
RESULTS & CONCLUSION: Today's treatments cannot cure GBM patients but only extend their overall survival. The use of chemoradiation, immunotherapy, and radio sensitizers as an adjuvant therapy cannot reduce the high rates of recurrence within a few months after treatment. Radiotherapy will remain the backbone of the treatment but new treatment modalities must be developed.
PMID: 28521700 [PubMed - indexed for MEDLINE]
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PARP Inhibitors in Prostate Cancer.
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PARP Inhibitors in Prostate Cancer.
Curr Treat Options Oncol. 2017 Jun;18(6):37
Authors: Ramakrishnan Geethakumari P, Schiewer MJ, Knudsen KE, Kelly WK
Abstract
OPINION STATEMENT: The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded "breakthrough designation" to develop the PARPi olaparib in treating this subset of metastatic PCa patients. The search for predictive biomarkers has expanded the realm of DNA repair genetic defects and combination genetic platforms are being evaluated as tools to assess potential "BRCAness" of tumors. Ongoing clinical trials seek to determine the optimal timing and sequence of using these agents in current PCa treatment algorithms. Combination strategies of PARPi with chemo-, radiation, and hormonal therapies, targeted agents, and immunotherapy are promising avenues of current research. Multi-center international collaborations in well-designed biomarker-driven clinical trials will be key to harness the potential of PARPi in managing a heterogeneous disease like prostate cancer.
PMID: 28540598 [PubMed - indexed for MEDLINE]
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Indoor Experimental Assessment of the Efficiency and Irradiance Spot of the Achromatic Doublet on Glass (ADG) Fresnel Lens for Concentrating Photovoltaics
The achromatic doublet on glass (ADG) Fresnel lens makes use of two materials with differing dispersion to reduce chromatic aberration and increase attainable concentration. In this paper, a protocol for the complete characterization of the ADG Fresnel lens is presented.
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Perspectives on the discovery of NOTCH2-specific inhibitors
Abstract
The Notch pathway is a cell-cell communication system where membrane-bound ligands interact with the extracellular region of Notch receptors to induce intracellular, downstream effects on gene expression. Aberrant Notch signaling promotes tumorigenesis, and the Notch pathway has tremendous potential for novel targeting strategies in cancer treatment. While γ-secretase inhibitors as Notch-inhibiting agents are already promising in clinical trials, they are highly non-specific with adverse side effects. One of the underlying challenges is that two of the four known human Notch paralogs, NOTCH1 and 2, share very high structural similarity but play opposing roles in some tumorigenesis pathways. This perspective explores the feasibility of developing Notch-specific small molecule inhibitors targeting the anti-NOTCH2 antibody binding epitopes or the 'S2-Leu plug-binding site' using a computer-aided drug discovery approach.
This article is protected by copyright. All rights reserved.
We review current Notch inhibitors of small molecules and expensive monoclonal antibodies.
Our computational modeling of the Notch proteins suggests that the S2 cleavage site, blocked by a conserved Leucine residue in the receptor's inactive state, is a plausible Notch-specific therapeutic site to target.
Synthetic antibody mimics present an attractive future drug modality to target specific Notch paralogs and replace monoclonal antibodies.
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Sample Preparation and Analysis of RNASeq-based Gene Expression Data from Zebrafish
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Disseminating and Sustaining Emergency Department Innovations for Older Adults: Good Ideas Deserve Better Policies
Older adults often visit the emergency department (ED) with chief complaints that understate or detract from their true complex health care needs. These needs are frequently missed because addressing them requires a time-consuming effort that is antithetical to the (necessarily) rapid, complaint-specific protocols of the ED. Key ED performance indices (e.g., length of stay; through-put) also create a disincentive against undertaking comprehensive geriatric assessments when not clearly germane to the chief complaint. However, ignoring these complex care issues can contribute to poor health outcomes. These visits often serve as sentinel events in the patient's health trajectory which irreversibly hastens loss of independence. Such encounters will only increase as the population ages.
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Air ambulance delivery and administration of 4-factor prothrombin complex concentrate is feasible and decreases time to anticoagulation reversal
Abstract
Objectives
To evaluate the feasibility, safety, and preliminary efficacy of four-factor prothrombin complex concentrate (4-factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin-associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4-factor PCC following transfer by air ambulance or ground without 4-factor PCC treatment (conventional arm).
Methods
Retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4-factor PCC from April 1st 2014 through June 30th 2016 were identified For this study, only transfer patients with an INR >1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, ICU length of stay and in-patient mortality between groups.
Results
Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤1.5 on ED arrival (proportion difference 0.82, 95% CI 0.64 to 0.92; p < 0.0001) and significantly reduced time to observed INR ≤1.5 (181 vs 541 minutes; p = 0.001). No differences were observed in thromboembolic complications or patient-centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale and higher intubation rates prior to transfer and treatment.
Conclusions
Dispatch of an air ambulance carrying 4-factor PCC with administration prior to transfer is feasible and leads to more rapid improvement in INR among patients with warfarin-associated major hemorrhage.
This article is protected by copyright. All rights reserved.
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Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for Adult T-cell Leukemia
Summary
ATL has a poor prognosis due to severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated-genome analysis has revealed mutations in many genes involved in the T-cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL-cell proliferation. We screened a siRNA library to examine signaling-pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL-cell proliferation. We therefore investigated the effect of mTOR inhibitors, including the dual inhibitors PP242 and AZD8055 and the mTORC1 inhibitors rapamycin and everolimus, on HTLV-1-infected-cell and ATL-cell lines. Both dual inhibitors inhibited the proliferation of all tested cell lines by inducing G1-phase cell-cycle arrest and subsequent cell apoptosis, whereas the effects of the two mTORC1 inhibitors were limited, as they did not induce cell apoptosis. In the ATL-cell lines and in the primary ATL samples, both dual inhibitors inhibited phosphorylation of AKT at serine-473, a target of mTORC2, as well as that of S6K, whereas the mTORC1 inhibitors only inhibited mTORC1. Furthermore, AZD8055 more significantly inhibited the in vivo growth of the ATL-cell xenografts than did everolimus. These results indicate that the PI3K/mTOR pathway is critical to ATL-cell proliferation and might thus be a new therapeutic target in ATL.
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Hepatocyte DUSP14 maintains metabolic homeostasis and suppresses inflammation in the liver
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Despite such public and clinical health importance, very few effective therapies are currently available for NAFLD. Herein, we reported a protective function and the underlying mechanism of dual-specificity phosphatase 14 (DUSP14) in NAFLD and related metabolic disorders. Insulin resistance, hepatic lipid accumulation and concomitant inflammatory responses, which are key pathological processes involved in NAFLD development, were significantly ameliorated by hepatocyte-specific DUSP14 overexpression (DUSP14-HTG) in high-fat diet (HFD)-induced or genetically obese mouse models. By contrast, specific DUSP14 deficiency in hepatocytes (DUSP14-HKO) aggravated these pathological alterations. We provided mechanistic evidence that DUSP14 directly binds to and dephosphorylates TGFβ-activated kinase 1 (TAK1), resulting in the reduced activation of TAK1 and its downstream signaling molecules JNK, p38 and NF-κB. This effect was further evidenced by the finding that inhibiting TAK1 activity effectively attenuated the deterioration of glucolipid metabolic phenotype in DUSP14-HKO mice challenged by HFD administration. Furthermore, we identified that both the binding domain and the phosphatase activity of DUSP14 are required for its protective role against hepatic steatosis, as interruption of the DUSP14-TAK1 interaction abolished the mitigative effects of DUSP14.
Conclusions: Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. This article is protected by copyright. All rights reserved.
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20 more thoughts only a paramedic will understand
By EMS1 Staff Paramedics are a special breed. There are many thoughts only you will understand, and there's absolutely nothing wrong with that. We've all experienced the tones dropping before a shift change and have thought to ourselves, "Really"" And you haven't been in EMS long enough if you don't yell "Clear right!" when you're driving off-duty. Our Facebook ...
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Training and Assessing Critical Airway, Breathing and Hemorrhage Control Procedures for Trauma Care: Live Tissue versus Synthetic Models
Abstract
Introduction
Optimal teaching and assessment methods and models for emergency airway, breathing and hemorrhage interventions are not currently known. The University of Minnesota Combat Casualty Training consortium (UMN CCTC) was formed to explore the strengths and weaknesses of synthetic training models (STMs) versus Live tissue (LT) models. In this study, we compare the effectiveness of best in class STMs versus an anesthetized caprine (goat) model for training and assessing 7 procedures: Junctional hemorrhage control, Tourniquet (TQ) placement, Chest seal, Needle thoracostomy (NCD), Nasopharyngeal airway (NPA), Tube thoracostomy, and Cricothyrotomy (Cric).
Methods
Army combat medics were randomized to one of four groups: 1) Live tissue trained – live tissue tested (LT-LT), 2) live tissue trained – synthetic training model tested (LT-STM), 3) synthetic training model trained – live tissue tested (STM-LT), 4) synthetic training model trained – synthetic training model tested (STM-STM). Participants trained in small groups for 3-4 hours and were evaluated individually. LT-LT was the "control" to which other groups were compared, as this is the current military pre-deployment standard. The mean procedural scores (PS) were compared using a pairwise t-test with a Dunnett's correction. Logistic regression was used to compare critical fails (CF) and skipped tasks.
Results
There were 559 subjects included. Junctional hemorrhage control revealed no difference in CFs, but LT tested subjects (LT-LT and STM-LT) skipped this task more than STM tested subjects (LT-STM and STM-STM) (p<0.05), and STM-STM had higher PS than LT-LT (p<0.001). For TQ, both STM tested groups (LT-STM and STM-STM) had more CFs than LT-LT (p<0.001) and LT-STM had lower PS than LT-LT (p<0.05). No differences were seen for chest seal. For NCD, LT-STM had greater CFs than LT-LT (p=0.001), and lower PSs (p=0.001). There was no difference in CFs for NPA, but all groups had worse PS versus LT-LT (p<0.05). For Cric, we were underpowered; STM-LT trended towards more CFs (p=0.08), and STM-STM had higher PSs than LT-LT (p<0.01). Tube thoracostomy revealed STM-LT had higher CFs than LT-LT (p<0.05), but LT-STM had lower PS (p<0.05). An interaction effect (making the subjects who trained and tested on different models more likely to CF) was only found for Tourniquet, chest seal and Cric, however, of these 3 procedures, only TQ demonstrated any significant difference in CF rates.
Conclusion
Training on STM or LT did not demonstrate a difference in subsequent performance for 5 of 7 procedures (junctional hemorrhage, TQ, chest seal, NPA and NCD). Until synthetic training models are developed with improved anthropomorphic and tissue fidelity, there may still be a role for LT for training tube thoracostomy and potentially cricothyrotomy. For assessment, our STM appears more challenging for TQ and potentially for NCD than LT. For junctional hemorrhage, the increased "skips" with LT may be explained by the differences in anatomic fidelity. While these results begin to uncover the effects of training and assessing these procedures on various models, further study is needed to ascertain how well performance on an STM or LT model translates to the human model.
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Lignin degradation: microorganisms, enzymes involved, genomes analysis and evolution
Abstract
Extensive research efforts have been dedicated to describing degradation of wood, which is a complex process; hence, microorganisms have evolved different enzymatic and non-enzymatic strategies to utilize this plentiful plant material. This review describes a number of fungal and bacterial organisms which have developed both competitive and mutualistic strategies for the decomposition of wood and to thrive in different ecological niches. Through the analysis of the enzymatic machinery engaged in wood degradation, it was possible to elucidate different strategies of wood decomposition which often depend on ecological niches inhabited by given organism. Moreover, a detailed description of low molecular weight compounds is presented, which gives these organisms not only an advantage in wood degradation processes, but seems rather to be a new evolutionatory alternative to enzymatic combustion. Through analysis of genomics and secretomic data, it was possible to underline the probable importance of certain wood-degrading enzymes produced by different fungal organisms, potentially giving them advantage in their ecological niches. The paper highlights different fungal strategies of wood degradation, which possibly correlates to the number of genes coding for secretory enzymes. Furthermore, investigation of the evolution of wood-degrading organisms has been described.http://ift.tt/2zK10P4
Drift and Behavior of E. coli Cells
Chemotaxis of the bacterium Escherichia coli is well understood in shallow chemical gradients, but its swimming behavior remains difficult to interpret in steep gradients. By focusing on single-cell trajectories from simulations, we investigated the dependence of the chemotactic drift velocity on attractant concentration in an exponential gradient. Whereas maxima of the average drift velocity can be interpreted within analytical linear-response theory of chemotaxis in shallow gradients, limits in drift due to steep gradients and finite number of receptor-methylation sites for adaptation go beyond perturbation theory.
http://ift.tt/2yVrMa6
Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy
Abstract
Purpose
Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains.
Methods
Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL).
Results
Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28–0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44–0.51) in CRC patients.
Conclusions
No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory.
Trial registration
The study was registered with clinicaltrials.gov (trial registration: NCT00188331).
Implications for cancer survivors
Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls.
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Risk factors contributing to a low darunavir plasma concentration
Summary
Darunavir is an efficacious drug, however pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till December 2014 of HIV-infected individuals treated in the outpatient clinic of the University Medical Center Groningen were retrospectively reviewed. The first darunavir plasma concentration of patients within 8 weeks after initiation of darunavir therapy was selected. A dichotomal logistic regression analysis was conducted to select the set of variables best predicting a darunavir concentration below median population pharmacokinetic curve. In total 113 patients were included. The variables best predicting a darunavir concentration besides food intake included age together with estimated glomerular filtration rate (Hosmer and Lemeshow Test p=0.945, Nagelkerke R Square 0.284). Systematic evaluation of TDM results may help to identify patients at risk for low drug exposure.
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No impact of perioperative blood transfusion on prognosis after curative resection for hepatocellular carcinoma: a propensity score matching analysis
Abstract
Background
The relationship between perioperative blood transfusion and long-term survival after curative resection for hepatocellular carcinoma (HCC) remains controversial. The aim of the present study was to investigate the impact of blood transfusion on the long-term prognosis of HCC patients.
Methods
Patients with primary HCC who underwent a curative hepatectomy from 2003 to 2011 were enrolled and then retrospectively studied. The clinicopathologic characteristics between patients in the blood transfusion and non-transfusion groups were matched using a propensity score matching (PSM) analysis. Univariate and multivariate Cox regression analyses were used to identify whether perioperative blood transfusion affects long-term survival after resection for HCC.
Results
A total of 374 patients were enrolled and 113 patients received perioperative transfusions. The 1-, 3- and 5-year disease-free and overall survival rates of the entire cohort were 65.0, 37.3 and 23.9%, and 90.9, 70.7 and 57.5%, respectively. The disease-free and overall survival rates of the blood transfusion group were significantly worse than the disease-free and overall survival rates of the non-transfusion group in the entire cohort (p < 0.001, p < 0.001). However, the differences in the survival rates between the two groups were no longer significant after PSM (p = 0.067, p = 0.105). Multivariate Cox analyses showed that perioperative blood transfusion was not an independent predictor of disease-free and overall survival in the propensity-matched cohort (p = 0.154, p = 0.667).
Conclusions
The present study demonstrates that perioperative blood transfusion has no impact on disease-free and overall survival after curative resection for HCC.
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A switch of chlorinated substrate causes emergence of a previously undetected native Dehalobacter population in an established Dehalococcoides -dominated chloroethene-dechlorinating enrichment culture
Abstract
Chlorobenzenes are soil and groundwater pollutants of concern which can be reductively dehalogenated by organohalide-respiring bacteria from the genera Dehalococcoides and Dehalobacter. The bioaugmentation culture KB-1 harbours Dehalococcoides mccartyi spp. that reductively dehalogenate trichloroethene to ethene. It contains more than 30 reductive dehalogenase genes; some of them are highly similar to genes found in the chlorobenzene-respiring Dehalococcoides mccartyi strain CBDB1. We explored the chlorobenzene dehalogenation capability of the KB-1 enrichment culture using 1,2,4-trichlorobenzene (1,2,4-TCB). We achieved adaptation of KB-1 to 1,2,4-TCB which is dehalogenated to a mixture of dichlorobenzenes, and subsequently to monochlorobenzene and benzene. Surprisingly, a native Dehalobacter population, and not a Dehalococcoides population, couples the dechlorination of 1,2,4-TCB to growth achieving an average yield of 1.1 ± 0.6 × 1013 cells per mole of Cl− released. Interestingly, the dechlorination of 1,2,4-TCB occurs alongside the complete dechlorination of trichloroethene to ethene in cultures fed both electron acceptors. Dehalobacter was not previously identified as a major player in KB-1, but its ecological niche was favoured by the introduction of 1,2,4-TCB. Based on 16S rRNA phylogeny, Dehalobacter populations seem to cluster into specialized clades, and are likely undergoing substrate specialization as a strategy to reduce competition for electron acceptors.http://ift.tt/2yb2mG6
Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
Abstract
Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophagy to increase the ability to get rid of the unwanted tau aggregates. One of the key controllers of autophagy is mTOR. Blocking mTOR leads to stimulation of autophagy. Recently, unravelling molecular structure of mTOR showed that it is formed of two subunits: mTORC1/C2. So, blocking both subunits of mTOR seems more attractive as it will explore all abilities of mTOR molecule. In the present study, we report using pp242 which is a dual mTORC1/C2 blocker in cellular model of tauopathy using LUHMES cell line. Adding fenazaquin to LUHMES cells induced tauopathy in the form of increased phospho tau aggregates. Moreover, fenazaquin treated cells showed the characteristic somatic redistribution of tau. PP242 use in the present tauopathy model reversed the pathology significantly without observable cellular toxicity for the used dosage of 1000 nM. The present study suggests the possible use of pp242 as a dual mTOR blocker to treat tauopathy.
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Antibiotic treatment disrupts bacterial communities in the colon and rectum of SIV-infected macaques
Abstract
Antibiotic therapies are known to disrupt gastrointestinal (GI) bacterial communities. HIV and pathogenic simian immunodeficiency virus (SIV) infections have also been associated with disrupted GI bacterial communities. We administered a combination antibiotic therapy to six SIV-infected rhesus macaques (RM) and collected colon biopsies, stool samples, and rectal swabs before and after antibiotics, and evaluated the bacterial communities at each sample site using high-throughput 16S rRNA gene sequencing. The colon mucosa and stool samples displayed different bacterial communities, while the rectal swabs showed a mixture of the mucosal and stool-associated bacteria. Antibiotics disrupted the native bacterial communities at each sample site. The colon mucosa showed depleted abundances of the dominant Helicobacteraceae, while we found depleted abundances of the dominant Ruminococcaceae sp. in the stool. The rectal swabs showed similar trends as the colon mucosa, but were more variable. After the antibiotic treatment, there were increased abundances of similar taxa of facultative anaerobic bacteria, including Lactobacillaceae and Enterobacteriaceae at each sample site.http://ift.tt/2y9yNoo
Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma
Abstract
Aims
We aimed to identify the prognostic factors of uterine leiomyosarcoma (ULMS).
Methods and results
We reviewed 6160 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expressions of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. In addition, mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (p<0.0001), older age (p=0.0244) and IMP3 expression (p=0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (p<0.0001) and IMP3 (p=0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study.
Conclusions
IMP3 expression in ULMS could be a marker of a poor prognosis.
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New Research From Psychological Science
Read about the latest research published in Psychological Science:
Educational Attainment and Personality Are Genetically Intertwined
René Mõttus, Anu Realo, Uku Vainik, Jüri Allik, and Tõnu Esk
In this study, the researchers examined whether phenotypic variation in personality traits is associated with polygenic propensity for educational attainment. The researchers examined more than 3,000 Estonian adults who were part of the Estonian Biobank cohort. The participants gave a blood sample for DNA testing, reported their highest level of educational attainment, and completed an assessment of personality domains of the five-factor model and their 30 facets. The researchers also collected personality ratings of participants provided by informants (e.g., spouse, friend, child, or sibling). The researchers found that the education polygenic scores — an estimate of molecular-genetic propensity for education — were correlated with various personality traits, especially those in the neuroticism and openness domains. This correlation closely mirrored the relationship between these traits and phenotypic education. The researchers indicate that there are many possible interpretations of these findings and that more research is needed.
Reprioritization of Features of Multidimensional Objects Stored in Visual Working Memory
Young Eun Park, Jocelyn L. Sy, Sang Wook Hong, and Frank Tong
Most objects people come across in their daily lives have several different features. The integrated-object hypothesis suggests that all the features of an object are bound together in working memory and stored in an integrated format. The researchers examined whether the individual features of an object that has already been encoded can be unbound during the maintenance stage of visual working memory. To test this, participants, in the first of several studies, viewed sine gratings that varied in color and orientation. After viewing the gratings, participants were shown a neutral cue or a cue that indicated whether their memory was likely to be tested for the color of the grating or the orientation of the grating. After a variable length of time, participants were asked to indicate either the color or the orientation of the stimuli. The researchers found enhanced working memory performance for the feature that was prioritized; however, this boost was associated with decreased performance for the deprioritized feature. This finding challenges the assumption that features of an object are obligatorily represented as an integrated object in visual working memory.
Categories and Constraints in Causal Perception
Jonathan F. Kominsky, Brent Strickland, Annie E. Wertz, Claudia Elsner, Karen Wynn, and Frank C. Keil
In the real world, when an object (A) collides with another object (B), it is unusual to see object B moving at a faster speed than object A — unless object B is self-propelled. Research on casual perception finds that people are sensitive to this, categorizing events in which object B moves faster than object A as "triggering" or "releasing" events, and events in which object B moves slower than object A as "launching" events. The researchers examined whether there is a distinction in causal perception between these two types of events by having participants view pairs of disks (A and B) involved in causal or noncausal events in which each disk in the pair moved at the same speed or at different speeds (disk A moves faster than disk B or vice versa). The researchers observed categorical boundaries within causal perception in that incidences in which disk B moved faster than disk A were viewed as being categorically different than symmetrical-speed events or events in which disk A moved faster than disk B. This categorical distinction was seen in children as young as 7 to 9 months old, suggesting that this may be an early-developing component of causal perception.
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The Size of Ruptured Intracranial Aneurysms
Abstract
Purpose
There is a controversy concerning the risk of rupture of small intracranial aneurysms. We sought to determine the size and morphological features of ruptured intracranial aneurysms.
Material and Methods
The hospital files and images from all patients referred during one decade (2007–2016) to a specialized neurovascular center were retrospectively reviewed. Neck diameter, fundus depth and width as well as neck width based on catheter angiography were measured. Aneurysm morphology was classified as either regular, lobulated, irregular or fusiform.
Results
A total of 694 consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) were identified (65.9% female, median age 54.3 years). The anterior communicating artery (AcomA) was the most frequent location of ruptured aneurysms. The medians for aneurysm depth, width and neck diameter were 5 mm, 4.5 mm and 3 mm, respectively. A regular contour of the aneurysm sac was found in 19%.
Conclusion
The majority of aSAH are caused by small intracranial aneurysms. There is no safety margin in terms of small aneurysm size of regular shape without daughter aneurysms. Treatment should also be offered to patients with small, regularly shaped intracranial aneurysms, together with an empirical risk-benefit assessment.
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Behind the wheel of an ambulance: Training needed
Fire and EMS agencies owe their crews, and the citizens they serve and protect, competent fire apparatus and ambulance driver/operators
http://ift.tt/2gHOJTS
Drift and Behavior of E. coli Cells
Chemotaxis of the bacterium Escherichia coli is well understood in shallow chemical gradients, but its swimming behavior remains difficult to interpret in steep gradients. By focusing on single-cell trajectories from simulations, we investigated the dependence of the chemotactic drift velocity on attractant concentration in an exponential gradient. Whereas maxima of the average drift velocity can be interpreted within analytical linear-response theory of chemotaxis in shallow gradients, limits in drift due to steep gradients and finite number of receptor-methylation sites for adaptation go beyond perturbation theory.
http://ift.tt/2yVrMa6
Determining counselling communication strategies associated with successful quits in the National Health Service community pharmacy Stop Smoking programme in East London: a focused ethnography using recorded consultations
Objectives
To determine communication strategies associated with smoking cessation in the National Health Service community pharmacy Stop Smoking programme.
Setting11 community pharmacies in three inner east London boroughs.
Participants9 stop smoking advisers and 16 pairs of smokers who either quit or did not quit at 4 weeks, matched on gender, ethnicity, age and smoking intensity.
Method1–3 audio-recorded consultations between an adviser and each pair member over 5–6 weeks were analysed using a mixed-method approach. First a content analysis was based on deductive coding drawn from a theme-oriented discourse analysis approach and the Roter Interaction Analysis System. Core themes were identified through this quantification to explore in detail the qualitative differences and similarities between quitters and non-quitters.
ResultsQuantitative analysis revealed advisers used a core set of counselling strategies that privileged the 'voice of medicine' and often omitted explicit motivational interviewing. Smokers tended to quit when these core strategies were augmented by supportive talk, clear permission for smokers to seek additional support from the adviser between consultations, encouragement for smokers to use willpower. The thematic analysis highlighted the choices made by advisers as to which strategies to adopt and the impacts on smokers. The first theme 'Negotiating the smoker–adviser relationship' referred to adviser judgements about the likelihood the smoker would quit. The second theme, 'Roles of the adviser and smoker in the quit attempt', focused on advisers' counselling strategies, while the third theme, 'Smoker and adviser misalignment on reasons for smoking, relapsing and quitting', concerned inconsistencies in the implementation of National Centre for Smoking Cessation and Training recommendations.
DiscussionAdvisers in community pharmacies should use the advantages of their familiarity with smokers to ensure appropriate delivery of patient-centred counselling strategies and reflect on the impact on their counselling of early judgements of smoker success.
http://ift.tt/2i94PGi
Cost-effectiveness of the faecal immunochemical test at a range of positivity thresholds compared with the guaiac faecal occult blood test in the NHS Bowel Cancer Screening Programme in England
Objectives
Through the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP), men and women in England aged between 60 and 74 years are invited for colorectal cancer (CRC) screening every 2 years using the guaiac faecal occult blood test (gFOBT). The aim of this analysis was to estimate the cost–utility of the faecal immunochemical test for haemoglobin (FIT) compared with gFOBT for a cohort beginning screening aged 60 years at a range of FIT positivity thresholds.
DesignWe constructed a cohort-based Markov state transition model of CRC disease progression and screening. Screening uptake, detection, adverse event, mortality and cost data were taken from BCSP data and national sources, including a recent large pilot study of FIT screening in the BCSP.
ResultsOur results suggest that FIT is cost-effective compared with gFOBT at all thresholds, resulting in cost savings and quality-adjusted life years (QALYs) gained over a lifetime time horizon. FIT was cost-saving (p<0.001) and resulted in QALY gains of 0.014 (95% CI 0.012 to 0.017) at the base case threshold of 180 µg Hb/g faeces. Greater health gains and cost savings were achieved as the FIT threshold was decreased due to savings in cancer management costs. However, at lower thresholds, FIT was also associated with more colonoscopies (increasing from 32 additional colonoscopies per 1000 people invited for screening for FIT 180 µg Hb/g faeces to 421 additional colonoscopies per 1000 people invited for screening for FIT 20 µg Hb/g faeces over a 40-year time horizon). Parameter uncertainty had limited impact on the conclusions.
ConclusionsThis is the first published economic analysis of FIT screening in England using data directly comparing FIT with gFOBT in the NHS BSCP. These results for a cohort starting screening aged 60 years suggest that FIT is highly cost-effective at all thresholds considered. Further modelling is needed to estimate economic outcomes for screening across all age cohorts simultaneously.
http://ift.tt/2gIwPQM
Randomised controlled trial of the clinical and cost-effectiveness of a peer-delivered self-management intervention to prevent relapse in crisis resolution team users: study protocol
Introduction
Crisis resolution teams (CRTs) provide assessment and intensive home treatment in a crisis, aiming to offer an alternative for people who would otherwise require a psychiatric inpatient admission. They are available in most areas in England. Despite some evidence for their clinical and cost-effectiveness, recurrent concerns are expressed regarding discontinuity with other services and lack of focus on preventing future relapse and readmission to acute care. Currently evidence on how to prevent readmissions to acute care is limited. Self-management interventions, involving supporting service users in recognising and managing signs of their own illness and in actively planning their recovery, have some supporting evidence, but have not been tested as a means of preventing readmission to acute care in people leaving community crisis care. We thus proposed the current study to test the effectiveness of such an intervention. We selected peer support workers as the preferred staff to deliver such an intervention, as they are well-placed to model and encourage active and autonomous recovery from mental health problems.
Methods and analysisThe CORE (CRT Optimisation and Relapse Prevention) self-management trial compares the effectiveness of a peer-provided self-management intervention for people leaving CRT care, with treatment as usual supplemented by a booklet on self-management. The planned sample is 440 participants, including 40 participants in an internal pilot. The primary outcome measure is whether participants are readmitted to acute care over 1 year of follow-up following entry to the trial. Secondary outcomes include self-rated recovery at 4 and at 18 months following trial entry, measured using the Questionnaire on the Process of Recovery. Analysis will follow an intention to treatment principle. Random effects logistic regression modelling with adjustment for clustering by peer support worker will be used to test the primary hypothesis.
Ethics and disseminationThe CORE self-management trial was approved by the London Camden and Islington Research Ethics Committee (REC ref: 12/LO/0988). A Trial Steering Committee and Data Monitoring Committee oversee the progress of the study. We will report on the results of the clinical trial, as well as on the characteristics of the participants and their associations with relapse.
Trial registration numberISRCTN 01027104;pre-results stage.
http://ift.tt/2i8saYQ
Cohort profile: a nationwide cohort of Finnish military recruits born in 1958 to study the impact of lifestyle factors in early adulthood on disease outcomes
Purpose
The cohort was set up to study the impact of lifestyle factors in early adulthood on disease outcomes, with a focus on assessing the influence of body composition and physical performance in early adulthood on subsequent cancer risk.
ParticipantsMen born in 1958 who performed their military service between the ages of 17 and 30 years were included in this study (n=31 158). They were eligible for military service if they were healthy or had only minor health problems diagnosed at the beginning of their service. Men with chronic illnesses requiring regular medication or treatment were not eligible for service. Comprehensive health data including diagnosed illnesses, anthropometric measures and health behaviour were collected at the beginning and at the end of military service, including data from medical check-ups.
Findings to dateDuring the follow-up, 1124 new cancer cases were diagnosed between baseline (ie, end of the military service for each individual) and end of the year 2014. In the end of the follow-up, 91% of the study participants were still alive. Overweight (body mass index (BMI) ≥25 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with an overall increased risk of cancer. A good or excellent physical condition significantly reduced cancer risk.
Future plansThe dataset offers the possibility of linkage with other databases, such as the Finnish Cancer Registry (eg, primary site of the tumour, morphology, time of detection, spreading and primary treatment), vital statistics (date of emigration or deaths), censuses (socioeconomic indicators), hospital discharge data (comorbidity) and population surveys (life habits).
http://ift.tt/2i92H1l
Combination of obstructive sleep apnoea and insomnia treated by continuous positive airway pressure with the SensAwake pressure relief technology to assist sleep: a randomised cross-over trial protocol
Introduction
Obstructive sleep apnoea (OSA) is a common sleep breathing disorder affecting up to 17% of the middle-aged population. Continuous positive airway pressure (CPAP) is the primary treatment for patients with OSA, but acceptance and adherence to therapy is suboptimal in specific subgroups particularly those with insomnia or poor sleep quality (40%–80% of patients with OSA). Pressure intolerance, particularly during periods of wakefulness, inhibiting sleep onset or return to sleep, is one reason for poor CPAP adherence. AutoCPAPs continually monitor airflow changes and only increase the pressure when the upper airway requires it. Reducing the pressure during wakefulness-sleep transition and wakefulness-after-sleep-onset (WASO) may improve therapy comfort and potentially adherence without compromising therapy efficacy. We hypothesise that SensAwake, a pressure relief function that reduces CPAP pressure on the transition from sleep to wakefulness and on WASO, may improve objective sleep quality.
Methods and analysisThis is a multicentre, randomised double-blind crossover clinical trial on patients with both OSA and insomnia. Insomnia is defined as Insomnia Severity Index >15 at screening. Baseline data, including actigraphy, are collected for 1 week before randomisation (1:1) to either conventional AutoCPAP or AutoCPAP with SensAwake for 4 weeks. After an evaluation visit, patients are switched to the other treatment arm for a further 4 weeks. Allowing for 20% dropout, 48 patients are required. If applicable, repeated measures analysis of variance will be used to assess differences in WASO measured by actigraphy (primary outcome), other actigraphy measures, AutoCPAP compliance, subjective questionnaire scores (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Short-Form 12 Health Survey) and 24 hours blood pressure (secondary outcomes).
Ethics and disseminationThe protocol was approved by the regional Ethics Committee (CPP Sud-Est–V, IRB N°6705) on 9 December 2015, is registered on ClincalTrials.gov (NCT02721329) and started in June 2016 with expected publication of primary outcome results in 2018.
Trial registration numberNCT0272132; Pre-results.
http://ift.tt/2gJmnsv
Prevalence and time trends in overweight and obesity among urban women: an analysis of demographic and health surveys data from 24 African countries, 1991-2014
Objective
To examine the prevalence and trends in overweight and obesity among non-pregnant urban women in Africa over the past two and a half decades.
DesignCross-sectional surveys conducted between 1991 and 2014.
SettingsDemographic and Health Surveys (DHS), repeated cross-sectional data collected in 24 African countries.
ParticipantsAdult non-pregnant women aged 15–49 years. The earlier DHS collected anthropometric data on only those women who had children aged 0–5 years. The main analyses were limited to this subgroup. The participants were classified as overweight (25.0–29.9 kg/m2) and obese (≥30.0 kg/m2).
ResultsThe prevalence of overweight and obesity among women increased in all the 24 countries. Trends were statistically significant in 17 of the 24 countries in the case of obesity and 13 of the 24 for overweight. In Ghana, overweight almost doubled (p=0.001) while obesity tripled (p=0.001) between 1993 and 2014. Egypt has the highest levels of overweight and obesity at 44% (95% CI 42%, 46.5%) and 39% (95% CI 36.6%, 41.8%), respectively, in 2014 and the trend showed significant increase (p=0.005) from 1995 levels. Also, obesity doubled in Kenya, Benin, Niger, Rwanda, Ivory Coast and Uganda, while tripled in Zambia, Burkina Faso, Mali, Malawi and Tanzania. Ethiopia and Madagascar had the lowest prevalence of both obesity and overweight, with overweight ranging from 7% to 12% and obesity from 1% to 4%.
ConclusionsOverweight and obesity are increasing among women of reproductive age in urban Africa, with obesity among this age group having more than doubled or tripled in 12 of the 24 countries. There is an urgent need for deliberate policies and interventions to encourage active lifestyles and healthy eating behaviour to curb this trend in urban Africa.
http://ift.tt/2gI09H1
Child maltreatment as a predictor of adult physical functioning in a prospective British birth cohort
Objective
Child maltreatment (abuse and neglect) has established associations with mental health; however, little is known about its relationship with physical functioning. Physical functioning (ie, the ability to perform the physical tasks of daily living) in adulthood is an important outcome to consider, as it is strongly associated with an individual's ability to work, and future disability and dependency. We aimed to establish whether maltreatment was associated with physical functioning, independent of other early-life factors.
Setting1958 British birth cohort.
Participants8150 males and females with data on abuse and who participated at age 50 years.
Outcome measuresThe primary outcome was poor physical functioning at 50 years (<65 on the Short-Form 36 survey physical functioning subscale). Secondary outcomes included mental health and self-reported health at 50 years.
Results23% of participants reported at least one type of maltreatment; 12% were identified with poor physical functioning. Neglect (ORadj 1.55, 95% CI 1.24 to 1.93), psychological abuse (ORadj 1.49, 1.17–1.88) and sexual abuse (ORadj 2.56, 1.66–3.96) were associated with poor physical functioning independent of other maltreatments and covariates, including childhood social class, birth weight and childhood illness. Odds of poor physical functioning increased with multiple types of maltreatment (ptrend <0.001); ORadj ranged from 1.49 (1.23–1.82) for a single type to 2.09 (1.53–2.87) for those reporting > 3 types of maltreatment, compared with those with none. Associations of similar magnitude were observed for mental and self-reported health outcomes.
ConclusionsChild neglect, psychological and sexual abuse were associated with poor physical functioning at 50 years, with accumulating risk for those with multiple types of maltreatment. Associations were independent of numerous early-life factors and were comparable in magnitude to those observed for mental health and self-rated health. Prevention or alleviation of the ill effects of maltreatment could be an effective policy intervention to promote healthy ageing.
http://ift.tt/2i94ljs
Oxygen-15 labeled CO 2 , O 2 , and CO PET in small animals: evaluation using a 3D-mode microPET scanner and impact of reconstruction algorithms
Abstract
Background
Positron emission tomography (PET) studies using 15O-labeled CO2, O2, and CO have been used in humans to evaluate cerebral blood flow (CBF), the cerebral oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood volume (CBV), respectively. In preclinical studies, however, PET studies using 15O-labeled gases are not widely performed because of the technical difficulties associated with handling labeled gases with a short half-life. The aims of the present study were to evaluate the scatter fraction using 3D-mode micro-PET for 15O-labeled gas studies and the influence of reconstruction algorithms on quantitative values.
Nine male SD rats were studied using the steady state inhalation method for 15O-labeled gases with arterial blood sampling. The resulting PET images were reconstructed using filtered back projection (FBP), ordered-subset expectation maximization (OSEM) 2D, or OSEM 3D followed by maximum a posteriori (OSEM3D-MAP). The quantitative values for each brain region and each reconstruction method were calculated by applying different reconstruction methods.
Results
The quantitative values for the whole brain as calculated using FBP were 46.6 ± 12.5 mL/100 mL/min (CBF), 63.7 ± 7.2% (OEF), 5.72 ± 0.34 mL/100 mL/min (CMRO2), and 5.66 ± 0.34 mL/100 mL (CBV), respectively. The CBF and CMRO2 values were significantly higher when the OSEM2D and OSEM3D-MAP reconstruction methods were used, compared with FBP, whereas the OEF values were significantly lower when reconstructed using OSEM3D-MAP.
Conclusions
We evaluated the difference in quantitative values among the reconstruction algorithms using 3D-mode micro-PET. The iterative reconstruction method resulted in significantly higher quantitative values for CBF and CMRO2, compared with the values calculated using the FBP reconstruction method.
http://ift.tt/2gGsyx6
Safety, pharmacokinetics, metabolism and radiation dosimetry of 18 F-tetrafluoroborate ( 18 F-TFB) in healthy human subjects
Abstract
Background
18F-Tetrafluoroborate (18F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18F-TFB in healthy human subjects.
Methods
18F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18F-TFB (333–407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety.
Results
18F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant).
Conclusions
This initial study in healthy human subjects showed 18F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.
http://ift.tt/2i8AVC5
Image Enhancement Variational Methods for Enabling Strong Cost Reduction in OLED-based Point-of-Care Immunofluorescent Diagnostic Systems
Summary
Objective:Immunofluorescence diagnostic systems cost is often dominated by high-sensitivity, low-noise CCD-based cameras which are used to acquire the fluorescence images. In this paper we investigate the use of low-cost CMOS sensors in a point-of-care immunofluorescence diagnostic application for the detection and discrimination of four different serotypes of the Dengue virus in a set of human samples. Methods: A two-phase post-processing software pipeline is proposed which consists in a first image enhancement stage for resolution increasing and segmentation, and a second diagnosis stage for the computation of the output concentrations. Results: blackWe present a novel variational coupled model for the joint super-resolution and segmentation stage, and an automatic innovative image analysis for the diagnosis purpose. A specially designed Forward Backward-based numerical algorithm is introduced and its convergence is proved under mild conditions. We present results on a cheap prototype CMOS camera compared with the results of a more expensive CCD device, for the detection of the Dengue virus with a low-cost OLED light source. The combination of the CMOS sensor and the developed post-processing software allows to correctly identify the different Dengue serotype using an automatized procedure. Conclusions: The results demonstrate that our diagnostic imaging system enables camera cost reduction up to 99%, at an acceptable diagnostic accuracy, with respect to the reference CCD-based camera system. The correct detection and identification of the Dengue serotypes has been confirmed by standard diagnostic methods (RT-PCR and ELISA). This article is protected by copyright. All rights reserved.
http://ift.tt/2zchDa7
Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics
Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality and treatment choices are often complex. With increased accessibility of next-generation sequencing the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a next-generation sequencing PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. 27 participants were recruited and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study demonstrates the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.
http://ift.tt/2zSL4ee
Recent Progress on Antimonene: A New Bidimensional Material
Abstract
Antimonene, defined in sensu stricto as a single layer of antimony atoms, is recently the focus of numerous theoretical works predicting a variety of interesting properties and is quickly attracting the attention of the scientific community. However, what places antimonene in a different category from other 2D crystals is its strong spin–orbit coupling and a drastic evolution of its properties from the monolayer to the few-layer system. The recent isolation of this novel 2D material pushes the interest for antimonene even further. Here, a review of both theoretical predictions and experimental results is compiled. First, an account of the calculations anticipating an electronic band structure suitable for optoelectronics and thermoelectric applications in monolayer form and a topological semimetal in few-layer form is given. Second, the different approaches to produce antimonene—mechanical and liquid phase exfoliation, and epitaxial growth methods—are reviewed. In addition, this work also reports the main characterization techniques used to study this exotic material. This review provides insights for further exploring the appealing properties of antimonene and puts forward the opportunities and challenges for future applications from (opto)electronic device fabrication to biomedicine.
Antimonene, a single layer of antimony atoms, is a promising 2D material with potential applications in a variety of technological fields, including optoelectronics and energy harvesting. Recently, the isolation of a single layer of antimonene has opened the door to the possibility of realizing these predictions. In this work, recent progresses on antimonene are reviewed.
http://ift.tt/2gGiFj4
Incidence of postpartum anaemia and risk factors associated with vaginal birth
Publication date: Available online 26 October 2017
Source:Women and Birth
Author(s): Ana Rubio-Álvarez, Milagros Molina-Alarcón, Antonio Hernández-Martínez
BackgroundPostpartum anaemia is a frequent and potentially preventable complication that has serious repercussions on health and maternal well-being.AimDetermine the incidence and perinatal risk factors associated with postpartum anaemia in women who gave birth vaginally.MethodsAn observational and analytical retrospective cohort study conducted at the Mancha-Centro Hospital during the 2010–2014 period. Data were collected from 2990 women who gave birth vaginally. The main outcome variable was postpartum anaemia for two cut-off points (haemoglobin (Hb) <11g/dL and <9g/dL at 24-h postpartum). Women with prepartum anaemia (<11g/dL) were excluded. It included a multivariate analysis by multiple linear regression.Findings45% (1341) of women had postpartum levels of Hb <11g/dL, and 7.1% (212) of women had Hb <9g/dL. The most strongly associated risk factors with more severe anaemia (Hb <9g/dL) were episiotomy (OR 3.19. 95%CI: 2.10-4.84), first stage of labour >9h (OR 2.50. 95%CI: 1.58-3.94), primiparity (OR 2.50. 95%CI: 1.61–3.87) and previous caesarean section (OR 2.43. 95%CI: 1.51–3.90). The other independent risk factors for both Hb cut-off points were prolonged second stage of labour, instrumental birth, tearing>first degree, non-practice of active management and heavier birth weight of newborns.ConclusionPostpartum anaemia has a high incidence. The active management of third stage of labour, selective practice of episiotomies, and performing instrumental births only when strictly necessary are efficient measures to lower the incidence of postpartum anaemia.
http://ift.tt/2zacgYI
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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