Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Abstract

Background

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain.

Methods

We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.

Results

Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration.

Conclusions

Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease.

http://ift.tt/2zMIKsL

Detection of Helicobacter pylori in stool samples of young children using real-time polymerase chain reaction

Abstract

Background

The aims of this study were to develop and validate a multiplex real-time polymerase chain reaction (q-PCR) assay of Helicobacter pylori in stool samples of healthy children. Additionally, we determined the prevalence of clarithromycin resistance and cagA gene in H. pylori-positive samples.

Materials and methods

Archived stool samples from 188 children aged 6-9 years and 272 samples of 92 infants aged 2-18 months were tested for H. pylori antigens using enzyme immunoassay (EIA). A multiplex q-PCR assay was designed to detect H. pylori 16S rRNA and urease and the human RNase P gene as an internal control. Kappa coefficient was calculated to assess the agreement between q-PCR and EIA.

Results

Laboratory validation of the q-PCR assay using quantitated H. pylori ATCC 43504 extracted DNA showed S-shaped amplification curves for all genes; the limit of detection was 1 CFU/reaction. No cross-reactivity with other bacterial pathogens was noted. Applying the multiplex q-PCR to DNA extracted from fecal samples showed clear amplification curves for urease gene, but not for 16S rRNA. The prevalence of H. pylori infection was 50% (95% CI 43%-57%) by q-PCR (urease cycle threshold <44) vs 59% (95% CI 52%-66%) by EIA. Kappa coefficient was .80 (P < .001) and .44 (P < .001) for children aged 6-9 years and 2-18 months, respectively. Sixteen samples were positive for cagA and three were positive for clarithromycin resistance mutation (A2143G) as confirmed by sequencing.

Conclusions

The developed q-PCR can be used as a cotechnique to enhance the accuracy of H. pylori detection in epidemiological studies and in clinical settings.

http://ift.tt/2nbudB6

Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Abstract

Background

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain.

Methods

We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.

Results

Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration.

Conclusions

Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease.

http://ift.tt/2zMIKsL

Detection of Helicobacter pylori in stool samples of young children using real-time polymerase chain reaction

Abstract

Background

The aims of this study were to develop and validate a multiplex real-time polymerase chain reaction (q-PCR) assay of Helicobacter pylori in stool samples of healthy children. Additionally, we determined the prevalence of clarithromycin resistance and cagA gene in H. pylori-positive samples.

Materials and methods

Archived stool samples from 188 children aged 6-9 years and 272 samples of 92 infants aged 2-18 months were tested for H. pylori antigens using enzyme immunoassay (EIA). A multiplex q-PCR assay was designed to detect H. pylori 16S rRNA and urease and the human RNase P gene as an internal control. Kappa coefficient was calculated to assess the agreement between q-PCR and EIA.

Results

Laboratory validation of the q-PCR assay using quantitated H. pylori ATCC 43504 extracted DNA showed S-shaped amplification curves for all genes; the limit of detection was 1 CFU/reaction. No cross-reactivity with other bacterial pathogens was noted. Applying the multiplex q-PCR to DNA extracted from fecal samples showed clear amplification curves for urease gene, but not for 16S rRNA. The prevalence of H. pylori infection was 50% (95% CI 43%-57%) by q-PCR (urease cycle threshold <44) vs 59% (95% CI 52%-66%) by EIA. Kappa coefficient was .80 (P < .001) and .44 (P < .001) for children aged 6-9 years and 2-18 months, respectively. Sixteen samples were positive for cagA and three were positive for clarithromycin resistance mutation (A2143G) as confirmed by sequencing.

Conclusions

The developed q-PCR can be used as a cotechnique to enhance the accuracy of H. pylori detection in epidemiological studies and in clinical settings.

http://ift.tt/2nbudB6

A review on pesticide removal through different processes

Abstract

The main organic pollutants worldwide are pesticides, persistent chemicals that are of concern owing to their prevalence in various ecosystems. In nature, pesticide remainders are subjected to the chemical, physical, and biochemical degradation process, but because of its elevated stability and some cases water solubility, the pesticide residues persist in the ecosystem. The removal of pesticides has been performed through several techniques classified under biological, chemical, physical, and physicochemical process of remediation from different types of matrices, such as water and soil. This review provides a description of older and newer techniques and materials developed to remove specific pesticides according to previous classification, which range from bioremediation with microorganisms, clay, activated carbon, and polymer materials to chemical treatment based on oxidation processes. Some types of pesticides that have been removed successfully to large and small scale include, organophosphorus, carbamates, organochlorines, chlorophenols, and synthetic pyrethroids, among others. The most important characteristics, advantages, and disadvantages of techniques and materials for removing pesticides are described in this work.

http://ift.tt/2BhsfRG

Correction to: Heavy metal and nutrient uptake in plants colonizing post-flotation copper tailings

Abstract

The correct presentation of Table 4 is shown in this paper.

http://ift.tt/2iWW97a

Study on the pollution status and control measures for the livestock and poultry breeding industry in northeastern China

Abstract

Livestock and poultry breeding industry is one of the main economic pillars of northeastern China. However, the amount of pollutants produced is much higher than that in other parts of China. Through a questionnaire survey, indoor experiment, and outdoor experiment, it was found that the resource utilization rate of livestock and poultry manure in the northeastern region is low, with the pollution of livestock and poultry breeding mainly including air and water pollution. The alarm level of cultivated land and manure is II. While the livestock and poultry breeding is relatively concentrated area, its level is higher than grade II. Based on the pollution status of small farms, biogas can be produced through fermentation, along with the preparation of organic fertilizer, to completely utilize the manure and straw, while obtaining higher economic value, and effectively controlling the pollution from livestock and poultry breeding.

http://ift.tt/2BhrQ1C

Correction to: Strict anaerobic side-stream reactor: effect of the sludge interchange ratio on sludge reduction in a biological nutrient removal process

Abstract

The correct Fig. 1 is shown in this paper.

http://ift.tt/2iYdjkI

Pirfenidone-induced hyponatraemia: insight in mechanism, risk factor and management

Pirfenidone was approved in October 2014 in the USA for the treatment of idiopathic pulmonary fibrosis. Although not included in the adverse events published in the CAPACITY-1 and CAPACITY-2 or ASCEND trials, hyponatraemia was reported in supplementary data with rate of 3.4% in the active therapy arm versus 0.3% in the placebo arm. We performed a retrospective analysis of patients who were initiated on pirfenidone or nintedanib for the treatment of pulmonary fibrosis at our centre. Of the 52 patients who were started on pirfenidone, three (5.8%) developed severe hyponatraemia. Of the 29 patients who were started on nintedanib, none developed hyponatraemia. Laboratory data suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by pirfenidone and the medication was discontinued. Hyponatraemia is a possible significant adverse effect of pirfenidone, able to induce SIADH in patients taking the medication.

http://ift.tt/2ADFkZl

Puff laddy: a 5-year-old-boy with forehead swelling

Description

A 5-year-old boy presented with forehead swelling in the setting of a recent sinus infection. His initial symptoms were fever and nasal congestion for which he was prescribed a 10-day course of antibiotics, completed 3 days prior to admission. He subsequently developed unsteady gait, photophobia, headache, vomiting and progressive forehead swelling. He was noted to have central forehead oedema and tenderness without overlying erythaema (figure 1). There were no neurological or ophthalmological deficits. Magnetic Resonance Imaging (MRI)/Magnetic Resonance Venography (MRV) of the head demonstrated a 3.5x1.2x3.9 cm subgaleal abscess with communication to the frontal sinuses as well as osteomyelitis of the frontal bone (figure 2). The patient underwent surgical drainage of the abscess with evacuation of purulent fluid (figure 3). Culture from the procedure grew Streptococcus anginosus. He clinically improved following surgery and was transitioned home to complete a 21-day total course of antibiotics.

...

http://ift.tt/2Aaows5

Brief psychotic episode in a patient with chromosome 2q37 microdeletion syndrome

A 21-year-old woman with moderate learning disability secondary to chromosome 2 microdeletion at q37 was admitted to a general adult psychiatric ward following a period of agitation with incessant pressure of speech, nihilistic delusions and worsening of sleep and eating patterns. Her presentation was preceded for a number of weeks by social stressors of an ill family member and another family member moving away. She had also been diagnosed and treated for a respiratory infection several weeks prior to presentation. Her presentation improved with low-dose antipsychotic medication and parallel input from the general adult mental health team and the psychiatry of intellectual disability team.

http://ift.tt/2icwH0x

Treatment of advanced colorectal cancer in a patient with cardiotoxic reactions to 5-fluorouracil and capecitabine using suboptimal doses

A 32-year-old female with stage IV colorectal cancer and metastasis to the liver experienced cardiotoxic reactions after treatment with 5-fluorouracil and its oral prodrug capecitabine even at two-thirds the recommended dose. After careful considerations, the decision was made to attempt capecitabine retrial at a further suboptimal dose with combination chemotherapy where she no longer experienced cardiac events. As a result, the liver tumour shrank and rectal mass stabilised, tumour markers dropped and she underwent surgical resection of both masses. Later there was local recurrence of disease near the previous liver tumour, so the suboptimal capecitabine therapy was restarted without complaint. The patient became a candidate for a NanoKnife procedure, offering a potentially curative therapy. This case report summarises a novel treatment strategy for those patients with advanced colorectal cancer who experience cardiotoxic reactions to fluoropyrimidines, the active agent of gold standard treatment.

http://ift.tt/2k3QBLr

Dying art of a history and physical: pulsatile tinnitus

Modern medicine often leaves the history and physical by the wayside. Physicians instead skip directly to diagnostic modalities like MRI and angiography. In this case report, we discuss a patient who presented with migraine symptoms. Auscultation revealed signs of pulsatile tinnitus. Further imaging concluded that it was secondary to a type I dural arteriovenous fistula. Thanks to a proper and thorough history and physical, the patient was streamlined into an accurate and efficient work-up leading to symptomatic relief and quality of life improvement. Imaging is a powerful adjunctive technique in modern medicine, but physicians must not rely on machines to diagnose their patients. If this trend continues, it will have a tremendous negative impact on the cost and calibre of healthcare. Our hope is that this case will spread awareness in the medical community, urging physicians to use the lost art of a history and physical.

http://ift.tt/2i9XXws

Inverse hypopyon (hyperoleon) at the posterior segment in pathological myopia

Description

A 54-year-old woman presented a year after vitreoretinal surgery with silicone oil injection in the left eye. The left eye showed emulsified silicone oil in the anterior chamber and a posterior chamber intraocular lens. The fundus revealed a posterior staphyloma, attached retina and whitish emulsified silicone bubbles with a horizontal lower border giving rise to inverse hypopyon in the posterior pole (figure 1).

Figure 1

The fundus photo shows chorioretinal atrophy temporal to the optic disc and emulsified silicone oil bubbles with a horizontal lower level suggestive of inverse hypopyon.

Inverted hypopyon at the posterior pole1 is a rare finding which can be seen in patients with posterior staphyloma and long-term silicone oil tamponade.2 The emulsified silicone oil being lighter than fluid floats superiorly giving rise to this appearance mostly in the anterior segment (hyperoleon).

http://ift.tt/2k3Qwr7

Rare and unusual case of perforated appendicitis in a Spigelian hernia

Background

Amyand hernia is a rare phenomenon, defined as an inguinal hernia containing the vermiform appendix. It is seen in less than 1% of inguinal hernias. Claudius Amyand first reported this interesting finding in 1735.

De Garengeot hernia: this is the clinical finding of the vermiform appendix within a femoral hernia sac; it occurs in less than 1% of all femoral hernias and is named after the French surgeon, Rene Jacques Croissant de Garengeot.

Unnamed: The clinical entity we describe in this case report is the last of the 'appendix in a hernia—yet to be eponymously named'. It is an interesting and intriguing clinical finding, yet without a referenced name it does not immediately come to mind as a potential differential diagnosis. Medical historians may well commence the search for the first description of the condition.

Case presentation

An 83-year-old woman was admitted to the...

http://ift.tt/2ibG5Bw

Fish hook injury: an easy removal using the string yank technique

Description

An embedded fish hook injury is a tough condition for clinical decision-making, as it needs to be determined whether to advance the hook or to pull it out. Patients or their friends usually attempt to remove a fish hook, causing more soft tissue trauma. There are many different sizes and types of fish hooks, and the four main techniques for their removal are (1) retrograde technique for barbless and superficially embedded hooks, (2) needle cover technique for large hooks with a single barb, (3) advance and cut technique for large fish hooks with potential additional trauma and (4) string yank technique for superficially embedded, small-sized to medium-sized fish hooks.1 The technique of removal should be selected based on the size and shape of a fish hook and the anatomical condition of the injury. Here, we report a useful technique for primary care physicians, accompanied by an instructional video given in the online...

http://ift.tt/2k3ZZyS

Paediatric Salter-Harris type IV injury of distal tibia with talus fracture

Fracture of talus with Salter-Harris injury of the distal end of tibia is a rare injury in paediatric age group. The authors report a case of a 13-year-old male child who sustained type IV Salter-Harris injury to the medial malleolus with coronal spilt along with spilt and depressed fracture of the neck of talus and fracture of the lateral process of talus with stable compression fracture of spine sustained due to fall from 6 meters height. CT scan delineated the morphology of fracture pattern and helped in preoperative planning. Talar articular fracture was reduced and fixed arthroscopically while distal tibial fracture was fixed under image intensifier. We observed favourable outcome following arthroscopic reduction at 4-year follow-up.

http://ift.tt/2ia7zY5

Lesion in the external auditory canal: an unusual site for basal cell carcinoma

Description

An 85-year-old woman presented to the ear, nose and throat clinic with a 2-week history of left-sided otorrhoea and pruritus of the ear. Examination of the left external auditory canal (EAC) revealed a polypoidal lesion and purulent discharge (figure 1). The tympanic membrane was intact. The suspicious lesion prompted imaging, including CT neck and thorax (figure 2). An ultrasound scan of the parotid and neck showed no metastatic disease. A biopsy was undertaken and histology demonstrated a basal cell carcinoma (BCC). The patient was managed with a staged procedure. Stage 1 consisted of a wide local excision of the BCC, with a 4 mm margin. Frozen section was not available; therefore, a second stage was needed to achieve clear margins using a sleeve resection. Fortunately, the disease was limited to the cartilaginous ear canal, hence did not require further resection or reconstruction. This management...

http://ift.tt/2k3ZMM6

Puzzling thyroid function test

A 13-1/2-year-old boy was referred to the Department of Endocrinology as a case of thyrotoxicosis for initiation of antithyroid medication. His chief complaint was a swelling in front of the neck, which was incidentally noted by his mother 2 weeks prior to presentation. He denied any history of symptoms suggestive of hyperthyroidism or ophthalmological involvement. His physical examination was unremarkable except for a grade 2 goitre. Thyroid function test revealed elevated free triiodothyronine and tetraiodothyronine in the face of an unsuppressed thyroid-stimulating hormone level. Technetium-99 uptake scan showed increased uptake indicating enhanced thyroid activity. However, he was clinically euthyroid. This raised the possibility of resistance to thyroid hormones, which was confirmed by documenting similar thyroid function test abnormalities in other members of his family and genetic testing. The family was reassured of the benign nature of the condition.

http://ift.tt/2i9XFpm

Cancer-related microangiopathic haemolytic anaemia

Description

A 71-year-old woman with widely metastatic breast cancer to liver and bone marrow presented with 2 weeks of fatigue. Examination revealed a severely ill-appearing woman in moderate distress with icterus and jaundice. Laboratory investigations revealed profound anaemia (haemoglobin 5.2 g/dL) with appropriate reticulocyte response (14.4%) and a normal platelet count (207x 10⁹/L). Additional tests revealed a lactate dehydrogenase of 2997 IU/L (normal: 140–297 IU/L), negative direct Coombs antiglobulin, an undetectable haptoglobin level, elevated total bilirubin, newly elevated prothrombin time (19.7 s, normal: <14.1 s), elevated fibrin split products and D-dimer (14.36 µg/dL, normal: <0.53 µg/dL) but normal fibrinogen level (322 mg/dL, normal: 193–488 mg/dL). Peripheral blood smear revealed marked schistocytosis (figure 1) with normal platelet count. The patient was diagnosed with cancer-associated microangiopathic haemolytic anaemia1 2 with laboratory evidence of disseminated intravascular coagulation, and she passed away on comfort measures 24 hours after admission.

Figure 1

Arrows showing marked schistocytes.

...

http://ift.tt/2k3ZHbg

Delayed presentation of iatrogenic bladder perforation

Description 

A 41-year-old lady presented to a district general hospital with a 24-hour history of abdominal pain, shoulder tip pain and anuria. No other symptoms were reported, and observations were stable. Her medical history included endometriosis, one normal vaginal delivery in 1998 and three caesarean sections dated 2003, 2010 and 2012. On examination, there was tenderness in the suprapubic region and left loin; the bladder was not palpable, and she did not elicit any signs of peritonitis. A Foley catheter was inserted. Urinalysis showed 4+ blood and 2+ ketones. She had raised inflammatory markers and a raised creatinine of 200 µmol/L.

The following day, creatinine had normalised, but there was no improvement in symptoms, despite antibiotics. A CT of her kidneys, ureters and bladder was reported as showing locules of free gas in the bladder consistent with recent catheterisation. There was free fluid in the pelvis, and a faecolith...

http://ift.tt/2icfjIY

Quantitative CT assessment of a novel direction-modulated brachytherapy tandem applicator

Publication date: Available online 27 November 2017
Source:Brachytherapy
Author(s): Alyaa H. Elzibak, Petronella M. Kager, Abraam Soliman, Moti R. Paudel, Habib Safigholi, Dae Yup Han, Aliaksandr Karotki, Ananth Ravi, William Y. Song
PurposeThe purpose of this study was to quantitatively assess the CT metal-induced artifacts from a novel direction-modulated brachytherapy (DMBT) tandem applicator prototype, recently designed for cervical cancer treatments.Methods and materialsA water-based pelvic phantom was constructed for CT scanning. The DMBT applicator was imaged using our institutional protocol, one with higher kVp and mAs settings, and repetition of these protocols using 3-mm slices. A conventional stainless steel applicator was also scanned. In addition to the standard reconstructed images, applicator images were reconstructed using a commercial metal artifact-reduction (MAR) algorithm and an in-house–developed research algorithm. Subsequently, image quality and artifact severity were evaluated.ResultsArtifact severity, measured in terms of SDs in CT numbers, decreased asymptotically to background water levels with the distance away from the applicator. Artifact-reduction algorithms lead to significant and visible improvements in image quality, with >50% and >20% decrease in artifact severity achieved at a 10-mm distance for the DMBT and stainless steel applicators, respectively. Differences in artifact severity were minimal between the four imaging protocols. DMBT dimensions were the same on images with and without the commercial MAR algorithm, within <1 mm of the theoretical value. Both the commercial and in-house algorithms restored the CT numbers outside the applicator, albeit a better performance was achieved by the in-house algorithm.ConclusionsThe artifacts produced by both applicators were minimized with the use of MAR algorithms. Adoption of the DMBT and stainless steel applicators for CT-guided brachytherapy is anticipated as MAR algorithms are widely available on CT scanners.



http://ift.tt/2zMCdyf

Rhabdomyolysis, lactic acidosis, and multiple organ failure during telbivudine treatment for hepatitis B: a case report and review of the literature

Telbivudine can cause severe side effects, including myositis, neuritis, rhabdomyolysis, and lactic acidosis. However, reported cases of telbivudine leading to multiple organ failure are rare. Here, we report ...

http://ift.tt/2zLcYMI

The Ventral Posterior Lateral Thalamus Preferentially Encodes Externally Applied Versus Active Movement: Implications for Self-Motion Perception

Abstract

Successful interaction with our environment requires that voluntary behaviors be precisely coordinated with our perception of self-motion. The vestibular sensors in the inner ear detect self-motion and in turn send projections via the vestibular nuclei to multiple cortical areas through 2 principal thalamocortical pathways, 1 anterior and 1 posterior. While the anterior pathway has been extensively studied, the role of the posterior pathway is not well understood. Accordingly, here we recorded responses from individual neurons in the ventral posterior lateral thalamus of macaque monkeys during externally applied (passive) and actively generated self-motion. The sensory responses of neurons that robustly encoded passive rotations and translations were canceled during comparable voluntary movement (~80% reduction). Moreover, when both passive and active self-motion were experienced simultaneously, neurons selectively encoded the detailed time course of the passive component. To examine the mechanism underlying the selective elimination of vestibular sensitivity to active motion, we experimentally controlled correspondence between intended and actual head movement. We found that suppression only occurred if the actual sensory consequences of motion matched the motor-based expectation. Together, our findings demonstrate that the posterior thalamocortical vestibular pathway selectively encodes unexpected motion, thereby providing a neural correlate for ensuring perceptual stability during active versus externally generated motion.

http://ift.tt/2ibt2jB

Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis of the Volume of the Cerebral Cortex

Abstract

Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features.

http://ift.tt/2Ad4a1J

Human Cortical Thickness Organized into Genetically-determined Communities across Spatial Resolutions

Abstract

The cerebral cortex may be organized into anatomical genetic modules, communities of brain regions with shared genetic influences via pleiotropy. Such modules could represent novel phenotypes amenable to large-scale gene discovery. This modular structure was investigated with network analysis of in vivo MRI of extended pedigrees, revealing a "multiscale" structure where smaller and larger modules exist simultaneously and in partially overlapping fashion across spatial scales, in contrast to prior work suggesting a specific number of cortical thickness modules. Inter-regional genetic correlations, gene co-expression patterns and computational models indicate that two simple organizational principles account for a large proportion of the apparent complexity in the network of genetic correlations. First, regions are strongly genetically correlated with their homologs in the opposite cerebral hemisphere. Second, regions are strongly genetically correlated with nearby regions in the same hemisphere, with an initial steep decrease in genetic correlation with anatomical distance, followed by a more gradual decline. Understanding underlying organizational principles of genetic influence is a critical step towards a mechanistic model of how specific genes influence brain anatomy and mediate neuropsychiatric risk.

http://ift.tt/2ibt0Iv

The Neural Correlates of Intelligence Comparison

Abstract

Social comparison plays an important role in our daily life. Several studies have investigated the neural mechanism of social comparison; however, their conclusions remain controversial. The present study explored the neural correlates of intelligence comparison and nonsocial size comparison using functional magnetic resonance imaging and a distance effect paradigm. We found that both intelligence and size comparisons obeyed the behavioral distance effect—longer response times for near than far distances and this effect involved an overlapping frontal network including the dorsomedial prefrontal cortex and insula. In addition, compared with size comparisons, intelligence comparisons elicited increased activity in the precuneus and angular gyrus, but decreased activity in the inferior parietal lobe. Furthermore, the analysis of seed-based functional connectivity complemented these neural commonalities and differences. Our findings suggest that social and nonsocial comparisons may rely on a common core mechanism, but this mechanism may be supplemented by different domain-specific cognitive components.

http://ift.tt/2AbBWob

Major Feedforward Thalamic Input Into Layer 4C of Primary Visual Cortex in Primate

Abstract

One of the underlying principles of how mammalian circuits are constructed is the relative influence of feedforward to recurrent synaptic drive. It has been dogma in sensory systems that the thalamic feedforward input is relatively weak and that there is a large amplification of the input signal by recurrent feedback. Here we show that in trichromatic primates there is a major feedforward input to layer 4C of primary visual cortex. Using a combination of 3D-electron-microscopy and 3D-confocal imaging of thalamic boutons we found that the average feedforward contribution was about 20% of the total excitatory input in the parvocellular (P) pathway, about 3 times the currently accepted values for primates. In the magnocellular (M) pathway it was around 15%, nearly twice the currently accepted values. New methods showed the total synaptic and cell densities were as much as 150% of currently accepted values. The new estimates of contributions of feedforward synaptic inputs into visual cortex call for a major revision of the design of the canonical cortical circuit.

http://ift.tt/2icrgi9

Developmental Connectivity and Molecular Phenotypes of Unique Cortical Projection Neurons that Express a Synapse-Associated Receptor Tyrosine Kinase

Abstract

The complex circuitry and cell-type diversity of the cerebral cortex are required for its high-level functions. The mechanisms underlying the diversification of cortical neurons during prenatal development have received substantial attention, but understanding of neuronal heterogeneity is more limited during later periods of cortical circuit maturation. To address this knowledge gap, connectivity analysis and molecular phenotyping of cortical neuron subtypes that express the developing synapse-enriched MET receptor tyrosine kinase were performed. Experiments used a Met^GFP transgenic mouse line, combined with coexpression analysis of class-specific molecular markers and retrograde connectivity mapping. The results reveal that MET is expressed by a minor subset of subcerebral and a larger number of intratelencephalic projection neurons. Remarkably, MET is excluded from most layer 6 corticothalamic neurons. These findings are particularly relevant for understanding the maturation of discrete cortical circuits, given converging evidence that MET influences dendritic elaboration and glutamatergic synapse maturation. The data suggest that classically defined cortical projection classes can be further subdivided based on molecular characteristics that likely influence synaptic maturation and circuit wiring. Additionally, given that MET is classified as a high confidence autism risk gene, the data suggest that projection neuron subpopulations may be differentially vulnerable to disorder-associated genetic variation.

http://ift.tt/2Ab9Rxf

Cortical Phase–Amplitude Coupling in a Progressive Model of Parkinsonism in Nonhuman Primates

Abstract

Parkinson's disease is associated with abnormal oscillatory electrical activities of neurons and neuronal ensembles throughout the basal ganglia-thalamocortical network. It has recently been documented in patients with advanced parkinsonism that the amplitude of gamma-band oscillations (50–200 Hz) in electrocorticogram recordings from the primary motor cortex is abnormally coupled to the phase of beta band oscillations within the same signals. It is not known when in the course of the disease the abnormal phase–amplitude coupling (PAC) arises, and whether it is influenced by arousal or prior exposure to dopaminergic medications. To address these issues, we analyzed the relationship between the severity of parkinsonian motor signs and the extent of PAC in a progressive model of parkinsonism, using primates that were not exposed to levodopa prior to testing. PAC was measured in electrocorticogram signals from the primary motor cortex and the supplementary motor area in 3 monkeys that underwent weekly injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rendering them progressively parkinsonian. We found that parkinsonism was associated with increased coupling between the phase of low-frequency (4–10 Hz) oscillations and the amplitude of oscillations in the high gamma band (50–150 Hz). These changes only reached significance when the animals became fully parkinsonian. The increased PAC was normalized after levodopa treatment. We also found a similar increase in PAC during sleep, even in normal animals. The identified PAC was independent of concomitant changes in spectral power in the 2.9–9.8Hz or 49.8–150.4 Hz ranges. We conclude that PAC is predominately a sign of advanced parkinsonism, and is, thus, not essential for the development of parkinsonism. However, increased PAC appears to correlate with the severity of fully developed parkinsonism.

http://ift.tt/2icx4rW

Slow Waves in Cortical Slices: How Spontaneous Activity is Shaped by Laminar Structure

Abstract

Cortical slow oscillations (SO) of neural activity spontaneously emerge and propagate during deep sleep and anesthesia and are also expressed in isolated brain slices and cortical slabs. We lack full understanding of how SO integrate the different structural levels underlying local excitability of cell assemblies and their mutual interaction. Here, we focus on ongoing slow waves (SWs) in cortical slices reconstructed from a 16-electrode array designed to probe the neuronal activity at multiple spatial scales. In spite of the variable propagation patterns observed, we reproducibly found a smooth strip of loci leading the SW fronts, overlapping cortical layers 4 and 5, along which Up states were the longest and displayed the highest firing rate. Propagation modes were uncorrelated in time, signaling a memoryless generation of SWs. All these features could be modeled by a multimodular large-scale network of spiking neurons with a specific balance between local and intermodular connectivity. Modules work as relaxation oscillators with a weakly stable Down state and a peak of local excitability to model layers 4 and 5. These conditions allow for both optimal sensitivity to the network structure and richness of propagation modes, both of which are potential substrates for dynamic flexibility in more general contexts.

http://ift.tt/2AewUac

The Computational Anatomy of Visual Neglect

Abstract

Visual neglect is a debilitating neuropsychological phenomenon that has many clinical implications and—in cognitive neuroscience—offers an important lesion deficit model. In this article, we describe a computational model of visual neglect based upon active inference. Our objective is to establish a computational and neurophysiological process theory that can be used to disambiguate among the various causes of this important syndrome; namely, a computational neuropsychology of visual neglect. We introduce a Bayes optimal model based upon Markov decision processes that reproduces the visual searches induced by the line cancellation task (used to characterize visual neglect at the bedside). We then consider 3 distinct ways in which the model could be lesioned to reproduce neuropsychological (visual search) deficits. Crucially, these 3 levels of pathology map nicely onto the neuroanatomy of saccadic eye movements and the systems implicated in visual neglect.

http://ift.tt/2icaTSy

Nickle(II) ions exacerbate bleomycin-induced pulmonary inflammation and fibrosis by activating the ROS/Akt signaling pathway

Abstract

Nickle (Ni) is a heavy metal found in particulate matter. We previously reported that Ni ions are strongly associated with high apoptosis rates and high expression of IL-1β in human bronchial epithelial cells following exposure to PM2.5; however, the effects of Ni ions on pulmonary fibrosis have not been fully elucidated. In the current study, we evaluated whether Ni ions can exacerbate bleomycin (BLM)-induced pulmonary fibrosis in a mouse model and illustrated the potential mechanism. Ni ions inhibited cell proliferation and induced apoptosis in A549 and MRC-5 cells. BLM-induced lung injury and fibrosis in mice were significantly enhanced by nickel treatment, and these findings were also supported by inflammatory cell accumulation in bronchoalveolar lavage fluid and elevated levels of pro-inflammatory cytokines in lung tissues. Ni ions also increased extracellular matrix protein levels, including those of type I collagen and MMP9 in mouse lung tissues and cell lines. Moreover, Ni ions promoted the phosphorylation of AKT in this mouse model. The effect of increased collagen levels and MMP9 expression was inhibited by blocking the AKT phosphorylation. Together, these findings suggest AKT activation as a critical contributor to this Ni-exacerbated pulmonary fibrotic process.

http://ift.tt/2zLCEck

Heterogeneous activation of peroxymonosulfate by hierarchical CuBi 2 O 4 to generate reactive oxygen species for refractory organic compounds degradation: morphology and surface chemistry derived reaction and its mechanism

Abstract

Activation of peroxymonosulfate (PMS) by a novel hierarchical CuBi₂O₄ generated reactive oxygen radical for degradation refractory organic compounds in aqueous solution, which would be controlled by the morphology and surface chemistry of solid catalyst. It's found that the activation ability of CuBi₂O₄ toward PMS was highly dependent on the morphology and surface hydroxyl group, as using rhodamine B (RhB) as the model compound. The spherical CuBi₂O₄, which possessed higher density of surface hydroxyl group, exhibited better catalytic activity in RhB degradation than scattered cluster CuBi₂O₄, and as-prepared CuBi₂O₄ could efficiently activated PMS to degrade RhB within a wide pH range as an absolute heterogeneous process. The emerging organic chemicals, including bisphenol A, 1H-benzotriazole, and carbamazepine, could also be effectively removed in this novel CuBi₂O₄/PMS. Furthermore, activation mechanism of PMS by as-prepared CuBi₂O₄ was proposed, the existence of surface hydroxyl group bonded with Cu(II), and inward electron transfer cycling reaction between Cu(II)/Cu(I) facilitated the effective activation of PMS to generate SO₄^·− and ·OH. In addition, the intermediates of RhB formed in this process were identified by silylation derivatation-GC-MS and LC-high-resolution MS/MS, and degradation pathway was proposed.

http://ift.tt/2nbndnB

Analysis of the characteristics of cracked teeth and evaluation of pulp status according to periodontal probing depth

Abstract

Background

The purpose of this study was to analyze the characteristics of cracked teeth and to evaluate pulp status according to periodontal probing depth (PPD).

Methods

A total of 182 cracked teeth were included. The location and type of the cracked teeth, age and gender of the patients, restoration type, pulp status, PPD, and radiographic findings were analyzed.

Results

Mandibular second molars (25.3%) were the most frequently involved teeth, followed by mandibular first molars (22.5%), maxillary first molars (22.0%), and maxillary second molars (17.6%). The patient age was most frequently 50–59 years. Cracks occurred mainly in nonbonded restorations, such as gold (26.9%), and were usually found in intact teeth (37.9%). A total of 103 teeth (56.6%) had an initial PPD of less than 3 mm, while 40 (22.0%) had a PPD of 4–6 mm, and 39 (21.4%) had PPD of 7 mm or more. A total of 33 cracked teeth (18.1%) were diagnosed with pulp necrosis, 40 (22.0%) with irreversible pulpitis, and 97 (53.3%) with reversible pulpitis. The incidence of pulp necrosis was 31.8% among cracked teeth with a PPD of 4–6 mm, and 28.6% among those with a PPD of 7 mm or more.

Conclusions

Cracks occurred mainly in molar teeth, and were commonly found in intact teeth with no restoration. Patients with cracked teeth were most frequently aged 50–59 years. Cracked teeth showing a PPD of more than 4 mm were more likely to show pulp necrosis.

http://ift.tt/2AaaCWS

The costs and benefits of water fluoridation in NZ

Abstract

Background

Implementing community water fluoridation involves costs, but these need to be considered against the likely benefits. We aimed to assess the cost-benefit and cost-effectiveness of water fluoridation in New Zealand (NZ) in terms of expenditure and quality-adjusted life years.

Methods

Based on published studies, we determined the risk reduction effects of fluoridation, we quantified its health benefits using standardised dental indexes, and we calculated financial savings from averted treatment. We analysed NZ water supplies to estimate the financial costs of fluoridation. We devised a method to represent dental caries experience in quality-adjusted life years.

Results

Over 20 years, the net discounted saving from adding fluoride to reticulated water supplies supplying populations over 500 would be NZ$1401 million, a nine times pay-off. Between 8800 and 13,700 quality-adjusted life years would be gained. While fluoridating reticulated water supplies for large communities is cost-effective, it is unlikely to be so with populations smaller than 500.

Conclusions

Community water fluoridation remains highly cost-effective for all but very small communities. The health benefits—while (on average) small per person—add up to a substantial reduction in the national disease burden across all ethnic and socioeconomic groups.

http://ift.tt/2ABSS7G

Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat: Insights into underlying mechanisms

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Tourandokht Baluchnejadmojarad, Hossein Zeinali, Mehrdad Roghani
Inflammation is a common hallmark of neurodegenerative disorders. Systemic inflammation is usually associated with cognitive deficits. Scutellarin is a flavone with established antioxidant, anti-inflammatory, and neuroprotective effects. In this study, the effect of this flavone in prevention of lipopolysaccharide (LPS)-induced cognitive deficit was evaluated. LPS was i.p. injected at a dose of 500μg/kg/day and scutellarin was administered i.p. at doses of 5, 25, or 50mg/kg/day. Treatment of LPS-injected rats with scutellarin dose-dependently ameliorated deficits of spatial recognition memory in Y maze, discrimination index in novel object discrimination task, and retention and recall index in passive avoidance test. Additionally, scutellarin lowered hippocampal malondialdehyde (MDA) and potentiated antioxidant defense elements comprising superoxide dismutase (SOD), catalase, and glutathione (GSH) in addition to reduction of acetylcholinesterase (AChE) activity. Furthermore, scutellarin decreased hippocampal nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and elevated nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Inappropriate alterations of authophagy markers including beclin-1, LC3 II, mTOR, and P62 were also prevented in the presence of scutellarin. Our findings demonstrate that scutellarin alleviates LPS-induced cognitive disturbances, however, the precise mechanism remains still speculative.



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Characteristics of the trace elements and arsenic, iodine and bromine species in snow in east-central China

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Yunchuan Gao, Chao Yang, Jin Ma, Meixue Yin
Fifty-five snow samples were collected from 11 cities in east-central China. These sampling sites cover the areas with the most snowfall in 2014, there were only two snowfalls from June 2013 to May 2014 in east-central China. Twenty-three trace elements in the filtered snow samples were measured with inductively coupled plasma-mass spectrometry (ICP-MS). Statistical analysis of the results show that the total concentrations of elements in the samples from different cities are in the order of SJZ > LZ > XA > ZZ > GD > NJ > QD > JX > WH > HZ > LA, which are closely related to the levels of AQI, PM2.5 and PM10 in these cities, and their correlation coefficients are 0.93, 0.76 and 0.93. The concentration of elements in snow samples is highly correlated with air pollution and reflects the magnitude of the local atmospheric deposition. The concentrations of Fe, Al, Zn, Ba, and P are over 10.0 μg/L, the concentrations of Mn, Cu, Pb, As, Br and I are between 1.0 μg/L to 10.0 μg/L, the concentrations of V, Cr, Co, Ni, Se, Mo, Cd and Sb are less than 1.0 μg/L in snow samples in east-central China, and Rh, Pd, Pt, Hg were not detected. Iodine and bromine species in all samples and arsenic species (As(III), As(V), dimethylarsinic acid (DMA) and monomethyl arsenic (MMA)) in some samples were separated and measured successfully by HPLC-ICP-MS. The majority of arsenic in the snow samples is inorganic arsenic, and the concentration of As(III) (0.104–1.400 μg/L) is higher than that of As(V) (0.012–0.180 μg/L), while methyl arsenicals, such as DMA and MMA, were almost not detected. The concentration of I⁻ (Br⁻) is much higher than that of IO3⁻ (BrO3⁻). The mean concentration of soluble organic iodine (SOI) (1.64 μg/L) is higher than that of I⁻ (1.27 μg/L), however the concentration of Br⁻ (5.58 μg/L) is higher than that of soluble organic bromine (SOBr) (2.90 μg/L). The data presented here shows that SOI is the most abundant species and the majority of the total bromine is bromide in snow sampled at east-central China. Using Fe as the reference element to calculate the EFs, the enrichment factors of V, Cr, Co, Ni, Mn, Ba and P are between 12.3 and 82.8, and the enrichment factors of Cu, Pb, Mo, Zn, Cd, As, Sb, Br, I and Se are between 189.4 and 27667.9, indicating that these elements are contributed by artificial sources. Results of principal component analysis (PCA) on the elements showed that most of trace elements (e.g. V, Cr, Mn, Co, Ni, Cu, As, Mo, Sb, Se, Br, I, Ba and P)were from the combustion of fossil fuels, traffic and ocean sources and some other elements (e.g. Zn, Cd and Pb) were mainly originated from industrial activities.



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Variations of radon concentration in the atmosphere. Gamma dose rate

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): D.E. Tchorz-Trzeciakiewicz, A.T. Solecki
The purposes of research were following: observation and interpretation of variations of radon concentration in the atmosphere - vertical, seasonal, spatial and analysis of relation between average annual radon concentration and ground natural radiation and gamma dose rate. Moreover we wanted to check the occurrence of radon density currents and the possibility of radon accumulation at the foot of the spoil tip.The surveys were carried out in Okrzeszyn (SW Poland) in the area of the spoil tip formed during uranium mining that took place in 60's of 20th century. The measurements were carried out in 20 measurements points at three heights: 0.2 m, 1 m and 2 m a.g.l. using SSNTD LR-115. The survey lasted one year and detectors were exchanged at the beginning of every season. Uranium eU (ppm), thorium eTh (ppm) and potassium K (%) contents were measured using gamma ray spectrometer Exploranium RS-230, ambient gamma dose rate using radiometer RK-100.The average radon concentration on this area was 52.8 Bq m-3. The highest radon concentrations were noted during autumn and the lowest during winter. We observed vertical variations of radon concentration. Radon concentrations decreased with increase of height above ground level. The decrease of radon with increase of height a.g.l. had logarithmic character. Spatial variations of radon concentrations did not indicate the occurrence of radon density currents and accumulation of radon at the foot of the spoil tip.The analysis of relation between average radon concentrations and ground natural radiation (uranium and thorium content) or gamma dose rate revealed positive relation between those parameters. On the base of results mentioned above we suggested that gamma spectrometry measurements or even cheaper and simpler ambient gamma dose rate measurements can be a useful tool in determining radon prone areas. This should be confirmed by additional research.



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Editorial Board/Aims and Scope

Publication date: 15 December 2017
Source:Vaccine, Volume 35, Issue 50





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Dengue vaccine supplies under endemic and epidemic conditions in three dengue-endemic countries: Colombia, Thailand, and Vietnam

Publication date: 15 December 2017
Source:Vaccine, Volume 35, Issue 50
Author(s): Jung-Seok Lee, Jacqueline K. Lim, Duc Anh Dang, Thi Hien Anh Nguyen, Andrew Farlow
BackgroundDengue fever has been a major public health concern in Colombia, Thailand, and Vietnam. Unlike other infectious diseases, dengue vaccines had not been available for a long time, causing difficulties to control the disease. However, the first live attenuated, tetravalent dengue vaccine (CYD-TDV) became available in 2016 and has been already licensed in some dengue-endemic countries. Because several second-generation dengue vaccines are also in the pipeline, it is critical to understand the efficient allocation of dengue vaccines considering the geographical variation of the disease.MethodsThe Climate Risk Factor (CRF) index was created using the climate and non-climate factors in the three countries. A random-coefficient negative binomial model was chosen to validate the relationship between the CRF index and dengue incidence proxy. Given the statistical significance of the CRF index, high risk areas for dengue fever were identified at the 5 km by 5 km resolution and used to estimate vaccination coverage rates and the number of doses required for various types of vaccination scenarios by country.Results and conclusionsBased upon a three-dose scheme, the estimated number of vaccines required for routine vaccination targeting 9 years old ranged from 1 to 2.6 million doses across the countries during the first year of introduction. A one-off catch-up campaign targeting the age group of 10–17 year olds would require 8 to 18 million additional doses. Routine vaccination (with or without a catch-up campaign) covered 63%, 90%, and 91% of the targeted age group populations in Colombia, Thailand, and Vietnam respectively. Given that many dengue-endemic countries face limited resources and that the costs for mass vaccination campaigns may not be trivial, the findings of this study can guide the decision makers in the three countries regarding the efficient distribution of vaccines by identifying populations at high risk at 5 km by 5 km resolution.



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Accelerating Early Access to Immunotherapies for Advanced Urothelial Carcinoma

http://ift.tt/2zKLYNB

miR-126-5p promotes retinal endothelial cell survival through SetD5 regulatio in neurons [RESEARCH ARTICLE]

Villain Gaëlle, Poissonnier Loïc, Noueihed Baraa, Bonfils Gaëlle, Rivera Jose Carlos, Chemtob Sylvain, Soncin Fabrice, and Mattot Virginie

MicroRNAs are key regulators of angiogenesis, as illustrated by the vascular defects observed in miR-126-deficient animals. While the miR-126 duplex gives rise to two mature microRNAs (miR-126-3p and -5p), these defects were attributed to the loss of miR-126-3p while the role of miR-126-5p during normal angiogenesis in vivo remains unknown. Here, we show that miR-126-5p is expressed in endothelial but also by retinal ganglion cells (RGC) of the postnatal retina and participates in protecting endothelial cells from apoptosis during the establishment of the retinal vasculature. miR-126-5p negatively controls class-3 Semaphorin protein (Sema3A) in RGC through the repression of SetD5, an uncharacterized member of the methyltransferase family of proteins. In vitro, SetD5 controls Sema3A expression independently of its SET domain and co-immunoprecipitates with BRD2, a bromodomain protein which recruits transcription regulators onto the chromatin. Both SetD5 and BRD2 bind to the transcription start site and to upstream promoter regions of the Sema3A locus and BRD2 is necessary for the regulation of Sema3A expression by SetD5.

Thus, neuron-expressed miR-126-5p regulates angiogenesis by protecting endothelial cells of the developing retinal vasculature from apoptosis.

http://ift.tt/2hWvAy2

Zebrafish nanog is primarily required in extraembryonic tissue [RESEARCH ARTICLE]

James A. Gagnon, Kamal Obbad, and Alexander F. Schier

The role of the zebrafish transcription factor Nanog has been controversial. It has been suggested that Nanog is primarily required for the proper formation of the extraembryonic yolk syncytial layer (YSL) and only indirectly regulates gene expression in embryonic cells. In an alternative scenario, Nanog has been proposed to directly regulate transcription in embryonic cells during zygotic genome activation. To clarify the roles of Nanog, we performed a detailed analysis of zebrafish nanog mutants. While zygotic nanog mutants survive to adulthood, maternal-zygotic and maternal mutants exhibit developmental arrest at the blastula stage. In the absence of Nanog, YSL formation and epiboly are abnormal, embryonic tissue detaches from the yolk, and the expression of dozens of YSL and embryonic genes is reduced. Epiboly defects can be rescued by generating chimeric embryos of MZnanog embryonic tissue with wild-type vegetal tissue that includes the YSL and yolk cell. Notably, cells lacking Nanog readily respond to Nodal signals and when transplanted into wild-type hosts proliferate and contribute to embryonic tissues and adult organs from all germ layers. These results indicate that zebrafish Nanog is necessary for proper YSL development but is not directly required for embryonic cell differentiation.

http://ift.tt/2jqCCeX

The ATPase activity of Asna1/TRC40 is required for pancreatic progenitor cell survival [RESEARCH ARTICLE]

Stefan Norlin, Vishal Parekh, and Helena Edlund

Asna1, also known as TRC40, is implicated in delivery of tail anchored (TA) proteins into the ER, in vesicle-mediated transport, and in chaperoning unfolded proteins during oxidative stress/ATP depletion. We recently showed that Asna1 inactivation in β-cells resulted in impaired retrograde transport, ER stress and diabetes in mice. Here we show that Asna1 inactivation in pancreatic progenitor cells leads to redistribution of the Golgi TA SNAREs Syntaxin-5 and Syntaxin-6, Golgi fragmentation, and accumulation of cytosolic p62⁺ puncta. Asna1^–/– multipotent progenitor cells (MPCs) selectively activate integrated stress response signalling and undergo apoptosis, thereby disrupting endocrine and acinar cell differentiation, resulting in pancreatic agenesis. Rescue experiments implicate the Asna1 ATPase activity and CXXC di-cysteine motif in ensuring Golgi integrity, Syntaxin-5 localization and MPC survival. Ex vivo inhibition of retrograde transport reproduces the perturbed Golgi morphology and Syntaxin-5 and Syntaxin-6 expression, whereas modulation of p53 activity using PFT-α and Nutlin-3, prevents or reproduces apoptosis in Asna1 deficient and wildtype MPCs, respectively. These findings support a role for the Asna1 ATPase activity in ensuring survival of pancreatic MPCs, possibly by counteracting p53 mediated apoptosis.

http://ift.tt/2hWvtT8

Plasticity within the niche ensures the maintenance of a Sox2+ stem cell population in the mouse incisor [RESEARCH ARTICLE]

Maria Sanz-Navarro, Kerstin Seidel, Zhao Sun, Ludivine Bertonnier-Brouty, Brad A. Amendt, Ophir D. Klein, and Frederic Michon

In mice, the incisors grow throughout the animal's life, and this continuous renewal is driven by dental epithelial and mesenchymal stem cells. Sox2 is a principal marker of the epithelial stem cells that reside in the mouse incisor stem cell niche, called the labial cervical loop, but relatively little is known about the role of the Sox2+ stem cell population. In this study, we show that conditional deletion of Sox2 in the embryonic incisor epithelium leads to growth defects and impairment of ameloblast lineage commitment. Deletion of Sox2 specifically in Sox2+ cells during incisor renewal revealed cellular plasticity that leads to the relatively rapid restoration of a Sox2-expressing cell population. Furthermore, we show that Lgr5-expressing cells are a subpopulation of dental Sox2+ cells that also arise from Sox2+ cells during tooth formation. Finally, we show that the embryonic and adult Sox2+ populations are regulated by distinct signaling pathways, which is reflected in their distinct transcriptomic signatures. Together, our findings demonstrate the heterogeneity of the Sox2+ population and reinforce its importance for incisor homeostasis.

http://ift.tt/2jqBMij

Perturbation of canonical and non-canonical BMP signaling affects migration, polarity and dendritogenesis of mouse cortical neurons [RESEARCH ARTICLE]

Monika Saxena, Nitin Agnihotri, and Jonaki Sen

Bone Morphogenetic Protein (BMP) signaling has been implicated in regulation of patterning of the forebrain and as a regulator of neurogenesis and gliogenesis in the mammalian cortex. However, its role in regulating other aspects of cortical development in vivo remains unexplored. We hypothesized that BMP signaling may regulate additional processes during the development of cortical neurons after observing the presence of active BMP signaling in a spatio-temporally dynamic pattern in the mouse cortex. Our investigation revealed that BMP signaling specifically regulates migration, polarity and the dendritic morphology of upper layer cortical neurons born at E15.5. On further dissection of the role of canonical and non-canonical BMP signaling in each of these processes, we found that migration of these neurons is regulated by both canonical and non-canonical BMP signaling. Their polarity however appears to be affected more strongly by canonical BMP signaling while dendritic branch formation appears to be somewhat more strongly affected by LIMK-mediated non-canonical BMP signaling.

http://ift.tt/2hWvl66

The skeletal phenotype of Achondrogenesis type 1A is caused exclusively by cartilage defects [RESEARCH ARTICLE]

Ian M. Bird, Susie H. Kim, Devin K. Schweppe, Joana Caetano-Lopes, Alexander G. Robling, Julia F. Charles, Steven P. Gygi, Matthew L. Warman, and Patrick J. Smits

Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by Trip11) cause Achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development is also abnormal, but since chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of the cartilage defect. A possible explanation for the tissue specificity of ACG1A is that cartilage and bone are highly secretory tissues with a high usage of the membrane trafficking machinery. The perinatal lethality of ACG1A prevented investigating this hypothesis. We therefore generated mice with conditional Trip11 knockout alleles, and inactivated Trip11 in chondrocytes, osteoblasts, osteoclasts and pancreas acinar cells, all highly secretory cell types. We discovered that the ACG1A skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When we inactivated Trip11 in primary chondrocyte cultures, GMAP-210 deficiency affected trafficking of a subset of chondrocyte-expressed proteins rather than globally impairing membrane trafficking. Thus, GMAP-210 is essential for trafficking specific cargoes in chondrocytes but is dispensable in other highly secretory cells.

http://ift.tt/2jqZrz0

Maternal Nanog is critical for the zebrafish embryo architecture and for cell viability during gastrulation [RESEARCH ARTICLE]

Marina Veil, Melanie Anna Schaechtle, Meijiang Gao, Viola Kirner, Lenka Buryanova, Rachel Grethen, and Daria Onichtchouk

Nanog has been implicated in establishment of pluripotency in mammals and in zygotic genome activation in zebrafish. In this study we characterize the development of maternal and zygotic MZnanog null mutant zebrafish embryos. Without functional Nanog, epiboly is severely affected, embryo axes do not form and massive cell death starts at the end of gastrulation. We show that three independent defects in MZnanog mutants contribute to epiboly failure: yolk microtubule organization required for epiboly is abnormal, maternal mRNA fails to degrade due to the absence of miR-430 and actin structure of the yolk syncytial layer does not form properly. We further demonstrate that the cell death in MZnanog embryos is cell-autonomous. Nanog is necessary for correct spatial expression of the ventral specifying genes bmp2b, vox, and vent, and neural transcription factor her3. It is also required for the correctly timed activation of endoderm genes and for the degradation of maternal eomesa mRNA via miR-430. Our findings suggest that maternal Nanog coordinates several gene regulatory networks that shape the embryo during gastrulation.

http://ift.tt/2hWveYe

Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]

Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai

Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1^Limb/Limb) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1^Limb/Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1, which is reported to be an IL-1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation such as Mmp13. These results indicate that Uhrf1 governs cell-type specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.

http://ift.tt/2jr9SCM

Cell-Autonomous Metabolic Reprogramming in Hypoxia

Publication date: Available online 27 November 2017
Source:Trends in Cell Biology
Author(s): Luana Schito, Sergio Rey
Molecular oxygen (O2) is a universal electron acceptor that enables ATP synthesis through mitochondrial respiration in all metazoans. Consequently, hypoxia (low O2) has arisen as an organizing principle for cellular evolution, metabolism, and (patho)biology, eliciting a remarkable panoply of metabolic adaptations that trigger transcriptional, translational, post-translational, and epigenetic responses to determine cellular fitness. In this review we summarize current and emerging cell-autonomous molecular mechanisms that induce hypoxic metabolic reprogramming in health and disease.



http://ift.tt/2BvqUI6

Heterotypic Ubiquitin Chains: Seeing is Believing

Publication date: Available online 27 November 2017
Source:Trends in Cell Biology
Author(s): Alexandra Stolz, Ivan Dikic
The biological diversity of ubiquitination resides in the multivalent nature of linkage-specific homotypic and heterotypic ubiquitin (Ub) chains. A recent publication by Yau et al. in Cell describes the development of K11/K48-bispecific antibodies and a physiological role for K11/K48 heterotypic chains in regulation of the cell cycle and clearance of aggregated proteins.



http://ift.tt/2zvqGiR

The Walking Dead: sequential nuclear and organelle destruction during hair development

Abstract

Background

Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm, is key to hair production. This form of cell "death", or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms specifically in the hair follicle.

Objectives

To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology.

Methods

Scalp biopsies and hair pluck samples were obtained from healthy human donors and analysed microscopically following immunohistochemical staining.

Results

A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft that also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependant and -independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe.

Conclusions

We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of ROS required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining "living" characteristic thus completing the march from "living" to "dead" within the hair follicle.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ibx8I7

The Walking Dead: sequential nuclear and organelle destruction during hair development

Abstract

Background

Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm, is key to hair production. This form of cell "death", or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms specifically in the hair follicle.

Objectives

To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology.

Methods

Scalp biopsies and hair pluck samples were obtained from healthy human donors and analysed microscopically following immunohistochemical staining.

Results

A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft that also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependant and -independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe.

Conclusions

We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of ROS required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining "living" characteristic thus completing the march from "living" to "dead" within the hair follicle.

This article is protected by copyright. All rights reserved.

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Comparative efficacy of endodontic medicaments & sodium hypochlorite against Enterococcus faecalis biofilms

Abstract

Background

Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim was to compare the efficacy of commonly used medicaments against Enterococcus faecalis cultured as a biofilm on dentine substrate.

Method

An E. faecalis biofilm was established on human dentine slices using a continuous flow cell. Each test medicament (Ledermix, Ca(OH)₂, Odontoposte, 0.2% chlorohexidine and 50:50 combinations of Ledermix/Ca(OH)₂ and Odontopaste/ Ca(OH)₂) was introduced into the flow cell and biofilms were harvested and quantitated by determining cellular protein. Cellular viability was determined using serial plating and the number of colony forming units was normalised against cellular protein to allow treatment protocols to be compared. Qualitative SEM analyses of the biofilm were done after a 48-hour exposure to each test agent.

Results

Sodium hypochlorite achieved total bacterial elimination. Ledermix and Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH)₂ and 50:50 combinations of Ca(OH)₂ /Ledermix or Ca(OH)₂/Odontopaste reduced the viability by > 99% while 0.2% chlorhexidine reduced bacterial numbers by 97%.

Conclusion

Sodium hypochlorite remains the gold standard for bacterial elimination in root canal therapy. However, Ca(OH)₂ in isolation and combined with Ledermix, and Odontopaste was highly effective in reducing bacterial viability.

This article is protected by copyright. All rights reserved.

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MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Shipin Zhang, Shang Jiunn Chuah, Ruenn Chai Lai, James Hoi Po Hui, Sai Kiang Lim, Wei Seong Toh
Mesenchymal stem cell (MSC) exosome was previously shown to be effective in repairing critical size osteochondral defects in an immunocompetent rat model. Here we investigate the cellular processes modulated by MSC exosomes and the mechanism of action underlying the exosome-mediated responses in cartilage repair. We observed that exosome-mediated repair of osteochondral defects was characterised by increased cellular proliferation and infiltration, enhanced matrix synthesis and a regenerative immune phenotype. Using chondrocyte cultures, we could attribute the rapid cellular proliferation and infiltration during exosome-mediated cartilage repair to exosomal CD73-mediated adenosine activation of AKT and ERK signalling. Inhibitors of AKT or ERK phosphorylation suppressed exosome-mediated increase in cell proliferation and migration but not matrix synthesis. The role of exosomal CD73 was confirmed by the attenuation of AKT and ERK signalling by AMPCP, a CD73 inhibitor and theophylline, an adenosine receptor antagonist. Exosome-treated defects also displayed a regenerative immune phenotype characterised by a higher infiltration of CD163⁺ regenerative M2 macrophages over CD86⁺ M1 macrophages, with a concomitant reduction in pro-inflammatory synovial cytokines IL-1β and TNF-α. Together, these observations demonstrated that the efficient osteochondral regeneration by MSC exosomes was effected through a coordinated mobilisation of multiple cell types and activation of several cellular processes.



http://ift.tt/2AzSzdA

Rerouting mesenchymal stem cell trajectory towards epithelial lineage by engineering cellular niche

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Ananya Barui, Farhan Chowdhury, Abhay Pandit, Pallab Datta
Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subsequent investigations showed differentiation potential into other cell types of mesoderm origin including osteoblasts, adipocytes, fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and endodermal cells, phenomena referred to as 'stem cell plasticity'. This opened the possibility of clinical applications of MSCs in the regeneration of other tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal regeneration, homing of MSCs for regeneration at sites of injury etc. Though several evidence have accrued demonstrating this phenomenon, there is still a gap in understanding the molecular mechanism of such transitions which will be important to efficiently control the process. Interestingly, the process can be drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes place inside the body during embryonic development or certain pathophysiological conditions. In this review, a brief attempt is first made to understand the evidence of MSC transdifferentiation based on the current knowledge about MET. We then specifically focus on systematic presentation and analysis of the microenvironment factors involved in MSC transdifferentiation to epithelial lineages which would have applications in regenerative medicine.



http://ift.tt/2icyNgT

Crosstalk between developing vasculature and optogenetically engineered skeletal muscle improves muscle contraction and angiogenesis

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Tatsuya Osaki, Vivek Sivathanu, Roger D. Kamm
Capillary networks surrounding skeletal muscle play an important role in not only supplying oxygen and nutrients but also in regulating the myogenesis and repair of skeletal muscle tissues. Herein, we model the early stages of 3D vascularized muscle fiber formation in vitro using a sequential molding technique to investigate interactions between angiogenesis of endothelial cells and myogenesis of skeletal muscle cells. Channelrhodopsin-2 C2C12 muscle fiber bundles and 3D vascular structures (600 μm diameter) were formed at 500 μm intervals in a collagen gel. Endothelial cells exhibited an emergent angiogenic sprouting behavior over several days, which was modulated by the muscle fiber bundle through the secretion of angiopoietin-1. Through a reciprocal response, myogenesis was also upregulated by interactions with the vascular cells, improving muscle contraction via angiopoetin-1/neuregulin-1 signaling. Moreover, continuous training of muscle tissue by optical stimulation induced significantly more angiogenic sprouting. This in vitro model could be used to better understand the formation of vascularized muscle tissues and to test the interactions between muscle growth, repair or training and angiogenesis for applications in tissue engineering and regenerative medicine.



http://ift.tt/2Aav5Lr

A gapmer aptamer nanobiosensor for real-time monitoring of transcription and translation in single cells

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Shue Wang, Yuan Xiao, Donna D. Zhang, Pak Kin Wong
Transcription and translation are under tight spatiotemporal regulation among cells to coordinate multicellular organization. Methods that allow massively parallel detection of gene expression dynamics at the single cell level are required for elucidating the complex regulatory mechanisms. Here we present a multiplex nanobiosensor for real-time monitoring of protein and mRNA expression dynamics in live cells based on gapmer aptamers and complementary locked nucleic acid probes. Using the multiplex nanobiosensor, we quantified spatiotemporal dynamics of vascular endothelial growth factor A mRNA and protein expressions in single human endothelial cells during microvascular self-organization. Our results revealed distinct gene regulatory processes in the heterogeneous cell subpopulations.



http://ift.tt/2ibILis

Structure-based design for binding peptides in anti-cancer therapy

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Sheng-Hung Wang, John Yu
The conventional anticancer therapeutics usually lack cancer specificity, leading to damage of normal tissues that patients find hard to tolerate. Ideally, anticancer therapeutics carrying payloads of drugs equipped with cancer targeting peptides can act like "guided missiles" with the capacity of targeted delivery toward many types of cancers. Peptides are amenable for conjugation to nano drugs for functionalization, thereby improving drug delivery and cellular uptake in cancer-targeting therapies. Peptide drugs are often more difficult to design through molecular docking and in silico analysis than small molecules, because peptide structures are more flexible, possess intricate molecular conformations, and undergo complex interactions. In this review, the development and application of strategies for structure-based design of cancer-targeting peptides against GRP78 are discussed. This Review also covers topics related to peptide pharmacokinetics and targeting delivery, including molecular docking studies, features that provide advantages for in vivo use, and properties that influence the cancer-targeting ability. Some advanced technologies and special peptides that can overcome the pharmacokinetic challenges have also been included.

Graphical abstract

http://ift.tt/2AzGTb0

Targeted drug delivery for tumor therapy inside the bone marrow

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Chao-Feng Mu, Jianliang Shen, Jing Liang, Hang-Sheng Zheng, Yang Xiong, Ying-Hui Wei, Fanzhu Li
Bone marrow is the primary hematopoietic organ, which is involved in multiple malignant diseases including acute and chronic leukemia, multiple myeloma, myelodysplastic syndromes, and bone metastases from solid tumors. These malignancies affect normal homeostasis and reshape the bone marrow microenvironment. There are limited treatment options for them because of their inevitable aggravation. The current systemic administration of anticancer agents is difficult to achieve ideal therapeutic dose to suppress tumor growth at bone marrow diseased sites, and is always associated with a high incidence of relapse and severe side effects. The limitations of current treatments urge scientists to develop bone marrow targeted drug delivery systems intended for the treatment of diseased bone marrow, which can improve the efficacy of therapeutic agents and reduce their dose-limiting systemic side effects on healthy tissues. In this review we first present the current opinions on bone marrow vasculature, as well as the molecular and structural interactions between tumor cells and the diseased bone marrow. In the second part, we highlight the different design rationales and strategies of bone marrow delivery systems and their therapeutic applications for the treatment of malignancies inside the bone marrow.

Graphical abstract

http://ift.tt/2Azo4Ex

Are Meta-Analyses a Form of Medical Fake News?: Thoughts About How They Should Contribute to Medical Science and Practice.

Author: Packer, Milton MD

Page: 2097-2099

http://ift.tt/2ibC7ZB

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

Author: Baumgartner, Christine MD; da Costa, Bruno R. MSc, PhD; Collet, Tinh-Hai MD; Feller, Martin MD, MSc; Floriani, Carmen MD; Bauer, Douglas C. MD; Cappola, Anne R. MD, ScM; Heckbert, Susan R. MD, PhD; Ceresini, Graziano MD, PhD; Gussekloo, Jacobijn MD, PhD; den Elzen, Wendy P.J. PhD; Peeters, Robin P. MD, PhD; Luben, Robert BSc; Volzke, Henry MD; Dorr, Marcus MD; Walsh, John P. MBBS, PhD; Bremner, Alexandra PhD; Iacoviello, Massimo MD, PhD; Macfarlane, Peter DSc, Efesc; Heeringa, Jan MD, PhD; Stott, David J. MD, PhD; Westendorp, Rudi G. J. MD, PhD; Khaw, Kay-Tee MD; Magnani, Jared W. MD, MSc; Aujesky, Drahomir MD, MSc; Rodondi, Nicolas MD, MAS; for the Thyroid Studies Collaboration

Page: 2100-2116

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Mild Thyroid Dysfunction: A Potential Target in Prevention of Atrial Fibrillation?.

Author: Selmer, Christian MD, PhD; Faber, Jens MD, DMSc

Page: 2117-2118

http://ift.tt/2ibC3ZR

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

Author: Kudenchuk, Peter J. MD; Leroux, Brian G. PhD; Daya, Mohamud MD, MS; Rea, Thomas MD, MPH; Vaillancourt, Christian MD, MSc; Morrison, Laurie J. MD, MSc; Callaway, Clifton W. MD, PhD; Christenson, James MD; Ornato, Joseph P. MD; Dunford, James V. MD; Wittwer, Lynn MD, MS; Weisfeldt, Myron L. MD; Aufderheide, Tom P. MD, MS; Vilke, Gary M. MD; Idris, Ahamed H. MD; Stiell, Ian G. MD, MSc; Colella, M. Riccardo DO, MPH; Kayea, Tami LP, MS; Egan, Debra MSc, MPH; Desvigne-Nickens, Patrice MD; Gray, Pamela NREMT-P; Gray, Randal Med, NREMT-P; Straight, Ron MEd; Dorian, Paul MD, MSc; Resuscitation Outcomes Consortium Investigators

Page: 2119-2131

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Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement: Insights from the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

Author: Hyman, Matthew C. MD, PhD; Vemulapalli, Sreekanth MD; Szeto, Wilson Y. MD; Stebbins, Amanda MS; Patel, Prakash A. MD; Matsouaka, Roland A. PhD; Herrmann, Howard C. MD; Anwaruddin, Saif MD; Kobayashi, Taisei MD; Desai, Nimesh D. MD, PhD; Vallabhajosyula, Prashanth MD; McCarthy, Fenton H. MD, MS; Li, Robert MD; Bavaria, Joseph E. MD; Giri, Jay MD, MPH

Page: 2132-2140

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Is Less Really More?: Conscious Sedation or General Anesthesia for Transcatheter Aortic Valve Replacement.

Author: Brown, Charles H. IV MD, MHS; Hasan, Rani K. MD, MHS; Brady, Mary Beth MD

Page: 2141-2143

http://ift.tt/2Ac4ihT

Metabolism: A Direct Link Between Cardiac Structure and Function.

Author: Brookes, Paul S. PhD; Taegtmeyer, Heinrich MD, DPhil

Page: 2158-2161

http://ift.tt/2Ac4hdP

C1q/Tumor Necrosis Factor-Related Protein-9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways.

Author: Yan, Wenjun MD, PhD *,,; Guo, Yongzhen BS *,; Tao, Ling MD, PhD; Lau, Wayne Bond MD; Gan, Lu PhD; Yan, Zheyi MD; Guo, Rui PhD; Gao, Erhe MD, PhD; Wong, G. William MD, PhD; Koch, Walter L. PhD; Wang, Yajing MD, PhD; Ma, Xin-Liang MD, PhD

Page: 2162-2177

http://ift.tt/2ibBRK7

Handheld Echocardiography: Current State and Future Perspectives.

Author: Chamsi-Pasha, Mohammed A. MD; Sengupta, Partho P. MD, DM; Zoghbi, William A. MD, MACC

Page: 2178-2188

http://ift.tt/2Ac4gGN

Highlights From the Circulation Family of Journals.

Author:

Page: 2189-2194

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Impact of Coronary Computed Tomography Angiography Findings on Initiation of Cardioprotective Medications.

Author: Chang, Anna Marie MD, MSCE; Litt, Harold I. MD, PhD; Snyder, Bradley S. MS; Gatsonis, Constantine PhD; Greco, Erin M. MS; Miller, Chadwick D. MD, MS; Singh, Harjit MD; O'Conor, Katie J. BS; Hollander, Judd E. MD

Page: 2195-2197

http://ift.tt/2Ac4cqx

Breast MRI as a Problem-solving Study in the Evaluation of BI-RADS Categories 3 and 4 Microcalcifications

Publication date: Available online 27 November 2017
Source:Academic Radiology
Author(s): Akiko Shimauchi, Youichi Machida, Ichiro Maeda, Eisuke Fukuma, Kazuei Hoshi, Mitsuhiro Tozaki
Rationale and ObjectivesWe aimed to investigate the utility of problem-solving breast magnetic resonance imaging (MRI) for mammographic Breast Imaging Reporting and Data System (BI-RADS) categories 3 and 4 microcalcifications.Materials and MethodsBetween January 1, 2010 and December 31, 2011, 138 women with 146 areas of categories 3 and 4 microcalcifications without sonographic correlates underwent breast MRI and had a stereotactic core biopsy using an 11-gauge needle or follow-up at least for 24 months. Positive predictive value (PPV), negative predictive value, sensitivity, and specificity were calculated on the basis of BI-RADS category, with categories 1–3 being considered benign and categories 4 and 5 being considered malignant.ResultsTwenty-four cases (16.4%) were malignant (18 ductal carcinoma in situ, 6 invasive). MRI increased PPV and specificity from 43% to 68% and from 80% to 93% (P = .054 and .005) compared to mammography. Within 102 category 3 microcalcifications, 5 carcinomas were assessed correctly as category 4 by MRI. Within 44 category 4 microcalcifications, a correct diagnosis was made by MRI in 77% (34 of 44) as opposed to 43% (19 of 44) by mammography, and 80% (20 of 25) of unnecessary biopsies could have been avoided. Within the 24 carcinomas, 5 were negative at MRI. MRI-negative carcinomas have a significantly higher possibility of being low grade (ductal carcinoma in situ or invasive) (P = .0362).ConclusionsBreast MRI has the potential to improve the diagnosis of category 3 or 4 microcalcifications and could alter indications for biopsy. Breast MRI could help predict the presence or absence of higher-grade carcinoma for category 3 or 4 microcalcifications.



http://ift.tt/2n6T0Gm

Model-based Iterative Reconstruction in Low-radiation-dose Computed Tomography Colonography

Publication date: Available online 27 November 2017
Source:Academic Radiology
Author(s): Narumi Taguchi, Seitaro Oda, Masanori Imuta, Sadahiro Yamamura, Takeshi Nakaura, Daisuke Utsunomiya, Masafumi Kidoh, Yasunori Nagayama, Hideaki Yuki, Kenichiro Hirata, Yuji Iyama, Yoshinori Funama, Hideo Baba, Yasuyuki Yamashita
Rationale and ObjectivesTo assess the effect of model-based iterative reconstruction (MBIR) on image quality and diagnostic performance of low-radiation-dose computed tomography colonography (CTC) in the preoperative assessment of colorectal cancer.Materials and MethodsThis study included 30 patients with colorectal cancer referred for surgical treatment. All patients underwent CTC with a standard dose (SD) protocol in the supine position and a low-dose (LD; radiation dose reduction of approximately 85%) protocol in the prone position. The SD protocol images were post-processed using filtered back projection (FBP), whereas the LD protocol images were post-processed using FBP and MBIR. Objective and subjective image quality parameters were compared among the three different methods. Preoperative evaluations, including site, length, and tumor and node staging were performed, and the findings were compared to the postsurgical findings.ResultsThe mean image noise of SD-FBP, LD-FBP, and LD-MBIR images was 17.3 ± 3.2, 40.5 ± 10.9, and 11.2 ± 2.0 Hounsfield units, respectively. There were significant differences for all comparison combinations among the three methods (P < .01). For image noise, the mean visual scores were significantly higher for SD-FBP and LD-MBIR than for LD-FBP, and the scores for SD-FBP and LD-MBIR were equivalent (3.9 ± 0.3 [SD-FBP], 2.0 ± 0.5 [LD-FBP], and 3.7 ± 0.3 [LD-MBIR]). Preoperative information was more accurate under SD-FBP and LD-MBIR than under LD-FBP, and the information was comparable between SD-FBP and LD-MBIR.ConclusionMBIR can yield significantly improved image quality on low-radiation-dose CTC and provide preoperative information equivalent to that of standard-radiation-dose protocol.



http://ift.tt/2zJtUmT

CT Features of Hepatic Veno-occlusive Disease

Publication date: Available online 27 November 2017
Source:Academic Radiology
Author(s): Song Yang, Jing Wu, Si Lei
Rationale and ObjectiveThe computed tomography (CT) features of hepatic veno-occlusive disease (HVOD) could play a role in its diagnosis. We aimed to perform a meta-analysis of studies examining the CT features of HVOD.MethodsRelevant studies published up to May 3, 2017 were searched in major electronic databases. The extracted data included the proportion of various CT features in patients with HVOD. The meta-analysis was conducted using R 3.3.3 with the "meta" package.ResultsEleven studies were included. The studies involved 326 patients with a mean age range of 50.2–58.9 years, and the proportion of female patients ranged from 20% to 57.5%. The meta-analysis showed the pooled proportion of CT features: hepatic parenchyma with heterogeneous hypoattenuation (81.05%, 95% confidence interval [CI]: 56.97%–93.25%), patchy enhancement in the portal venous phase (87.09%, 95% CI: 75.15%–93.77%) with or without a narrow or invisible hepatic vein (71.02% 95% CI: 42.09%–89.20%), gallbladder wall edema (65.51%, 95% CI: 28.98%–89.84%), and patchy heterogeneous enhancement in the arterial phase (44.36%, 95% CI: 29.98%–59.76%) with or without slightly enlarged hepatic artery (56.61%, 95% CI: 40.62%–71.33%).ConclusionHepatic parenchyma with heterogeneous hypoattenuation and patchy enhancement with or without narrowing or an invisible hepatic vein in the portal venous or equilibrium phase may be the most important CT feature for diagnosing HVOD.



http://ift.tt/2nblbny

The Benefits of Maintaining a Diagnostic and Interventional Co-sponsored Radiology Interest Group

Publication date: Available online 27 November 2017
Source:Academic Radiology
Author(s): Michael V. Friedman, Jennifer E. Gould, Gretchen M. Foltz




http://ift.tt/2zKYBbu

Effect of burn rehabilitation program on improving quality of life (QoL) for hand burns patients: a randomized controlled study

Abstract

Background

Burn injuries, including hands are one of the most devastating injuries. Hand burns do not often play a major role in the mortality. But, they represent a huge problem that may eventually lead to chronic disabilities, lifelong impairment, and significant functional and occupational limitations. These comorbidities can negatively affect a patient's quality of life (QoL) besides, making re-integration into society is difficult. This study aims to investigate the effect of our designated burn rehabilitation program on improving quality of life of hand burns patients.

Methods

A randomized controlled study was conducted for 12 months at Mansoura University Burn Center. It included 60 adult patients with hand burns who were randomly divided and assigned to a study and control groups. Both groups underwent basic rehabilitation. A newly designed program was implemented for the study group. Data were collected using three tools; bio-socio demographic characteristics, the Burn Health Knowledge Questionnaire, and the Burn Specific Health Scale-Brief (BSHS-B). The quality of life of patients with hand burns was evaluated three times.

Results

One month and three months after implementing the burn rehabilitation program, the total mean scores for the QoL of patients in the study group improved from 31.1 ± 11.3 to 118.5 ± 21.3 and 135.4 ± 24.3, respectively (P < 0.001). In addition, the changes in QoL of the patients in the control group significantly improved from 24.8 ± 12.1 to 57.6 ± 19.1 and 87.5 ± 23.8, respectively (P < 0.001). Despite this steady improvement in the control group, the mean scores on the QoL sub-scales and total mean scores remained lower than those in the study group.

Conclusions

Based on the results obtained in the current study, the design and implemention of a burn rehabilitation programme based on clinical knowledge improves the quality of life of patients with burns. Therefore, this program is recommended for use early as a part of the treatment process for patients with burns.

Level of Evidence: Level I, risk/prognostic study.

http://ift.tt/2BhRQtU

Evaluation of the Implantable Doppler Probe for Free Flap Monitoring in Lower Limb Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0037-1608628

Background Timely reexploration and reanastomoses can salvage failing free flaps. The use of the implantable Doppler probe provides direct evidence of vascular impairment of the microvascular anastomoses and allows for postoperative NPWT. The aim of this retrospective study was to compare the Doppler probe to conventional monitoring techniques for free flap monitoring in lower limb reconstruction and to identify risk factors for perfusion disturbance and reexploration. Methods All patients receiving free muscle flap reconstruction for lower limb soft tissue defects at our department from 2000 to 2013 were included, and all adverse events, timely detection of perfusion problems, and outcome of revision surgery were assessed by chart analysis. Results For lower limb reconstruction, 110 free muscle transfers were performed of which 41 muscle flaps were conventionally monitored and 69 flaps were monitored using the implantable Doppler probe. In 18 cases, the free muscle flaps needed revision because of perfusion disturbances. The salvage rate was 80% with monitoring by the implantable Doppler probe compared with 62.5% using conventional monitoring methods resulting in success rates of 95.7 and 92.7%, respectively. Conclusion The use of the implantable Cook–Swartz Doppler probe represents a safe monitoring method for lower limb reconstruction, which allows for the additional use of NPWT. Higher salvage and revision success rates can be attributed to an earlier detection of perfusion impairment. However, a larger patient cohort is necessary to verify superiority over conventional postoperative monitoring.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Staged Reconstruction (Delayed-Immediate) of the Maxillectomy Defect Using CAD/CAM Technology

J reconstr Microsurg
DOI: 10.1055/s-0037-1607394

Background Computer-aided design/computer-aided manufacturing (CAD/CAM) technology has become increasingly popular for free fibula reconstruction of the mandible. The same technology, however, has not been widely utilized in immediate complex midface reconstruction utilizing free fibula flaps. Maxillary defects are difficult to precisely predict or produce matched cutting guides for after the ablative surgery. We present a protocol for "delayed-immediate" two-stage reconstruction for complex mid-facial defects, by delaying lymph node neck dissection and using CAD/CAM technology for delayed bony reconstruction. Methods Stage 1 includes the extirpative surgery, placement of a temporary obturator, and an immediate post-excision fine cut computed tomography (CT) of the defect that is used for CAD/CAM planning. The time interval between stages is used for virtual surgical planning (VSP) and provides an opportunity for the final pathologic margins to be evaluated. At stage 2, definitive reconstruction is performed in conjunction with the delayed neck dissection. Briefly delaying the neck dissection until stage 2 allows for recipient vessel dissection and microsurgical anastomoses to safely occur in a surgically naïve neck. Conclusion A two-stage delayed-immediate reconstruction of complex mid-face defects can be safely and effectively performed. This protocol takes advantage of advancing CAD/CAM technology, provides an opportunity to evaluate final margins, and avoids recipient vessel dissection and microsurgery in previously operated or irradiated necks.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2AbXSiN