http://ift.tt/2hDQqVW
Παρασκευή 29 Σεπτεμβρίου 2017
Overt Skeletal Metastases in a Patient of Occult (Microscopic) Follicular Thyroid Carcinoma: a Rare Case
Abstract
Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.
http://ift.tt/2fYjxj0
Using Linkage Maps as a Tool To Determine Patterns of Chromosome Synteny in the Genus Salvelinus
Next generation sequencing techniques have revolutionized the collection of genome and transcriptome data from non-model organisms. This manuscript details the application of restriction site associated DNA sequencing (RADseq) to generate a marker dense genetic map for Brook trout (Salvelinus fontinalis). The consensus map was constructed from three full-sib families totaling 176 F1 individuals. The map consisted of 42 linkage groups with a total female map size of 2502.5 cM, and a total male map size of 1863.8 cM. Synteny was confirmed with Atlantic salmon for 38 linkage groups, with Rainbow trout for 37 linkage groups, Arctic char for 36 linkage groups, and with a previously published Brook trout linkage map for 39 linkage groups. Comparative mapping confirmed the presence of eight metacentric and 34 acrocentric chromosomes in Brook trout. Six metacentric chromosomes seem to be conserved with Arctic char suggesting there have been at least two species specific fusion and fission events within the genus Salvelinus. In addition, the sex marker (sdY; sexually dimorphic on the Y chromosome) was mapped to Brook trout BC35, which is homologous with Atlantic salmon Ssa09qa, Rainbow trout Omy25, and Arctic char AC04q. Ultimately, this linkage map will be a useful resource for studies on the genome organization of Salvelinus, and facilitates comparisons of the Salvelinus genome with Salmo and Oncorhynchus.
http://ift.tt/2yMTp2B
First Draft Genome Sequence of the Pathogenic Fungus Lomentospora prolificans (formerly Scedosporium prolificans)
Here we describe the sequencing and assembly of the pathogenic fungus Lomentospora prolificans using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,627,092 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8,896 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb.
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ASF1A Facilitates DNA Double-Strand Break Repair by NHEJ [Research Watch]
ASF1A promotes NHEJ over homologous recombination for DNA double-strand break (DSB) repair.
http://ift.tt/2fy5Ir3
Tigecycline May Selectively Target Leukemic Stem Cells in CML [Research Watch]
Tigecycline inhibits mitochondrial oxidative phosphorylation to target leukemic stem cells (LSC).
http://ift.tt/2yfegi7
Durvalumab Promising for NSCLC [News in Brief]
Checkpoint inhibitor increases progression-free survival, response rate in patients with stage III non–small cell lung cancer.
http://ift.tt/2fyFxRi
PPARG-Activated Bladder Cancer Cells Exhibit a PPARG Dependency [Research Watch]
PPARG-selective inverse agonists can suppress proliferation in PPARG-activated bladder cancer cells.
http://ift.tt/2yd6vsM
The EGFR-AS1 Long Noncoding RNA Modulates EGFR TKI Sensitivity [Research Watch]
A synonymous EGFR mutation promotes TKI response by reducing EGFR-AS1 levels in squamous-cell cancer.
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Fatty-Acid Catabolism Promotes T-cell Revitalization in Melanoma [Research Watch]
A hypoxic and hypoglycemic tumor microenvironment induces the metabolic reprogramming of CD8+ TILs.
http://ift.tt/2yfdX6X
Somatic super-enhancer duplications and hotspot mutations lead to oncogenicactivation of the KLF5 transcription factor [Research Articles]
The Krüppel-like family of transcription factors (KLF) plays critical roles in human development and is associated with cancer pathogenesis. KLF5 has been shown to promote cancer cell proliferation and tumorigenesis, and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here we show that these alterations activate KLF5 by three distinct mechanisms. 1) Focal amplification of super-enhancers activates KLF5 expression in squamous cell carcinomas. 2) Missense mutations disrupt KLF5-FBXW7 interactions to increase KLF5 protein stability in colorectal cancer. 3) Cancer type-specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with KLF5 overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.
http://ift.tt/2yNbYDO
mTOR and HDAC inhibitors converge on the TXNIP/thioredoxin pathway to cause catastrophic oxidative stress and regression of RAS-driven tumors [Research Articles]
While agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here we identify a promising combination therapy that kills NF1-mutant tumors by triggering catastrophic oxidative stress. Specifically, we show that mTOR and HDAC inhibitors kill aggressive nervous system malignancies and shrink tumors in vivo by converging on the TXNIP/thioredoxin anti-oxidant pathway, through cooperative effects on chromatin and transcription. Accordingly, TXNIP triggers cell death by inhibiting thioredoxin and activating Apoptosis Signal-regulating Kinase 1 (ASK1). Moreover, this drug combination also kills NF1-mutant and KRAS-mutant non-small cell lung cancers. Together these studies identify a promising therapeutic combination for several currently untreatable malignancies, and reveal a protective nodal point of convergence between these important epigenetic and oncogenic enzymes.
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Save the Date! Lone Star Rhinology and Rhinoplasty Course Scheduled for November
http://ift.tt/2yzlGJ2
Dr. Amber Luong Receives 2017 Helen F. Krause, MD Memorial Trailblazer Award
http://ift.tt/2yxTQgc
ORL Frontiers 2017 Recap
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Racial and Ethnic Disparities in Non-alcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75–100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta-analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis.
http://ift.tt/2fY5eLA
Association Between Hepatic Steatosis, Measured by Controlled Attenuation Parameter, and Fibrosis Burden in Chronic Hepatitis B
The interaction between chronic hepatitis B (CHB) and hepatic steatosis is poorly understood. We investigated whether measurement of controlled attenuation parameter (CAP), a non-invasive method to quantify steatosis, can assist in monitoring patients with CHB.
http://ift.tt/2ydzoFl
Fructans Exacerbate Symptoms in a Subset of Children with Irritable Bowel Syndrome
Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive.
http://ift.tt/2fXOu7g
336 A Comparison of Anatomical Landmark vs Ultrasound Static vs Ultrasound Real-Time Technique for Internal Jugular Vein Cannulation
Ultrasound-guided real-time technique (US RT) for internal jugular vein (IJV) access is the gold standard recommendation for IJV cannulation. Ultrasound static technique (US ST) (prelocation of IJV with ultrasound and marking the venipuncture site on the neck and cannulating with guidance skin marking) can also be used to cannulate IJV in most of the patients requiring IJV assess in the emergency department (ED) and Intensive Care Unit (ICU) with equal success rate, reduced complication, better field sterility, better utilization of resources, and with an overall lower cost.
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234 Safety and Efficacy of Intravenous Lidocaine for Pain Management in the Emergency Department: A Systematic Review and Meta-Analysis
This is a systematic review and meta-analysis to evaluate the safety and efficacy of intravenous (IV) lidocaine in adult patients with acute and chronic pain undergoing pain management in the emergency department (ED).
http://ift.tt/2yNl1o7
202 Unexpected Benefits of Emergency Department-Based Social Support Intervention for Patients With Diabetes
Diabetes and its complications result in over 2 million ED visits annually in the United States. This burden on patients, communities and the health care system is particularly pronounced in safety-net hospitals. Both social support-based and mobile health (mHealth)-based interventions have improved glycemic control and health behaviors while reducing ED visits among vulnerable populations. We designed a project combining the two modalities, delivering text messages to social supporters of ED patients with diabetes.
http://ift.tt/2wo7Vft
396 Ultrasound-Guided Resuscitation of Critically Ill Patients Presenting to the Emergency Department in a Resource-Limited Setting
To examine the impact of cardiopulmonary ultrasonography (CPUS) on diagnostic accuracy and early clinical care of critically ill patients presenting to the emergency department (ED) at the Komfo Anokye Teaching Hospital in Kumasi, Ghana.
http://ift.tt/2wpwxoh
230 The Willingness of Adolescents to Commit to Safe Use, Storage, and Disposal of Prescription Opiates in the Emergency Department
Monitoring the Future report shows that almost 1 out of 10 children has misused a narcotic by 12th grade. Importantly, the leading diversion source is leftover pills from their own previous prescriptions – the majority of which originate in the emergency department. Although decreasing prescriptions has been the primary focus of ED-based interventions and policies, in April 2017 the American Medical Association Task Force to Reduce Opioid Abuse released new official recommendations promoting safe use, storage and disposal of prescription opioids after a prescription is written.
http://ift.tt/2yOiB94
222 The Pediatric Blast Injury: Out-of-Hospital and Emergency Department Resuscitation and Resource Utilization in Iraq and Afghanistan
Pediatric trauma care is a significant challenge in the deployed setting in accordance with medical rules of engagement. Traumatic injuries due to explosives are largely unique to the combat-zone setting. Thus, little data exist specific to care of the pediatric patient with trauma due to explosion. We describe the out-of-hospital and emergency department (ED) care of the pediatric explosive injury.
http://ift.tt/2woNKy8
206 Safety of Single- vs Two-physician Procedural Sedation in a Small Community Emergency Department
Sedation is commonly required for painful procedures in the emergency department (ED). Many hospital have policies that mandate two physicians participate in deep sedation cases. Evidence is lacking, however, that a two-physician approach improves safety outcomes. We compared the safety of ED procedural sedation between a two-physician and a single-physician policy in a small, single-coverage community ED.
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348 Trends in the Reports of Naloxone as Reported to a Regional US Poison Center
The U.S. Department of Health and Human Services recommends expanding naloxone access as a priority area as the opioid crisis worsens. The objective of this study is to evaluate the trends and describe the demographic and clinical characteristics of calls from the emergency department (ED) to a regional poison center (PC), where naloxone was being recommended or utilized as therapy as well as determine the role of the PCs in making the initial decision on naloxone administration.
http://ift.tt/2yOiomi
340 Accuracy of Point-of-Care Ultrasound for the Diagnosis of Scrotal Pathology in the Emergency Department
Acute scrotal pain is a common emergency department complaint. Ultrasound has been shown to be an accurate and rapid method of ruling out surgical emergencies of the scrotum. Previous reports of scrotal ultrasound by emergency physicians have focused on individual cases; and to date, no large-scale report of the variety of presentations is available. The objective of our study is to determine the diagnostic accuracy of emergency physician performed point-of care scrotal ultrasound for detecting scrotal pathology in the emergency department.
http://ift.tt/2wpwwRf
Intraoperative 5-aminolevulinic acid-induced photodynamic diagnosis of metastatic brain tumors with histopathological analysis
Abstract
Background
Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors.
Methods
We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue.
Results
Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2–6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2–3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P = 0.004).
Conclusion
Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection.
Trial registration
Institutional Review Board of Osaka Medical College No. 42, registered February 17, 1998, and No. 300, registered April 1, 2008. They were retrospectively registered.
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Regional Variation in Neonatal Intensive Care Admissions and the Relationship to Bed Supply
To characterize geographic variation in neonatal intensive care unit (NICU) admission rates across the entire birth cohort and evaluate the relationship between regional bed supply and NICU admission rates.
http://ift.tt/2xMvmT6
Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial
To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables.
http://ift.tt/2xMc5B3
Return and Disclosure of Research Results: Parental Attitudes and Needs Over Time in Pediatric Oncology
To explore parental attitudes regarding the return and disclosure of research findings in pediatric cancer trials over time.
http://ift.tt/2fxwTSW
Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial
To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic.
http://ift.tt/2fygu0F
Group Living and Male Dispersal Predict the Core Gut Microbiome in Wild Baboons
Abstract
The mammalian gut microbiome plays a profound role in the physiology, metabolism, and overall health of its host. However, biologists have only a nascent understanding of the forces that drive inter-individual heterogeneity in gut microbial composition, especially the role of host social environment. Here we used 178 samples from 78 wild yellow baboons (Papio cynocephalus) living in two social groups to test how host social context, including group living, social interactions within groups, and transfer between social groups (e.g., dispersal) predict inter-individual variation in gut microbial alpha and beta diversity. We also tested whether social effects differed for prevalent "core" gut microbial taxa, which are thought to provide primary functions to hosts, versus rare "non-core" microbes, which may represent relatively transient environmental acquisitions. Confirming prior studies, we found that each social group harbored a distinct gut microbial community. These differences included both non-core and core gut microbial taxa, suggesting that these effects are not solely driven by recent gut microbial exposures. Within social groups, close grooming partners had more similar core microbiomes, but not non-core microbiomes, than individuals who rarely groomed each other, even controlling for kinship and diet similarity between grooming partners. Finally, in support of the idea that the gut microbiome can be altered by current social context, we found that the longer an immigrant male had lived in a given social group, the more closely his gut microbiome resembled the gut microbiomes of the group's long-term residents. Together, these results reveal the importance of a host's social context in shaping the gut microbiome and shed new light onto the microbiome-related consequences of male dispersal.http://ift.tt/2x3wEVX
Neurobiology of Female Mate Choice in Frogs: Auditory Filtering and Valuation
Abstract
Mate choice is a decision making process with profound implication for the reproductive success of both the sender and the chooser. Preferences for conspecific over heterospecific males and for some conspecifics over others are typically mediated by a female's response to signals produced by males. And although one can experimentally describe a female's preference function, there is relatively little understood about the neural mechanisms mediating these preferences. In anurans, mating preferences have often been explained in terms of sensory biases. Indeed, in the túngara frog (Physalaemus pustulosus), the auditory system appears to act as a filter for conspecific calls. However, auditory responses are not good predictors of intraspecific mating preferences in túngara frogs. Rather, neural activity in the preoptic area, which can be gated by estradiol, is a better predictor of mating preferences. A similar pattern holds in spadefoot toads (Spea bombifrons): the preoptic area, but not the auditory midbrain, integrates physiological cues in its response to mating calls in a pattern that predicts preferences. Neuroanatomically, the anuran preoptic area is poised to mediate forebrain influences on auditory response of the midbrain and it has descending projections to the medulla and spinal cord that could directly influence motor responses. Indeed, lesions of the preoptic area abolish phonotaxis. A role for the preoptic area in mating preferences is supported by studies in mammals that show the preoptic area is required for the expression of preferences. Further, activity of the preoptic area correlates with mating preference in fish. This leads to a model for the neurobiological mechanisms of mate choice, in which sensory systems filter relevant signals from irrelevant ones, but the preoptic area assigns value to the range of relevant signals.http://ift.tt/2xPD1QG
A Geospatial Epidemiologic Analysis of Nontuberculous Mycobacterial Infection: An Ecological Study in Colorado
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1523-1532, October 2017.
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Hypersensitivity Pneumonitis: Lessons from the Great Imitator in Interstitial Lung Disease
http://ift.tt/2fx5Zug
Derivation and Validation of a Prognostic Model to Predict 6-Month Mortality in an Intensive Care Unit Population
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1556-1561, October 2017.
http://ift.tt/2fzg4a1
Reply: Tidal Carbon Dioxide as a Prognostic Feature in Inoperable Chronic Thromboembolic Pulmonary Hypertension
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1604-1605, October 2017.
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Prognostication during Critical Illness: Moving the Field Forward
http://ift.tt/2fzg2yV
Rationale and Design of the Lung Cancer Screening Implementation. Evaluation of Patient-Centered Care Study
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1581-1590, October 2017.
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Acute Dyspnea in a Woman with Lupus: Rapid Assessment Using Point-of-Care Ultrasound Imaging
http://ift.tt/2hD9gMU
Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1548-1555, October 2017.
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Comorbidity Profiles and Their Effect on Treatment Selection and Survival among Patients with Lung Cancer
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1571-1580, October 2017.
http://ift.tt/2fy3gAX
The Limits of Pattern Recognition: Nodular Lung Disease in a Syrian Refugee
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Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography Predicts Survival in Chronic Hypersensitivity Pneumonitis
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1533-1538, October 2017.
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Decisions around Long-term Ventilation for Children. Perspectives of Directors of Pediatric Home Ventilation Programs
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1539-1547, October 2017.
http://ift.tt/2fxWyLc
Skeletal Muscle Ultrasound in Critical Care: A Tool in Need of Translation
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1495-1503, October 2017.
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Pulmonary Hypertension and Primary Graft Dysfunction in Lung Transplant Recipients: We Still Have a Long Way to Go
http://ift.tt/2fxoxKT
A Challenging Diagnosis of Endobronchial Aortic Pseudoaneurysm
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Dry Powder Inhalers and Humidity: Another Factor to Consider to Ensure Adequate Lung Delivery
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1602-1602, October 2017.
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Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension
Annals of the American Thoracic Society, Volume 14, Issue 10, Page 1514-1522, October 2017.
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Comorbidity Profiles of Patients with Lung Cancer: A New Approach to Risk Stratification?
http://ift.tt/2hBTNgc
Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine
Abstract
Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core—and highly addictive—constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of "harm," their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017. © 2017 American Cancer Society, Inc.
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Treatment of renal cell carcinoma: Current status and future directions
Abstract
Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents—including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor—have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017. © 2017 American Cancer Society.
http://ift.tt/2woZzED
Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material
Here, we present a protocol to describe a simple, fast and efficient prion amplification technique, the real-time quaking-induced conversion (RT-QuIC) method.
http://ift.tt/2xEncNb
Erratum
An error appeared in the 15 June 2017 issue of the journal [Marks SM, Mase SR, Morris SB. Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis. Clin Infect Dis 2017; 64(12):1670–77. doi:10.1093/cid/cix208]. FQ/ETA was not cost-effective, was dominated by other regimens, in all scenarios examined. This results in the following changes:
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http://ift.tt/2yyhObh
Erratum
An error appeared in the 1 September 2016 issue of the journal [Kalil AC, Mertersky M, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111]. In Table 4, the targeted level of vancomycin should be "15–20 µg/mL trough level" [not "15–20 mg/ml"].
http://ift.tt/2fW2KNI
http://ift.tt/2fW2KNI
Keeping Up With a World in Motion: Screening Strategies for Migrating Populations
tuberculosistuberculosis screeningmigrationasylum seekersmigrants
http://ift.tt/2fXc8R1
http://ift.tt/2fXc8R1
Systematic Tuberculosis Screening in Asylum Seekers in Italy
Abstract
The preliminary findings of a tuberculosis (TB) screening of asylum seekers performed in a reception center located in northern Italy reveal a post-entry screening prevalence rate of 535 per 100000 individuals screened. This result shows that systematic use of chest radiography is a useful tool for active TB screening among asylum seekers in Italy.http://ift.tt/2yxP0zq
Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar
Abstract
Background
Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure. Methods
Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2–59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens. Results
At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34–100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children. Conclusions
Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.http://ift.tt/2fXg2JO
Erratum
A system error occurred in the 15 May 2017 and 1 June 2017 issues of the journal. A test script was triggered by the typesetter at press time, corrupting some parenthetical data within some articles. Single letters, numerals, or symbols were replaced with the issue's volume and number. The affected articles are listed below, in the order they appear within the issues.
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Reply to Dobler
To the Editor—We thank Dr Dobler for her comments regarding the methods of how we calculated and compared cumulative incidence of tuberculosis (TB) in cancer patients and country-specific TB incidence in our study [1]. We estimated the cumulative incidence (proportion) of developing TB during a specific study period in cancer cohorts divided by the mean annual TB incidence in the general US population over the same study period. We were not able to estimate the incidence of TB per year or by unit of time of follow-up in cancer patients because neither time to TB diagnosis of all cases nor the amount of time cancer cohorts were followed was reported in the included studies. Although we adjusted for the change in TB incidence in the general population over the study period, we assumed that the majority of TB cases would have occurred early after the cancer diagnosis. We did not account for the fact that the denominator estimated the annual TB incidence in the United States (also a proportion) and thus all new cases occurring in the US population per year. On reexamination of the data, 2 of the included studies provide insight into the timing of onset of active TB after a cancer diagnosis and support our assumption [2, 3]. In the study by Kaplan et al, 41% of TB cases occurred concurrently with the cancer diagnosis and 90% of all cases occurred within 18 months of cancer therapy [2]. Similarly, in the study by Libshitz et al, 30% of TB cases were diagnosed concurrently with the cancer and 79% of all cases occurred within 18 months of completion of cancer therapy, which for most cancers is approximately 2 years after cancer diagnosis [3]. Extrapolating from studies in which follow-up time of cancer cohorts was reported (Table 1 of our manuscript), this was usually relatively short (2–5 years) whereas study periods were generally longer (up to 13 years) [1]. Thus, cancer patients in the Kamboj study were likely not followed for the entire 25-year study period and, if the timing of TB after cancer diagnosis followed the same pattern as the Kaplan and Libshitz studies, the majority of TB cases also would have occurred within 2 years of cancer diagnosis [2–4].
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http://ift.tt/2yy6ETR
Cumulative Incidence and Incidence Rate Ratio for Estimation of Risk of Tuberculosis in Patients With Cancer
To the Editor—In their systematic review and meta-analysis of the risk of active tuberculosis (TB) in patients with cancer, Cheng et al evaluated the cumulative incidence of TB among patients with cancer and used this information together with annual country-specific TB incidence rates from the World Health Organization to estimate the incidence rate ratio of TB in patients with cancer compared to the general population [1]. The analysis raises some methodological concerns that have implications for the interpretation of the results. The authors use the term "cumulative incidence rate," when indeed cumulative incidence is a proportion, not a rate (events expressed per unit time) [2, 3]. For included studies that only contained information on cumulative incidence, but not an actual incidence rate, the authors used cumulative incidence (over the study period) divided by the incidence rate per year in the general population to calculate an incidence rate ratio. This calculation is methodologically incorrect [3] and will result in overestimation of the incidence rate ratio. The included study by Kamboj and Sepkowitz that evaluated the risk of TB among patients with cancer at the Memorial Sloan-Kettering Cancer Center in New York City between 1980 and 2004 illustrates the problem [4]. In this study, there were 103 cases of TB among 186843 patients with cancer during the study period, resulting in a cumulative incidence of 55 cases of TB per 100000 patients (over 25 years). In Table 1 of their article, Cheng et al presented the cumulative incidence of 55 and divided this number by the TB incidence per 100000 persons/year in the general population during the study period (8.6/100000/year), resulting in an incidence rate ratio (calculated by the authors) of 6.3 (55/8.6). The problem is that the cumulative incidence among cancer patients accumulated over 25 years whereas the incidence in the general population represented events occurring within 1 year. Assuming a regular distribution of these TB cases over time, the TB incidence rate would have been 2.2/100000 per year (55 cases of TB per 100000 patients over 25 years), but of course this estimate is not correct either, because it wrongly assumes that every patient survived and was followed up for 25 years. Thus, the available study data do not allow calculation of an incidence rate ratio, and the analysis should have been limited to studies that provided a true incidence rate of TB.
http://ift.tt/2fXfPq0
http://ift.tt/2fXfPq0
Fluoroquinolone Resistance Mutation Detection Is Equivalent to Culture-Based Drug Sensitivity Testing for Predicting Multidrug-Resistant Tuberculosis Treatment Outcome: A Retrospective Cohort Study
Abstract
Background
Molecular diagnostics that rapidly and accurately predict fluoroquinolone (FQ) resistance promise to improve treatment outcomes for individuals with multidrug-resistant (MDR) tuberculosis (TB). Mutations in the gyr genes, though, can cause variable levels of in vitro FQ resistance, and some in vitro resistance remains unexplained by gyr mutations alone, but the implications of these discrepancies for treatment outcome are unknown. Methods
We performed a retrospective cohort study of 172 subjects with MDR/extensively drug-resistant TB subjects and sequenced the full gyrA and gyrB open reading frames in their respective sputum TB isolates. The gyr mutations were classified into 2 categories: a set of mutations that encode high-level FQ resistance and a second set that encodes intermediate resistance levels. We constructed a Cox proportional model to assess the effect of the gyr mutation type on the time to death or treatment failure and compared this with in vitro FQ resistance, controlling for host and treatment factors. Results
Controlling for other host and treatment factors and compared with patients with isolates without gyr resistance mutations, "high-level" gyr mutations significantly predict poor treatment outcomes with a hazard ratio of 2.6 (1.2–5.6). We observed a hazard of death and treatment failure with "intermediate-level" gyr mutations of 1.3 (0.6–3.1), which did not reach statistical significance. The gyr mutations were not different than culture-based FQ drug susceptibility testing in predicting the hazard of death or treatment failure and may be superior. Conclusions
FQ molecular-based diagnostic tests may better predict treatment response than traditional drug susceptibility testing and open avenues for personalizing TB therapy.http://ift.tt/2fXfKCI
Characterization of Aerosols Generated During Patient Care Activities
Abstract
Background
Questions remain about the degree to which aerosols are generated during routine patient care activities and whether such aerosols could transmit viable pathogens to healthcare personnel (HCP). The objective of this study was to measure aerosol production during multiple patient care activities and to examine the samples for bacterial pathogens. Methods
Five aerosol characterization instruments were used to measure aerosols during 7 patient care activities: patient bathing, changing bed linens, pouring and flushing liquid waste, bronchoscopy, noninvasive ventilation, and nebulized medication administration (NMA). Each procedure was sampled 5 times. An SKC BioSampler was used for pathogen recovery. Bacterial cultures were performed on the sampling solution. Patients on contact precautions for drug-resistant organisms were selected for most activity sampling. Any patient undergoing bronchoscopy was eligible. Results
Of 35 sampling episodes, only 2 procedures showed a significant increase in particle concentrations over baseline: NMA and bronchoscopy with NMA. Bronchoscopy without NMA and noninvasive ventilation did not generate significant aerosols. Of 78 cultures from the impinger samples, 6 of 28 baseline samples (21.4%) and 14 of 50 procedure samples (28.0%) were positive. Conclusions
In this study, significant aerosol generation was only observed during NMA, both alone and during bronchoscopy. Minimal viable bacteria were recovered, mostly common environmental organisms. Although more research is needed, these data suggest that some of the procedures considered to be aerosol-generating may pose little infection risk to HCP.http://ift.tt/2yy6zzx
A 17-Year Nationwide Study of Burkholderia cepacia Complex Bloodstream Infections Among Patients in the United States Veterans Health Administration
Abstract
Background
Burkholderia cepacia complex (Bcc) are a group of multidrug-resistant gram-negative bacteria rarely reported in patients without cystic fibrosis (CF) or immunocompromising conditions. We investigated Bcc bloodstream infections (BSIs) in a cohort of non-CF patients from the US Veterans Health Administration (VHA). Methods
Using VHA databases, we identified patients with Bcc BSI at facilities nationwide from 1999 through 2015. We ascertained clinical characteristics, treatments, and outcomes and identified factors associated with 30-day mortality in logistic regression analysis. Results
We identified 248 patients with Bcc BSI, who were of advanced age (mean, 68 years), chronically ill, and had severe disease. The most common sources were central venous catheters (41%) and pneumonia (20%). Most cases were hospital-acquired (155 [62%]) or healthcare-associated (70 [28%]). Mortality at 14, 30, and 90 days was 16%, 25%, and 36%, respectively. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolones were active against 94% and 88% of isolates, respectively. Susceptibility to ceftazidime and meropenem occurred in approximately 70% of the isolates. The most prescribed antibiotics were fluoroquinolones (35%), followed by carbapenems (20%), TMP-SMX (18.5%), and ceftazidime (11%). In regression analysis, age (OR, 1.06 [95% confidence interval {CI}, 1.02–1.10], per added year) and the Pitt bacteremia score (OR, 1.65 [95% CI, 1.44–1.94], per unit increase) were associated with higher 30-day mortality. Conclusions
In this large cohort of BSIs caused by Bcc, cases were mostly hospital-acquired and we observed high mortality, significant resistance to ceftazidime, and limited use of TMP-SMX. These observations add to our understanding of Bcc infection in non-CF patients and highlight the need for interventions to improve their outcome.http://ift.tt/2fXSFzK
Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent Enhancement in Dengue-Primed Zika Virus–Infected Patients
Abstract
Background
The pathogenesis of severe dengue disease involves immune components as biomarkers. The mechanism by which some dengue virus (DENV)–infected individuals progress to severe disease is poorly understood. Most studies on the pathogenesis of severe dengue disease focus on the process of antibody-dependent enhancement (ADE) as a primary risk factor. With the circulation of Zika virus (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to DENV. The influence of such exposure on Zika disease outcomes remains unknown. Methods
We investigated whether patients previously exposed to DENV exhibited higher viremia when exposed to a subsequent, heterologous dengue or Zika infection than those patients not previously exposed to dengue. We measured viral loads and cytokine profile during patients' acute infections. Results
Neither dengue nor Zika viremia was higher in patients with prior DENV infection, although the power to detect such a difference was only adequate in the ZIKV analysis. Of the 10 cytokines measured, only 1 significant difference was detected: Levels of interleukin 1β (IL-1β) were lower in dengue-infected patients who had experienced a previous dengue infection than patients infected with dengue for the first time. However, power to detect differences between groups was low. In Zika-infected patients, levels of IL-1β showed a significant, positive correlation with viral load. Conclusions
No signs of ADE were observed in vivo in patients with acute ZIKV infection who had prior exposure to DENV.http://ift.tt/2fXfrry
Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients
Abstract
Background
There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Methods
Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. Results
At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Conclusion
Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients.http://ift.tt/2yy6pIr
Importance of Carbapenemase Production Detection in Carbapenem-Resistant Enterobacteriaceae: Looking Beyond Epidemiological Purposes
To the Editor—We read with great interest the recent article by Tamma et al [1], who reported that patients with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) have 2.6 and 4.9 higher odds for bacteremia recurrence at 30 days and mortality at 14 days, respectively, compared with patients with non-CP CRE.
http://ift.tt/2fXQvjV
http://ift.tt/2fXQvjV
High-Dose Daptomycin and Mortality: The Case Is Not Yet Closed
To the Editor—In the 1 March 2017 issue of Clinical Infectious Diseases, Britt et al [1] reported on a cohort study of hospitalized Veterans Affairs (VA) patients treated with standard-, medium-, or high-dose daptomycin (6, 8, or ≥10 mg/kg total body weight, respectively) for vancomycin-resistant Enterococcus bloodstream infection. Although the authors conclude that high-dose daptomycin was associated with improved survival and microbiologic clearance in patients with such infection, we do not believe their data can be interpreted without additional information beyond what was presented in the article.
http://ift.tt/2yy6dcb
http://ift.tt/2yy6dcb
Kids First Pediatric Research Program Moves Forward
Progress continues to be made with the Gabriella Miller Kids First Research Program, which is creating opportunities for investigators from different research communities to share resources and collaborate on research into childhood cancers and certain birth defects.
http://ift.tt/2xRH1At
Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture
Here we describe a facile preparation of chitosan-based injectable hydrogels using dynamic imine chemistry. Methods to adjust the hydrogel's mechanical strength and its application in 3D cell culture are presented.
http://ift.tt/2xDHWok
New Research From Psychological Science
Read about the latest research published in Psychological Science:
Daniel S. Lumian and Kateri McRae
In a 2008 study published in Psychological Science, Cunningham, Van Bavel, and Johnsen found that the amygdala flexibly processes motivationally relevant evaluative information in accordance with current processing goals. Lumian and McRae conducted a preregistered replication of this study following, as closely as possible, the methods of the original study. Twenty-four participants rated the names of famous individuals in three different conditions while being scanned in an fMRI: In the overall-attitude condition, participants considered both positive and negative associations they had for each name before rating it; in the positive condition, participants were asked to focus on positive associations and ignore negative ones; and in the negative condition, participants were asked to focus on negative associations and ignore positive associations. After completing the fMRI portions, participants were asked to indicate whether they recognized each name and to rate each name for positivity, negativity, and emotionality. The authors replicated the results of the original study, adding evidence to the position that cognitive framing can alter whether the amygdala indexes positivity or negativity.
Genomic Imprinting Is Implicated in the Psychology of Music
Samuel A. Mehr, Jennifer Kotler, Rhea M. Howard, David Haig, and Max M. Krasnow
Theories of gene imprinting suggest that maternal genes are expressed in ways that minimize demands for maternal investment, whereas paternal genes are expressed in ways that maximize demands for maternal investment. In Prader-Willi syndrome (PWS), the paternally inherited genes from chromosome 15q11-q13 are unexpressed. Theories of gene imprinting suggest that this type of gene expression should result in an exaggeration of traits that reduce maternal investment. Child-directed song has been proposed to be an indication of maternal attentional investment; consequently, those with PWS may respond to such stimuli in a nontypical way. To study whether PWS is associated with a distinctive musical phenotype, the researchers examined the psychological (heart rate) and behavioral (movement) responses of adults and children with and without PWS to singing. Participants were also assessed for pitch-discrimination ability. Compared with typically developing adults, participants with PWS moved more and had greater reductions in heart rate in response to music, and they had worse pitch-discrimination ability. These results suggest that those with PWS do have a distinctive response to music, characterized by a greater responsivity than their typically developing counterparts
Andrey Chetverikov, Gianluca Campana, and Árni Kristjánsson
Research examining how color is represented in the brain often focuses on people's perception of uniformly colored patches or their perception of only a few colors. Less research has examined how the visual system represents color ensembles. Participants completed an "odd-one-out" visual search, in which they viewed a grid-like arrangement of 36 diamonds, each with one corner cut off. Participants were instructed to find the diamond with a hue least like the others and indicate which corner of that diamond had been removed. The colors of distractor shapes in the display were taken from uniform or Gaussian color distributions. On learning trials, distractor colors were randomly drawn from a specific color distribution range. On test trials, the target color was of various distances from the mean color of the distractors in the previous trial. Analysis of participants' performance on this task indicated a similarity between the physical distribution of colors in the display and their internal representations. This suggests that color ensembles are represented in a more complex way than previously thought and that coding takes into account the mean, the variance, and the shape of the distribution of colors in the environment.
http://ift.tt/2xMq1ep
A Brake for B Cell Proliferation
B cell activation is accompanied by metabolic adaptations to meet the increased energetic demands of proliferation. The metabolic composition of the microenvironment is known to change during a germinal center response, in inflamed tissue and to vary significantly between different organs. To sustain cellular homeostasis B cells need to be able to dynamically adapt to changes in their environment. An inability to take up and process available nutrients can result in impaired B cell growth and a diminished humoral immune response. Furthermore, the metabolic microenvironment can affect B cell signaling and provide a means to avoid aberrant proliferation or modulate B cell function. Thus, a better understanding of the intricate interplay between cell signaling and metabolism could provide novel insight into how B cell function is regulated and have implications for the development of vaccines or treatment of autoimmune disorders and B cell derived malignancies.
Throughout their lifespan, B cells are exposed to different metabolic environments. Signaling pathways regulating cellular responses to metabolic stress not only help to maintain B cell viability and to facilitate cellular functions but may also play an important role in preventing excessive proliferation and malignant transformation.
http://ift.tt/2x2K04E
Solid-State Explosive Reaction for Nanoporous Bulk Thermoelectric Materials
Abstract
High-performance thermoelectric materials require ultralow lattice thermal conductivity typically through either shortening the phonon mean free path or reducing the specific heat. Beyond these two approaches, a new unique, simple, yet ultrafast solid-state explosive reaction is proposed to fabricate nanoporous bulk thermoelectric materials with well-controlled pore sizes and distributions to suppress thermal conductivity. By investigating a wide variety of functional materials, general criteria for solid-state explosive reactions are built upon both thermodynamics and kinetics, and then successfully used to tailor material's microstructures and porosity. A drastic decrease in lattice thermal conductivity down below the minimum value of the fully densified materials and enhancement in thermoelectric figure of merit are achieved in porous bulk materials. This work demonstrates that controlling materials' porosity is a very effective strategy and is easy to be combined with other approaches for optimizing thermoelectric performance.
Nanoporous bulk thermoelectric materials with well-controlled porous structures are fabricated by a unique, ultrafast, yet effective strategy. The lattice thermal conductivity is drastically decreased below the κmin of the fully densified material because of the simultaneously reduction in specific heat, sound speed, and phonon mean free path, leading to much enhanced thermoelectric performance.
http://ift.tt/2x1fMEa
Recent Advances in Alternating Current-Driven Organic Light-Emitting Devices
Abstract
Organic light-emitting devices (OLEDs), typically operated with constant-voltage or direct-current (DC) power sources, are candidates for next-generation solid-state lighting and displays, as they are light, thin, inexpensive, and flexible. However, researchers have focused mainly on the device itself (e.g., development of novel materials, design of the device structure, and optical outcoupling engineering), and little attention has been paid to the driving mode. Recently, an alternative concept to DC-driven OLEDs by directly driving devices using time-dependent voltages or alternating current (AC) has been explored. Here, the effects of different device structures of AC-driven OLEDs, for example, double-insulation, single-insulation, double-injection, and tandem structure, on the device performance are systematically investigated. The formation of excitons and the dielectric layer, which are important to achieve high-performance AC-driven OLEDs, are carefully considered. The importance of gaining further understanding of the fundamental properties of AC-driven OLEDs is then discussed, especially as they relate to device physics.
Recent advances in alternating current (AC)-driven organic light-emitting devices (OLEDs) are highlighted, regarding device structure, operation, and performance, focusing mainly on different device structures of AC-driven OLEDs. These structures include double-insulation, single-insulation, double-injection, and tandem structures. A great future can be expected for high-performance AC-driven OLEDs in further exploration of new device structures, designing new materials, and understanding the device physics.
http://ift.tt/2k9rIxy
A Nanoporous Cytochrome c Film with Highly Ordered Porous Structure for Sensing of Toxic Vapors
Abstract
Creating well-ordered nanoporosity in biomolecules promises stability and activity, offering access to an even wider range of application possibilities. Here, the preparation of nanoporous protein films containing cytochrome c protein molecules is reported through a soft-templating strategy using polystyrene (PS) spheres of different sizes as templates. The stability of the cytochrome c film is demonstrated through electrochemistry studies to show a reusable nature of these films over a long period of time. The size of the PS spheres is varied to tune the pore diameter and the thickness of the cytochrome c films, which are quite stable and highly selective for sensing toxic acidic vapors. The fusion of the templating strategy and the self-assembly of biomolecules may offer various possibilities by generating a new series of porous biomolecules including enzymes with different molecular weights and diameters, peptides, antibodies, and DNA with interesting catalytic, adsorption, sensing, and electronic properties.
Highly ordered nanoporous protein films containing cytochrome c molecules are prepared through the soft-templating strategy, displaying superior stability and selective sensing for toxic organic acid vapors. Quartz-crystal microbalance (QCM) characterization for the nanoporous film with a pore size of 200 nm exhibits a highly selective sensing for toxic acidic vapors.
http://ift.tt/2fwSydY
Virus-Mimicking Chimaeric Polymersomes Boost Targeted Cancer siRNA Therapy In Vivo
Abstract
Small interfering RNA (siRNA) offers a highly selective and effective pharmaceutical for various life-threatening diseases, including cancers. The clinical translation of siRNA is, however, challenged by its short plasma life, poor cell uptake, and cumbersome intracellular trafficking. Here, cNGQGEQc peptide-functionalized reversibly crosslinked chimaeric polymersomes (cNGQ/RCCPs) is shown to mediate high-efficiency targeted delivery of Polo-like kinase1 specific siRNA (siPLK1) to orthotopic human lung cancer in nude mice. Strikingly, siRNA is completely and tightly loaded into the aqueous lumen of the polymersomes at an unprecedentedly low N/P ratio of 0.45. cNGQ/RCCPs loaded with firefly luciferase specific siRNA (siGL3) or siPLK1 are efficiently taken up by α3β1-integrin-overexpressing A549 lung cancer cells and quickly release the payloads to the cytoplasm, inducing highly potent and sequence-specific gene silencing in vitro. The in vivo studies using nude mice bearing orthotopic A549 human lung tumors reveal that siPLK1-loaded cNGQ/RCCPs boost long circulation, superb tumor accumulation and selectivity, effective suppression of tumor growth, and significantly improved survival time. These virus-mimicking chimaeric polymersomes provide a robust and potent platform for targeted cancer siRNA therapy.
α3β1-Integrin-specific reversibly crosslinked chimaeric polymersomes show highly efficient loading and targeted delivery of Polo-like kinase1 specific small interfering RNA to orthotopic A549 human lung tumors in nude mice, leading to potent tumor suppression, effective inhibition of metastasis, and markedly improved survival rate.
http://ift.tt/2hCwrXX
Direct Observation of Halide Migration and its Effect on the Photoluminescence of Methylammonium Lead Bromide Perovskite Single Crystals
Abstract
Optoelectronic devices based on hybrid perovskites have demonstrated outstanding performance within a few years of intense study. However, commercialization of these devices requires barriers to their development to be overcome, such as their chemical instability under operating conditions. To investigate this instability and its consequences, the electric field applied to single crystals of methylammonium lead bromide (CH3NH3PbBr3) is varied, and changes are mapped in both their elemental composition and photoluminescence. Synchrotron-based nanoprobe X-ray fluorescence (nano-XRF) with 250 nm resolution reveals quasi-reversible field-assisted halide migration, with corresponding changes in photoluminescence. It is observed that higher local bromide concentration is correlated to superior optoelectronic performance in CH3NH3PbBr3. A lower limit on the electromigration rate is calculated from these experiments and the motion is interpreted as vacancy-mediated migration based on nudged elastic band density functional theory (DFT) simulations. The XRF mapping data provide direct evidence of field-assisted ionic migration in a model hybrid-perovskite thin single crystal, while the link with photoluminescence proves that the halide stoichiometry plays a key role in the optoelectronic properties of the perovskite.
Bromide-ion migration is directly observed in a methylammonium lead bromide perovskite single crystal under bias using a synchrotron-based X-ray fluorescence nanoprobe. Photoluminescence mapping indicates that bromide-rich regions exhibit enhanced photoluminescence. The close correspondence between the local bromide concentration and photoluminescence in response to bias reveals the importance of non-stoichiometry in determining optoelectronic performance in halide perovskites.
http://ift.tt/2xLwPc9
Improved Domain Size and Purity Enables Efficient All-Small-Molecule Ternary Solar Cells
Abstract
An all-small-molecule ternary solar cell is achieved with a power conversion efficiency of 10.48% by incorporating phenyl-C71-butyric-acid-methyl ester (PC71BM) into a nonfullerene binary system. The addition of PC71BM is found to modulate the film morphology by improving the domain purity and decreasing the domain size. This modulation facilitates charge generation and suppresses charge recombination, as manifested by the significantly enhanced short-circuit current density and fill factor. The results correlate the domain characteristics with the device performance and offer new insight from the perspective of morphology modulation for constructing efficient ternary devices.
An all-small-molecule ternary solar cell is achieved with a power conversion efficiency of 10.48% by incorporating the phenyl-C71-butyric-acid-methyl ester (PC71BM) into a nonfullerene small-molecule binary system. The addition of PC71BM is found to modulate the film morphology by improving the domain purity and decreasing the domain size. This facilitates charge generation and suppresses charge recombination.
http://ift.tt/2fwReb0
Ultrafast Magnetization Manipulation Using Single Femtosecond Light and Hot-Electron Pulses
Abstract
Current-induced magnetization manipulation is a key issue for spintronic applications. This manipulation must be fast, deterministic, and nondestructive in order to function in device applications. Therefore, single- electronic-pulse-driven deterministic switching of the magnetization on the picosecond timescale represents a major step toward future developments of ultrafast spintronic systems. Here, the ultrafast magnetization dynamics in engineered Gdx[FeCo]1−x-based structures are studied to compare the effect of femtosecond laser and hot-electron pulses. It is demonstrated that a single femtosecond hot-electron pulse causes deterministic magnetization reversal in either Gd-rich and FeCo-rich alloys similarly to a femtosecond laser pulse. In addition, it is shown that the limiting factor of such manipulation for perpendicular magnetized films arises from the formation of a multidomain state due to dipolar interactions. By performing time-resolved measurements under various magnetic fields, it is demonstrated that the same magnetization dynamics are observed for both light and hot-electron excitation, and that the full magnetization reversal takes place within 40 ps. The efficiency of the ultrafast current-induced magnetization manipulation is enhanced due to the ballistic transport of hot electrons before reaching the GdFeCo magnetic layer.
Deterministic switching of magnetization without any external magnetic field is demonstrated using single femtosecond hot-electron or laser pulses in an engineered GdxFeCo1−x-based structure. It is found that a hot-electron pulse allows a reversed magnetic state within 40 ps in either Gd-rich or FeCo-rich alloys, similar to a femtosecond laser pulse. This study paves the way for ultrafast spintronics.
http://ift.tt/2xLb2Bd
Cerium and Ytterbium Codoped Halide Perovskite Quantum Dots: A Novel and Efficient Downconverter for Improving the Performance of Silicon Solar Cells
Abstract
Quantum cutting can realize the emission of multiple near-infrared photons for each ultraviolet/visible photon absorbed, and has potential to significantly improve the photoelectric conversion efficiency (PCE) of solar cells. However, due to the lack of an ideal downconversion material, it has merely served as a principle in the laboratory until now. Here, the fabrication of a novel type of quantum cutting material, CsPbCl1.5Br1.5:Yb3+, Ce3+ nanocrystals is presented. Benefiting from the larger absorption cross-section, weaker electron–phonon coupling, and higher inner luminescent quantum yield (146%), the doped perovskite nanocrystals are successfully explored as a downconverter of commercial silicon solar cells (SSCs). Noticeably, the PCE of the SSCs is improved from 18.1% to 21.5%, with a relative enhancement of 18.8%. This work exhibits a cheap, convenient, and effective way to enhance the PCE of SSCs, which may be commercially popularized in the future.
Cerium and ytterbium codoped halide perovskite quantum dots display an efficient near-infrared emission with inner luminescent quantum yield of 146%. The quantum dots are explored to enhance the performance of silicon solar cells with a relative enhancement of 18.8%.
http://ift.tt/2fwqDed
Recent Advances in the Generation of Antibody–Nanomaterial Conjugates
Abstract
Targeted nanomedicines have significantly changed the way new therapeutics are designed to treat disease. Central to successful therapeutics is the ability to control the dynamics of protein–nanomaterial interactions to enhance the therapeutic effect of the nanomedicine. The aim of this review is to illustrate the diversity and versatility of the conjugation approaches involved in the synthesis of antibody–nanoparticle conjugates, and highlight significant new advances in the field of bioconjugation. Such nanomedicines have found utility as both advanced therapeutic agents, as well as more complex imaging contrast agents that can provide both anatomical and functional information of diseased tissue. While such conjugates show significant promise as next generation targeted nanomedicines, it is recognized that there are in fact no clinically approved targeted therapeutics on the market. This fact is reflected upon within this review, and attempts are made to draw some reasoning from the complexities associated with the bioconjugation chemistry approaches that are typically utilized. Present trends, as well as future directions of next generation targeted nanomedicines are also discussed.
Antibody–nanoparticle conjugates are employed as advanced therapeutic agents. In this review, the different strategies used in the production of antibody-conjugated nanoparticles are highlighted with the intention of providing the reader with a synopsis of current and emerging trends in the field. In particular, attempts are made to draw some reasoning from the complexities associated with the existing bioconjugation approaches.
http://ift.tt/2xDgUNN
Droplet-Templated Antisolvent Spherical Crystallization of Hydrophilic and Hydrophobic Drugs with an in situ Formed Binder
Abstract
This study presents a novel droplet-templated antisolvent spherical crystallization method applicable to both hydrophilic and hydrophobic drugs. In both cases, an alginate hydrogel binder forms in situ, concurrently with the crystallization process, effectively binding the drug crystals into monodisperse spheres. This study presents a detailed process description with mass transfer modeling, and with characterization of the obtained alginate/drug spheres in terms of morphology, composition, and drug loading. Although glycine and carbamazepine are used as model hydrophilic and hydrophobic drugs, this method is easily generalized to other drugs, and offers several benefits such as minimal thermal impact, fast crystallization rates, high drug–binder loading ratios, and high selectivity toward metastable polymorphs.
This paper presents a novel antisolvent crystallization method for both hydrophilic and hydrophobic drugs using droplets as templates and alginate hydrogel as an in situ binder. The simultaneous crystallization and gelation processes effectively encapsulate the precipitated crystals of different sizes into highly monodisperse spherical particles to facilitate the downstream formulation processes in pharmaceutical manufacturing.
http://ift.tt/2kcLbOb
Droplet Microarray Based on Patterned Superhydrophobic Surfaces Prevents Stem Cell Differentiation and Enables High-Throughput Stem Cell Screening
Abstract
Over the past decades, stem cells have attracted growing interest in fundamental biological and biomedical research as well as in regenerative medicine, due to their unique ability to self-renew and differentiate into various cell types. Long-term maintenance of the self-renewal ability and inhibition of spontaneous differentiation, however, still remain challenging and are not fully understood. Uncontrolled spontaneous differentiation of stem cells makes high-throughput screening of stem cells also difficult. This further hinders investigation of the underlying mechanisms of stem cell differentiation and the factors that might affect it. In this work, a dual functionality of nanoporous superhydrophobic–hydrophilic micropatterns is demonstrated in their ability to inhibit differentiation of mouse embryonic stem cells (mESCs) and at the same time enable formation of arrays of microdroplets (droplet microarray) via the effect of discontinuous dewetting. Such combination makes high-throughput screening of undifferentiated mouse embryonic stem cells possible. The droplet microarray is used to investigate the development, differentiation, and maintenance of stemness of mESC, revealing the dependence of stem cell behavior on droplet volume in nano- and microliter scale. The inhibition of spontaneous differentiation of mESCs cultured on the droplet microarray for up to 72 h is observed. In addition, up to fourfold increased cell growth rate of mESCs cultured on our platform has been observed. The difference in the behavior of mESCs is attributed to the porosity and roughness of the polymer surface. This work demonstrates that the droplet microarray possesses the potential for the screening of mESCs under conditions of prolonged inhibition of stem cells' spontaneous differentiation. Such a platform can be useful for applications in the field of stem cell research, pharmacological testing of drug efficacy and toxicity, biomedical research as well as in the field of regenerative medicine and tissue engineering.
The demonstrated nanoporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) polymer with defined surface roughness possesses dual functionality enabling the generation of a miniaturized array of multiple droplets on a superhydrophobic–hydrophilic micropattern (droplet microarray) and simultaneously promoting a prolonged inhibition of spontaneous differentiation of mouse embryonic stem cells (mESCs). This renders a miniaturized platform allowing screening of mESC while maintaining their undifferentiated state.
http://ift.tt/2xDDDJz
Development of Antifouling and Bactericidal Coatings for Platelet Storage Bags Using Dopamine Chemistry
Abstract
Platelets have a limited shelf life, due to the risk of bacterial contamination and platelet quality loss. Most platelet storage bags are made of a mixture of polyvinyl chloride with a plasticizer, denoted as pPVC. To improve biocompatibility of pPVC with platelets and to inhibit bacterial biofilm formation, an antifouling polymer coating is developed using mussel-inspired chemistry. A copolymer of N,N-dimethylacrylamide and N-(3-aminopropyl)methacrylamide hydrochloride is synthesized and coupled with catechol groups, named DA51-cat. Under mild aqueous conditions, pPVC is first equilibrated with an anchoring polydopamine layer, followed by a DA51-cat layer. Measurements show this coating decreases fibrinogen adsorption to 5% of the control surfaces. One-step coating with DA51-cat does not coat pPVC efficiently although it is sufficient for coating silicon wafers and gold substrates. The dual layer coating on platelet bags resists bacterial biofilm formation and considerably decreases platelet adhesion. A cationic antimicrobial peptide, E6, is conjugated to DA51-cat then coated on silicon wafers and introduces bactericidal activity to these surfaces. Time-of-flight second ion-mass spectroscopy is successfully applied to characterize these surfaces. pPVC is widely used in medical devices; this method provides an approach to controlling biofouling and bacterial growth on it without elaborate surface modification procedures.
A facile two-step coating of platelet storage bag material with polydopamine and DA51-cat under mild aqueous conditions protects it against fibrinogen adsorption and platelet and bacterial adhesion. Addition of an antimicrobial peptide to DA51-cat introduces bactericidal activity, demonstrating the potential of such an approach for improving platelet storage, one of the challenges in blood product transfusion.
http://ift.tt/2k7uSBU
Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy
Summary
Objective
To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age.
Methods
From 2006–2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs. Brain magnetic resonance imaging (MRI) was assessed using a 0–11 severity score.
Postneonatal seizures, epilepsy rates, and AED treatments were documented. One hundred thirty-four survivors were assessed at 18–24 months; adverse outcome was defined as death or Bayley III composite Cognition/Language or Motor scores <85 and/or severe cerebral palsy or severely reduced vision/hearing. Epilepsy rates in 103 children age 4–8 years were also documented.
Results
aEEG confirmed seizures occurred precooling in 77 (57%) 151 of neonates; 48% had seizures during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18–24 months, one third of infants had an adverse outcome including 11% mortality. At 2 years, 8 (6%) infants had an epilepsy diagnosis (ILAE definition), of whom 3 (2%) received AEDs. Of the 103 4- to 8-year-olds, 14 (13%) had developed epilepsy, with 7 (7%) receiving AEDs. Infants/children on AEDs had higher MRI scores than those not on AEDs (median [interquartile range] 9 [8–11] vs. 2 [0–4]) and poorer outcomes. Nine (64%) of 14 children with epilepsy had cerebral palsy compared to 13 (11%) of 120 without epilepsy, and 10 (71%) of 14 children with epilepsy had adverse outcomes versus 23 (19%) of 120 survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity precooling, and MRI scores predicted childhood epilepsy.
Significance
We report, in a regional cohort of infants cooled for perinatal asphyxia, 6% with epilepsy at 2 years (2% on AEDs) increasing to 13% (7% on AEDs) at early school age. These AED rates are much lower than those reported in the cooling trials, even with adjusting for our cohort′s milder asphyxia. Long-term follow-up is needed to document final epilepsy rates.
http://ift.tt/2fEGEm6
Assessment of Human Adipose Tissue Microvascular Function Using Videomicroscopy
Videomicroscopy systems are used to examine functional properties of isolated adipose tissue arterioles in response to physiological and pharmacological stimuli. This technique can be used to examine microvascular phenotypes in different adipose tissue domains in obese humans.
http://ift.tt/2yLaJF3
Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
http://ift.tt/2ydQi6C
NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma
Abstract
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan–Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16–0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41–0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients.
http://ift.tt/2wnU09j
Chronic liver injury alters driver mutation profiles in hepatocellular carcinoma
Abstract
Most hepatocellular carcinomas (HCCs) develop in a chronically injured liver, yet the extent to which this microenvironment promotes neoplastic transformation or influences selective pressures for genetic drivers of HCC remains unclear. We sought to determine the impact of hepatic injury in an established mouse model of HCC induced by Sleeping Beauty transposon mutagenesis. Chemically-induced chronic liver injury dramatically increased tumor penetrance and significantly altered driver mutation profiles, likely reflecting distinct selective pressures. In addition to established human HCC genes and pathways, we identified several novel injury-associated candidates that represent promising loci for further study. Among them, we found that FIGN is overexpressed in human HCC and promotes hepatocyte invasion. We also validated Gli2's oncogenic potential in vivo, providing direct evidence that Hedgehog signaling can drive liver tumorigenesis in the context of chronic injury. Finally, we show that a subset of injury-associated candidate genes identifies two distinct classes of human HCCs. Further analysis of these two subclasses revealed significant trends among common molecular classification schemes of HCC. The genes and mechanisms identified here provide functional insights into the origin of HCC in a chronic liver damage environment. Conclusion: A chronically damaged liver microenvironment influences the genetic mechanisms that drive hepatocarcinogenesis. This article is protected by copyright. All rights reserved.
http://ift.tt/2hBvmzu
Analysis of the changes in volatile compound and fatty acid profiles of fish oil in chemical refining process
Abstract
In this study, the effect of chemical refining on the volatile compound and fatty acid profiles of crude fish oil was evaluated. The process mainly comprises degumming, deacidification, decoloration, and deodorization. The changes in volatile compounds during the refining process were detected by headspace solid phase micro extraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Meanwhile, the fatty acid profile was determined by GC. The results showed that hexanal, nonanal, undecanal, 2-nonanone, and 2-undecanone are the key volatile components of fish oil, and the relative content of each compound changed significantly in each step. The proportion of polyunsaturated fatty acids (PUFAs) in the refined oil increased, while the proportion of saturated fatty acids (SFAs) reduced significantly. This study provides a theoretical basis for the improvement of sensory characteristics of fish oil via chemical refining.
Practical applications: Chemical refining was employed for improving the characteristics of crude fish oil, mainly including the volatile compound and fatty acid compositions. The result demonstrated that the refining process could affect the volatile compound and fatty acid profiles significantly, which provided the theoretical foundation for the optimization of process conditions.
http://ift.tt/2xHCQ86
Immobilization of Candida rugosa lipase on glutaraldehyde-activated Fe3O4@chitosan as a magnetically separable catalyst for hydrolysis of castor oil
Abstract
In this study, the catalysed hydrolysis of castor oil by Candida rugosa lipase (CRL) immobilized on glutaraldehyde-activated magnetic Fe3O4@chitosan was investigated. Magnetic Fe3O4 was prepared by hydrothermal method and coated with chitosan (CS). Next, CRL was immobilized on Fe3O4@chitosan using glutaraldehyde as a cross-linking reagent. The prepared Fe3O4@CS@CRL was confirmed by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), vibrating sample magnetometry (VSM), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The response surface methodology (RSM) based on the Box–Behnken design was used to evaluate and optimize the hydrolysis reaction variables. The optimum reaction conditions for the hydrolysis of castor oil by the Fe3O4@CS@CRL heterogeneous catalyst were found to be a water/oil ratio of 1.60:1, pH of 7.05, reaction temperature of 34 °C, and lipase concentration of 3.27%; under these conditions, the hydrolysis conversion of castor oil reached 46.81%. Moreover, the immobilized lipase showed high stability with no appreciable loss in its activity after three consecutive cycles.
Practical applications: RSM was found to be a useful technique for optimizing hydrolysis of castor oil. The high conversion of the hydrolysis of castor oil indicates that the Fe3O4@CS@CRL has potential to be used in preparing ricinoleic acid from castor oil. Ricinoleic acid have the potential to be used in printing ink as a pigment and dye disperser, plasticizers, surfactants, lubricants and other valuable products.
http://ift.tt/2wodxGH
Hearing Aids for Mild-to-Moderate Hearing Loss in Adults
A recent systematic review concluded that hearing aid use in older adults with a mild-to-moderate hearing loss was beneficial in improving everyday situations, general health-related quality of life and improve listening ability with little evidence of harm.
http://ift.tt/2fDzezA
Vascular branches from cutaneous nerve of the forearm and hand: Application to better understanding Raynaud's disease
Abstract
Introduction: Cutaneous nerves have branches called vascular branches (VBs) that reach arteries. VBs are thought to be involved in arterial constriction, and this is the rationale for periarterial sympathectomy as a treatment option for Raynaud's disease. However, the branching patterns and distribution areas of the VBs remain largely unclear. The aim of the present study was to investigate the anatomical structures of the VBs of the cutaneous nerves.
Materials and Methods: Forty hands and forearms were examined to assess the branching patterns and distribution areas of the VBs of the superficial branch of the radial nerve (SBRN), the lateral antebrachial cutaneous nerve (LACN), the medial antebrachial cutaneous nerve (MACN), and the palmar cutaneous branch of the ulnar nerve (PCUN).
Results: VBs reaching the radial and ulnar arteries were observed in all specimens. The branching patterns were classified into six types. The mean distance between the radial styloid process and the point where the VBs reached the radial artery was 34.3 ± 4.8 mm in the SBRN and 38.5 ± 15.8 mm in the LACN. The mean distance between the ulnar styloid process and the point where the VBs reached the ulnar artery was 60.3 ± 25.9 mm in the MACN and 43.8 ± 26.0 mm in the PCUN.
Conclusions: This study showed that the VBs of the cutaneous nerves have diverse branching patterns. The VBs of the SBRN had a more limited distribution areas than those of the other nerves. This article is protected by copyright. All rights reserved.
http://ift.tt/2fWK7cC
How to isolate a ready-to-use adipose-derived stem cells pellet for clinical application
Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells (MSCs) that show definitive stem cell characteristics such as plastic adherence in culture, ability to maintain multipotency upon in vitro expansion, and self-renewal capacity. ASCs are particularly promising for use in regenerative medicine because they can be harvested easily from adipose tissue by standard liposuction, with minimal donor site morbidity. Since ASCs do not necessitate ex vivo expansion to obtain clinically significant cell numbers, it is critical to identify a standardized method that maximizes the number of ASCs collected. Based on current literature, there is no standardized method to isolate ASCs for clinical application. Furthermore, clinical studies involving ASCs often show inconsistencies in the reported results. Such studies often use research-derived isolation protocols, which are complex, time-consuming, and involve the use of chemical and animal-derived reagents. In this paper, we present an in-depth review of the available data on ASC isolation protocols. Moreover, we describe our isolation protocol that allows the collection of a ready-to-use ASC pellet for clinical application.
L'articolo How to isolate a ready-to-use adipose-derived stem cells pellet for clinical application sembra essere il primo su European Review.
http://ift.tt/2fDjtZq
Vitamin D in human reproduction: the more, the better? An evidence-based critical appraisal
OBJECTIVE: Vitamin D is a fat-soluble secosteroid hormone that regulates calcium, magnesium, and phosphate homeostasis and plays a pivotal role as antiproliferative and immunomodulatory mediator. Considering the different sources of synthesis and dietary intake as well as the pleiotropic actions in extremely diverse (micro)environments of the body, the supplementation of this Vitamin should be carefully evaluated taking into account the several pathways that it regulates. In the current brief review, we aimed to summarize the available evidence about the topic, in order to suggest the best evidence-based supplementation strategy for human reproduction, avoiding the unuseful (and sometimes hazardous) empiric supplementation.
MATERIALS AND METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.
RESULTS: Accumulating evidence from in vitro fertilization (IVF) trials suggests that fertilization rate decreases significantly with increasing levels of 25OH-D in follicular fluid; in addition, Vitamin D levels in the follicular fluid are negatively correlated to the quality of embryos and the higher values of Vitamin D are associated with lower possibility to achieve pregnancy. Both low and high Vitamin D serum concentrations decrease not only spermatozoa count, but their progressive motility as well as increase morphological abnormalities. Finally, studies in animal models found that severe hypervitaminosis D can reduce the total skeletal calcium store in embryos and may compromise the postnatal survival.
CONCLUSIONS: Based on the retrieved data, we solicit to be extremely selective in deciding for Vitamin D supplementation, since its excess may play a detrimental role in fertility.
L'articolo Vitamin D in human reproduction: the more, the better? An evidence-based critical appraisal sembra essere il primo su European Review.
http://ift.tt/2xLLh45
Itchy gums: Causes, relief, and prevention
Itchy gums can be caused by a range of conditions, from allergies to viral infections. Learn about the symptoms, treatments, and outlook for itchy gums.
http://ift.tt/2xLCG15
Obstructive Sleep Apnea and Diabetes Mellitus. ‘Seeing’ beyond Glycemic Control
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 807-809, October 1, 2017.
http://ift.tt/2xLJPi5
Children’s Urinary Environmental Carbon Load. A Novel Marker Reflecting Residential Ambient Air Pollution Exposure?
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 873-881, October 1, 2017.
http://ift.tt/2fWyfHq
Hyperventilation (Not Ventilator)-induced Lung Injury
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 936-937, October 1, 2017.
http://ift.tt/2xLJfRl
Reply: “A Word of Caution Regarding Patient Self-inflicted Lung Injury and Prophylactic Intubation” and “Hyperventilation (Not Ventilator)-induced Lung Injury”
http://ift.tt/2fWU89F
Inflammatory Myofibroblastic Tumor of the Lung. A Rare Primary Lung Cancer
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 923-924, October 1, 2017.
http://ift.tt/2fVqth0
Mold-Specific Concerns Associated with Water Damage for Those with Allergies, Asthma, and Other Lung Diseases
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page P13-P14, October 1, 2017.
http://ift.tt/2xL4PFy
Integrating Microbiome and Metabolome Data to Understand Infectious Airway Disease
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 806-807, October 1, 2017.
http://ift.tt/2fWAryv
A Word of Caution Regarding Patient Self-inflicted Lung Injury and Prophylactic Intubation
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 936-936, October 1, 2017.
http://ift.tt/2xLDfrU
Evaluating Molecular Biomarkers for the Early Detection of Lung Cancer: When Is a Biomarker Ready for Clinical Use? An Official American Thoracic Society Policy Statement
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page e15-e29, October 1, 2017.
http://ift.tt/2fXl4Gq
Looking beyond the Tip of a Tusk: Balancing the Evidence in Prognosis-related Communication
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 803-804, October 1, 2017.
http://ift.tt/2fVRRvh
The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil’s Advocate
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 934-935, October 1, 2017.
http://ift.tt/2xLrEZH
Impact of Point-of-Care Xpert MTB/RIF on Tuberculosis Treatment Initiation. A Cluster-randomized Trial
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 901-910, October 1, 2017.
http://ift.tt/2fVRj8H
Physiology of Arousal in Obstructive Sleep Apnea and Potential Impacts for Sedative Treatment
http://ift.tt/2xLBGKA
Antibiotics for Sepsis: Does Each Hour Really Count, or Is It Incestuous Amplification?
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 800-802, October 1, 2017.
http://ift.tt/2xLD8N0
Insights into Asthma Therapies, Cardiovascular Effects, and Mechanisms from Recent Clinical Trials
http://ift.tt/2fXkvvW
Effects of Retinoids on Augmentation of Club Cell Secretory Protein
http://ift.tt/2xLmVr6
Reply: The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil’s Advocate
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 935-936, October 1, 2017.
http://ift.tt/2xLy4b6
Obstructive Sleep Apnea and Retinopathy in Patients with Type 2 Diabetes. A Longitudinal Study
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 892-900, October 1, 2017.
http://ift.tt/2fWS5Cu
New Guidelines on Noninvasive Ventilation. A Few Answers, and Several More Questions
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page 811-813, October 1, 2017.
http://ift.tt/2xL4EtS
An Adolescent with Dyspnea and Cough. A Case of Congenital Tracheal Stenosis
American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 7, Page e30-e31, October 1, 2017.
http://ift.tt/2fXdZp2
October Highlights/Papers by Junior Investigators/NIH News
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page iv-iv, October 2017.
http://ift.tt/2xHk80k
Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 448-458, October 2017.
http://ift.tt/2wnu3Xl
Integrative Genomics of Emphysema-Associated Genes Reveals Potential Disease Biomarkers
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 411-418, October 2017.
http://ift.tt/2xGPeVJ
Hydrogen Sulfide: A Novel Player in Airway Development, Pathophysiology of Respiratory Diseases, and Antiviral Defenses
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 403-410, October 2017.
http://ift.tt/2woQ8F8
Dendritic Cell Trafficking and Function in Rare Lung Diseases
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 393-402, October 2017.
http://ift.tt/2xGgljK
A Novel In Vitro Human Granuloma Model of Sarcoidosis and Latent Tuberculosis Infection
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 487-498, October 2017.
http://ift.tt/2wp75is
Integrative Genomics of Emphysema-Associated Genes: Are We Closer to Identifying the Genetic Determinants of Lung Function?
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 377-378, October 2017.
http://ift.tt/2xI0KAi
A Tale of Two Endoglins: How Does Tail-Less Soluble Endoglin Deregulate Lung Development?
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 388-390, October 2017.
http://ift.tt/2wo8Rk4
Activation of the Integrated Stress Response and Metabolic Dysfunction in a Murine Model of Sleep Apnea
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 477-486, October 2017.
http://ift.tt/2xHyNsA
Does Granulocyte–Macrophage Colony-Stimulating Factor Coordinate a Hepatopulmonary Axis of Lipid Metabolism?
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 4, Page 383-385, October 2017.
http://ift.tt/2woOJhP
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
