Cassiopea jellyfish prove that sleep requires no brain By Armando Ortiz '19 The mechanisms of sleep and its effects on the nervous system continue to baffle scientists with many unanswered questions surrounding this topic. One recent study on primitive jellyfish further adds to scientists' questions about the origin of sleep […]
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Τρίτη 3 Οκτωβρίου 2017
Cassiopea jellyfish prove that sleep requires no brain
A Genetic Explanation for the Process of Aging
A Genetic Explanation for the Process of Aging Sam Neff '21 / Biological Sciences, News, Fall 2017 / September 24, 2017 A recent study from the Institute of Molecular Biology in Mainz, Germany examining the genome of the nematode C. elegans has yielded a significant discovery. Researchers studied certain aging-related […]
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Why Poison Frogs Don’t Poison Themselves
Why Poison Frogs Don't Poison Themselves By Amanda Jiang '21 Summary: Researchers at the University of Texas at Austin have recently discovered how the specific epibatidine toxin receptor interacts with epibatidine through studying its presence in Epipedobates anthonyi frogs. The epibatidine receptor has been found to be in the same […]
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Issue Information
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IL-36 in hidradenitis suppurativa: Evidence for a distinctive pro-inflammatory role and a key factor in the development of an inflammatory loop
Abstract
Background
A possible regulatory involvement of the interleukin (IL)-36 family in inflammatory diseases has been suggested.
Objectives
To analyze the expression of IL-36α, β, γ, and the antagonistic cytokines IL-36Ra, IL-37, and IL38 in the skin of hidradenitis suppurativa (HS) patients.
Methods
Skin samples from lesional and corresponding perilesional HS skin, and from healthy controls were included in this study and analyzed by quantitative real-time RT-PCR. To evaluate the PCR results of IL-36α, β, and γ, a subset of skin samples was studied by immunohistochemistry.
Results
Expression levels of IL-36α, β, γ, and IL-36Ra were all significantly higher in lesional HS skin compared to healthy controls. IL-37 and IL-38 were significantly higher in perilesional HS skin compared to healthy controls and decreased in lesional HS skin.
Limitations
Descriptive study and small sample size.
Conclusions
Our results showed a possible involvement of IL-36 cytokines in the inflammatory network of HS and a dysbalance between the agonistic and antagonistic cytokines in HS skin.
This article is protected by copyright. All rights reserved.
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Systemic retinoids and psychiatric disorders in patients with skin diseases: a multifactorial relationship
Abstract
Le Moigne and colleagues reviewed case reports to examine a possible causal linkage between systemic retinoids and psychiatric disorders.1 The authors conclude that systemic retinoids should be prescribed with vigilance for patients with psychiatric disorders. While we agree with a need for vigilance, we caution against prematurely concluding that there is a causal association.
This article is protected by copyright. All rights reserved.
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Meta-analysis on shift work and risks of specific obesity types
Summary
Aims
This systematic review and meta-analysis evaluated the associations between shift work patterns and risks of specific types of obesity.
Methods
PubMed was searched until March 2017 for observational studies that examined the relationships between shift work patterns and obesity. Odds ratio for obesity was extracted using a fixed-effects or random-effects model. Subgroup meta-analyses were carried out for study design, specific obesity types and characteristics of shift work pattern.
Results
A total of 28 studies were included in this meta-analysis. The overall odds ratio of night shift work was 1.23 (95% confidence interval = 1.17–1.29) for risk of obesity/overweight. Cross-sectional studies showed a higher risk of 1.26 than those with the cohort design (risk ratio = 1.10). Shift workers had a higher frequency of developing abdominal obesity (odds ratio = 1.35) than other obesity types. Permanent night workers demonstrated a 29% higher risk than rotating shift workers (odds ratio 1.43 vs. 1.14).
Conclusion
This meta-analysis confirmed the risks of night shift work for the development of overweight and obesity with a potential gradient association suggested, especially for abdominal obesity. Modification of working schedules is recommended, particularly for prolonged permanent night work. More accurate and detailed measurements on shift work patterns should be conducted in future research.
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Osteitis of the radius following Bacillus Calmette–Guérin vaccination at birth: a case report
The Bacillus Calmette–Guérin vaccine, which is used for the prevention of tuberculosis, is considered protective against the severe forms of childhood tuberculosis. However, some serious adverse reactions incl...
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Time is nothing: emotional consistency of autobiographical memory and its neural basis
Abstract
The emotional aspect of autobiographical memories (AMs) is associated with self-related processing, which plays an important role in mental health. However, the emotional consistency dimension of AMs and its neural underpinnings remain largely unexplored. Twenty-five healthy participants were involved in this study. Participants were first asked to recall important AMs and assess the emotional ratings of each AM. Four weeks later, they were asked to retrieve the details of both positive and negative AMs during functional magnetic resonance imaging (fMRI) scanning. Behavioral results showed that the emotional valence of negative memories changed more strongly than positive memories over time (i.e., lower consistency). fMRI data showed that the activation level of the precuneus was positively correlated with self-rating valence consistency in the positive AM condition. Additionally, the precuneus connected to a key region of the self-referential network, the medial prefrontal cortex, in both the positive and negative AM conditions. Finally, the precuneus showed stronger connections with the inferior parietal lobule when comparing the positive with the negative AM conditions. Our results suggest that the precuneus is a key area of emotional consistency in positive AMs; this brain area may be involved in the maintenance of a positive self-image by strengthening positive AMs.
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Time is nothing: emotional consistency of autobiographical memory and its neural basis
Abstract
The emotional aspect of autobiographical memories (AMs) is associated with self-related processing, which plays an important role in mental health. However, the emotional consistency dimension of AMs and its neural underpinnings remain largely unexplored. Twenty-five healthy participants were involved in this study. Participants were first asked to recall important AMs and assess the emotional ratings of each AM. Four weeks later, they were asked to retrieve the details of both positive and negative AMs during functional magnetic resonance imaging (fMRI) scanning. Behavioral results showed that the emotional valence of negative memories changed more strongly than positive memories over time (i.e., lower consistency). fMRI data showed that the activation level of the precuneus was positively correlated with self-rating valence consistency in the positive AM condition. Additionally, the precuneus connected to a key region of the self-referential network, the medial prefrontal cortex, in both the positive and negative AM conditions. Finally, the precuneus showed stronger connections with the inferior parietal lobule when comparing the positive with the negative AM conditions. Our results suggest that the precuneus is a key area of emotional consistency in positive AMs; this brain area may be involved in the maintenance of a positive self-image by strengthening positive AMs.
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Training Otolaryngologists in Palliative Care Delivery: An Underutilized Opportunity
Otolaryngology-Head and Neck Surgery, Ahead of Print.
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Absence of Measles Virus Detection from Stapes of Patients with Otosclerosis
Otolaryngology-Head and Neck Surgery, Ahead of Print.
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Custom Mouthguards: Keeping Your Athlete's Smile Safe
Fall is here and school is back in full swing. Weekends are now centered around our student's sporting events.
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Comprehensive analysis of 225 Castleman’s diseases in the oral maxillofacial and neck region: a rare disease revisited
Abstract
Objectives
The aim of the present study was to comprehensively summarize the epidemiological, clinicopathological characteristics, treatments as well as prognosis of Castleman's disease (CD) identified in the oral maxillofacial and neck region.
Materials and methods
Patients with CD in the oral maxillofacial and neck were retrieved from disease registry at our institution from Jan. 1990 to Dec. 2015. Systematic reviews from both English and Chinese literature were performed to collect the detailed information about the oral maxillofacial and neck CD. The epidemiological, clinicopathological data and treatment outcomes were further statistically analyzed.
Results
Four patients with the oral maxillofacial and neck CD were identified and histologically confirmed as hyaline-vascular type. They underwent surgical excision without recurrence during the follow-up. Systematic literature reviews identified 221 cases from 123 eligible articles which satisfied the inclusion criteria. In 225 patients, most patients were diagnosed as unicentric (207) or hyaline-vascular type (205) of CD and identified in the neck, and treated by surgical resection with good prognosis. In contrast, the minority of patients was multicentric or plasma-cell/mixed type and treated by chemotherapy with inferior outcomes. Kaplan-Meir analyses revealed that both clinical and pathological types were significantly associated with patients' overall survival.
Conclusions
Although rare, most cases of the oral maxillofacial neck CD are found in adults and classified as unicentric and hyaline-vascular type of CD. Complete surgical excision is preferred with favorable prognosis for unicentric disease, whereas chemotherapy is usually exploited for multicentric disease with inferior outcomes.
Clinical relevance
These data provide comprehensive information about the epidemiology, clinicopathological features, treatments, and outcomes of the oral maxillofacial and neck CD.
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Qualitative and quantitative metals liberation assessment for characterization of various waste printed circuit boards for recycling
Abstract
Metals liberation and composition are decisive attributes in characterization of e-waste for metal recycling. Though end-of-life printed circuit board (PCB) is an integral part of e-waste as secondary resource reservoir, yet no standardized procedure exists for metals liberation and dissolution for its characterization. Thus, the paper aims at assessment of metals liberation upon comminution employing scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) followed by comparative assessment of the existing United States Environmental Protection Agency (USEPA) digestion procedures, viz., USEPA 3050B, USEPA 3051A, and USEPA 3052, in effective dissolution of metals from comminuted particles of waste PCBs of computer, laptop, mobile phone, and television. Effect of comminution and digestion conditions was assessed to have significant role in metal liberation and dissolution from PCBs. The SEM-EDS analysis demonstrated partial release of metals from the silica matrix of PCBs. The USEPA digestion methods showed statistically significant (P < 0.05) difference with greater dissolution of metals complexed to PCB matrix by the USEPA 3052 method owing to use of strong acid like hydrofluoric acid. Base metals like Cu and Zn and toxic metals such as Pb and Cd were present in abundance in PCBs and in general exceeded the total threshold limit concentration (TTLC). The maximum contents of Cu (20.13 ± 0.04 wt.%) and Zn (1.89 ± 0.05 wt.%) in laptop PCBs, Pb (2.26 ± 0.08 wt.%) in TV PCBs, and Cd (0.0812 ± 0.0008 wt.%) in computer PCBs were observed.
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Quantification of health risks in Ecuadorian population due to dietary ingestion of arsenic in rice
Abstract
In Ecuador alone, 500,000 people in rural areas are estimated to have been exposed to high concentrations of As from water and food, but no quantitative evaluation of health risk has yet been made. The present study quantifies exposure and health risk for the Ecuadorian population from the ingestion of arsenic in white rice. Estimated exposure is correlated with published data on tap water quality and biomarkers of exposure for the population of two towns in the metropolitan area of Quito. Estimated daily intake (EDI) of arsenic for infants living in urban areas of Ecuador is around four times that of European infants, being equal for those livings in rural areas. EDI for the population as a whole is almost twice that of Europe, but between a half and a third of that of Brazil, Bangladesh, and India. Estimated excess lifetime risk (ELTR) for adults is 3 per 10,000, while for infants varies between 10 per 10,000 in rural areas and 20 per 10,000 in urban areas. Future research on arsenic impacts on human health in Ecuador should consider in particular poor populations living in regions where environmental arsenic concentrations are highest, including cross-sectional and longitudinal epidemiologic studies.
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Assessment of facial harmony among Caucasian Spaniards 18 to 60 years of age and its relationship with the golden ratio
Abstract
Background
Throughout history, the perception and definition of beauty and attractiveness have changed and have been influenced by cultural norms. This article analyzes the concept of "facial normality" (faces that are considered normal by 90% of respondents and, therefore, do not require esthetic surgery) among Spaniards of Caucasian ancestry. We also sought to determine the relationship between faces that are considered "normal" and the golden ratio.
Methods
We surveyed 54 respondents (equal numbers of women and men) between the ages of 18 and 60. The surveys followed the visual analog scale (VAS) protocol, and 13,514 responses were obtained. The respondents were asked to evaluate up to nine photographed faces according to their degree of attractiveness.
Results
According to the data obtained, "facial normality" or facial beauty can be defined by the following characteristics: (a) the sizes of the three facial segments (equal in proportion), (b) the width of the nose (narrow in women and average in men), and (c) the profile (straight or slightly retracted in women and straight or slightly prominent in men). In addition, five specific facial proportions were directly related to the golden ratio. Thus, the concept of "normal" can be applied to 90% of faces whose proportions fall within distinct ranges that encompass the value of the golden ratio.
Conclusions
We conclude that a standard perception of "facial normality" and facial beauty does exist. We also observed a general correlation between specific facial proportions and the golden ratio.
Level of Evidence: Not ratable.
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Comprehensive analysis of 225 Castleman’s diseases in the oral maxillofacial and neck region: a rare disease revisited
Abstract
Objectives
The aim of the present study was to comprehensively summarize the epidemiological, clinicopathological characteristics, treatments as well as prognosis of Castleman's disease (CD) identified in the oral maxillofacial and neck region.
Materials and methods
Patients with CD in the oral maxillofacial and neck were retrieved from disease registry at our institution from Jan. 1990 to Dec. 2015. Systematic reviews from both English and Chinese literature were performed to collect the detailed information about the oral maxillofacial and neck CD. The epidemiological, clinicopathological data and treatment outcomes were further statistically analyzed.
Results
Four patients with the oral maxillofacial and neck CD were identified and histologically confirmed as hyaline-vascular type. They underwent surgical excision without recurrence during the follow-up. Systematic literature reviews identified 221 cases from 123 eligible articles which satisfied the inclusion criteria. In 225 patients, most patients were diagnosed as unicentric (207) or hyaline-vascular type (205) of CD and identified in the neck, and treated by surgical resection with good prognosis. In contrast, the minority of patients was multicentric or plasma-cell/mixed type and treated by chemotherapy with inferior outcomes. Kaplan-Meir analyses revealed that both clinical and pathological types were significantly associated with patients' overall survival.
Conclusions
Although rare, most cases of the oral maxillofacial neck CD are found in adults and classified as unicentric and hyaline-vascular type of CD. Complete surgical excision is preferred with favorable prognosis for unicentric disease, whereas chemotherapy is usually exploited for multicentric disease with inferior outcomes.
Clinical relevance
These data provide comprehensive information about the epidemiology, clinicopathological features, treatments, and outcomes of the oral maxillofacial and neck CD.
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Vagus nerve
Vagus nerve: A nerve that supplies nerve fibers to the pharynx (throat), larynx (voice box), trachea (windpipe), lungs, heart, esophagus, and intestinal tract, as far as the transverse portion of the colon. The vagus nerve also brings sensory information back to the brain from the ear, tongue, pharynx, and larynx. The vagus nerve is the tenth cranial nerve. It originates in the medulla oblongata, a part of the brain stem, and extends all the way down from the brain stem to the colon. Complete interruption of the vagus nerve causes a characteristic syndrome in which the soft palate droops on the side where damage occurred, and the gag reflex is also lost on that side. The voice is hoarse and nasal, and the vocal cord on the affected side is immobile. The result is difficulty swallowing (dysphagia) and speaking (dysphonia). The vagus nerve has several important branches, including the recurrent laryngeal nerve.
MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You
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Chronic neuropathic pain negatively associated with employment retention of cancer survivors: evidence from a national French survey
Abstract
Purpose
Chronic neuropathic pain (CNP) is more prevalent among cancer survivors than among the general population. This study aims to investigate the role of CNP on job retention among cancer survivors, 5 years after diagnosis.
Methods
In 2015, 2009 individuals diagnosed with cancer in 2010 were interviewed in the French national survey VIe après le CANcer. Logistic regression investigated the relationship between CNP—measured using the seven-item Douleur Neuropathique 4 (DN4) questionnaire—and employment.
Results
Nine hundred sixty-nine individuals were aged 18–54 and employed at diagnosis and therefore were included. Eighty-two percent were still employed in 2015, 26% had fewer working hours than before diagnosis, and 55% had the same working hours. Thirty percent reported CNP 5 years after diagnosis. These cancer survivors were less likely to be employed in 2015 than those without CNP and, if employed, were more likely to work fewer hours. After adjustment for gender, medical variables (adverse cancer event, prognosis, chemotherapy, and comorbidities) were found to still significantly affect employment retention in cancer survivors, as well as reporting CNP.
Conclusion
Improving CNP screening and management is necessary to reduce its impact on cancer survivors' professional lives.
Implications for cancer survivors
Healthcare policy and medical cancer survivor's follow-up must take into account the importance of the substantial impact of CNP on cancer survivors' daily lives. Therefore, in order to ensure greater employment retention for cancer survivors, raising awareness of care providers about diagnosis and management of CNP is needed.
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IJMS, Vol. 18, Pages 2094: Chronic Δ9-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain
IJMS, Vol. 18, Pages 2094: Chronic Δ9-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain
International Journal of Molecular Sciences doi: 10.3390/ijms18102094
Authors: Pamela Prini Federica Penna Emanuele Sciuccati Tiziana Alberio Tiziana Rubino
Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ9-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ9-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ9-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ9-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ9-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ9-THC adverse effects.
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Fate of toxic metals during estuarine mixing of fresh water with saline water
Abstract
Metals are among the most common environmental pollutants, and their presence in high concentration in waters and biota have devastating effects on flora, fauna, and human health. Flocculation process of metals during estuarine mixing can reduce the environmental hazards of metals and also can provide micronutrients to the aquatic system. The present investigation provides a thorough study of eliminating colloidal elements of copper, manganese, nickel, lead, and zinc during estuarine mixing of Shalmanrood River water with Caspian Sea water in Iran. The processes of flocculation were carried out in six different salinity regimes (0.45–2.4 ppt). The obtained result is indicative of non-conservative behavior of the studied metals. Higher flocculation resulted in a lower salinity regime. The obtained results indicated that most of the metals were eliminated during the initial mixing of fresh water with sea water at 0.45–0.9 ppt salinity interval. The trend of flocculation rates of elements is as follows: Zn (59.3%) > Pb (47.6%) > Mn (37.5%) > Cu (29.2%) > Ni (27%).The annual average load of copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) from Shalmanrood River to Caspian Sea decreases as a result of flocculation process from 9.9, 7.7, 8.9, 5.1, and 23.2 tons per year to 7, 4.8, 6.5, 2.7, and 9.4 tons per year, respectively. According to the cluster analysis, parameters such as temperature, pH, and Eh do not have any impact on flocculation of elements expect for Pb. The only parameter that influences the flocculation of Mn is the salinity. Metal speciation studies that are carried out by Eh-pH software show that the studied metals are present as oxides (Zn, Cu, and Ni) and hydroxides (Mn and Pb).
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Structural Insights into SHARPIN-Mediated Activation of HOIP for the Linear Ubiquitin Chain Assembly
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Jianping Liu, Yingli Wang, Yukang Gong, Tao Fu, Shichen Hu, Zixuan Zhou, Lifeng Pan
The linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ligase complex that catalyzes the formation of linear ubiquitin chain, and it is composed of HOIP, HOIL-1L, and SHARPIN. The E3 activity of HOIP can be effectively activated by HOIL-1L or SHARPIN, deficiency of which leads to severe immune system disorders. However, the underlying mechanism governing the HOIP-SHARPIN interaction and the SHARPIN-mediated activation of HOIP remains elusive. Here, we biochemically and structurally demonstrate that the UBL domain of SHARPIN specifically binds to the UBA domain of HOIP and thereby associates with and activates HOIP. We further uncover that SHARPIN and HOIL-1L can separately or synergistically bind to distinct sites of HOIP UBA with induced allosteric effects and thereby facilitate the E2 loading of HOIP for its activation. Thus, our findings provide mechanistic insights into the assembly and activation of LUBAC.
Graphical abstract
Teaser
LUBAC mediates the formation of linear ubiquitin chains and plays critical roles in numerous signaling pathways. Liu et al. determine the crystal structure of HOIP in complex with SHARPIN and examine the molecular mechanism governing the interaction between two LUBAC components.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjKKa
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A Wnt/Calcium Signaling Cascade Regulates Neuronal Excitability and Trafficking of NMDARs
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Andrea McQuate, Elena Latorre-Esteves, Andres Barria
Wnt signaling controls multiple biological process, particularly the embryonic development of metazoans. Sustained expression of Wnt signaling components in the mature mammalian CNS and their apparent deregulation in certain neuropathologies suggest that it also plays a part beyond embryonic development to regulate normal brain function. We describe a noncanonical Wnt/Ca2+ signaling cascade that regulates the electrophysiological intrinsic properties of rat neurons, resulting in sustained membrane depolarization and the mobilization of Ca2+ from internal stores. These effects require tyrosine kinase-like orphan receptor 2 (RoR2), activation of PLC, and voltage-gated Ca2+ channels. Activation of this signaling cascade then promotes surface expression of N-methyl-D-aspartate receptors (NMDARs) through a SNARE-dependent mechanism. This neuronal Wnt/Ca2+ signaling pathway represents a mechanism for Wnt ligands to regulate normal brain processes in the mature animal and provides a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders where NMDARs are compromised.
Graphical abstract
Teaser
Wnt signaling is a highly conserved signaling mechanism that controls multiple biological processes. McQuate et al. identify a noncanonical Wnt signaling cascade that regulates electrophysiological intrinsic properties of neurons, resulting in sustained membrane depolarization, mobilization of Ca2+ from internal stores, and increased surface expression of NMDAR-type glutamate receptors.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjElM
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An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAA Receptors
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Elizabeth C. Davenport, Valentina Pendolino, Georgina Kontou, Thomas P. McGee, David F. Sheehan, Guillermo López-Doménech, Mark Farrant, Josef T. Kittler
Inhibitory synaptic transmission requires the targeting and stabilization of GABAA receptors (GABAARs) at synapses. The mechanisms responsible remain poorly understood, and roles for transmembrane accessory proteins have not been established. Using molecular, imaging, and electrophysiological approaches, we identify the tetraspanin LHFPL4 as a critical regulator of postsynaptic GABAAR clustering in hippocampal pyramidal neurons. LHFPL4 interacts tightly with GABAAR subunits and is selectively enriched at inhibitory synapses. In LHFPL4 knockout mice, there is a dramatic cell-type-specific reduction in GABAAR and gephyrin clusters and an accumulation of large intracellular gephyrin aggregates in vivo. While GABAARs are still trafficked to the neuronal surface in pyramidal neurons, they are no longer localized at synapses, resulting in a profound loss of fast inhibitory postsynaptic currents. Hippocampal interneuron currents remain unaffected. Our results establish LHFPL4 as a synapse-specific tetraspanin essential for inhibitory synapse function and provide fresh insights into the molecular make-up of inhibitory synapses.
Graphical abstract
Teaser
Davenport et al. identify LHFPL4 as a transmembrane protein that interacts with GABAARs and is essential for their synaptic clustering. Deletion of LHFPL4 results in dramatic cell-type-specific deficits in inhibitory synaptic transmission.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjCKG
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GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Sylvia Pfennig, Franziska Foss, Diane Bissen, Eva Harde, Julia C. Treeck, Marta Segarra, Amparo Acker-Palmer
Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1) binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9) is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP). Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity.
Graphical abstract
Teaser
Activity-dependent AMPA receptor dynamic changes modulate synaptic plasticity. Pfennig et al. show that insertion of new AMPA receptors at the synapse is mediated by the formation of a macromolecular complex at the membrane that includes ApoER2, ephrinB2, and AMPA receptors bridged by the multi-PDZ adaptor protein GRIP1.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjCdE
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Post-transcriptional Inhibition of Hsc70-4/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Alyssa N. Coyne, Ileana Lorenzini, Ching-Chieh Chou, Meaghan Torvund, Robert S. Rogers, Alexander Starr, Benjamin L. Zaepfel, Jennifer Levy, Jeffrey Johannesmeyer, Jacob C. Schwartz, Hiroshi Nishimune, Konrad Zinsmaier, Wilfried Rossoll, Rita Sattler, Daniela C. Zarnescu
Amyotrophic lateral sclerosis (ALS) is a synaptopathy accompanied by the presence of cytoplasmic aggregates containing TDP-43, an RNA-binding protein linked to ∼97% of ALS cases. Using a Drosophila model of ALS, we show that TDP-43 overexpression (OE) in motor neurons results in decreased expression of the Hsc70-4 chaperone at the neuromuscular junction (NMJ). Mechanistically, mutant TDP-43 sequesters hsc70-4 mRNA and impairs its translation. Expression of the Hsc70-4 ortholog, HSPA8, is also reduced in primary motor neurons and NMJs of mice expressing mutant TDP-43. Electrophysiology, imaging, and genetic interaction experiments reveal TDP-43-dependent defects in synaptic vesicle endocytosis. These deficits can be partially restored by OE of Hsc70-4, cysteine-string protein (Csp), or dynamin. This suggests that TDP-43 toxicity results in part from impaired activity of the synaptic CSP/Hsc70 chaperone complex impacting dynamin function. Finally, Hsc70-4/HSPA8 expression is also post-transcriptionally reduced in fly and human induced pluripotent stem cell (iPSC) C9orf72 models, suggesting a common disease pathomechanism.
Graphical abstract
Teaser
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by synaptic failure. Coyne et al. show that in multiple models of ALS, ranging from Drosophila to mice to patient-derived motor neurons, deficits in synaptic vesicle cycling can be explained by dysregulation of the Hsc70-4/HSPA8 chaperone.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjwmi
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M. tuberculosis-Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Murugesan V.S. Rajaram, Eusondia Arnett, Abul K. Azad, Evelyn Guirado, Bin Ni, Abigail D. Gerberick, Li-Zhen He, Tibor Keler, Lawrence J. Thomas, William P. Lafuse, Larry S. Schlesinger
Despite its prominent role as a C-type lectin (CTL) pattern recognition receptor, mannose receptor (MR, CD206)-specific signaling molecules and pathways are unknown. The MR is highly expressed on human macrophages, regulating endocytosis, phagocytosis, and immune responses and mediating Mycobacterium tuberculosis (M.tb) phagocytosis by human macrophages, thereby limiting phagosome-lysosome (P-L) fusion. We identified human MR-associated proteins using phosphorylated and non-phosphorylated MR cytoplasmic tail peptides. We found that MR binds FcRγ-chain, which is required for MR plasma membrane localization and M.tb cell association. Additionally, we discovered that MR-mediated M.tb association triggers immediate MR tyrosine residue phosphorylation and Grb2 recruitment, activating the Rac/Pak/Cdc-42 signaling cascade important for M.tb uptake. MR activation subsequently recruits SHP-1 to the M.tb-containing phagosome, where its activity limits PI(3)P generation at the phagosome and M.tb P-L fusion and promotes M.tb growth. In sum, we identify human MR signaling pathways that temporally regulate phagocytosis and P-L fusion during M.tb infection.
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The human mannose receptor (MR) mediates macrophage phagocytosis and immune regulation. MR-specific signaling remains a major gap in the field. Rajaram et al. identify the importance of FcRγ-chain and Grb2 during MR-mediated phagocytosis and subsequent MR-dependent recruitment of SHP-1 to the M.tb phagosome, thereby limiting PI(3)P generation and phagosome-lysosome fusion.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hLjuLc
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Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Robert Lodge, Jérémy A. Ferreira Barbosa, Félix Lombard-Vadnais, Julian C. Gilmore, Alexandre Deshiere, Annie Gosselin, Tomas Raul Wiche Salinas, Mariana G. Bego, Christopher Power, Jean-Pierre Routy, Petronela Ancuta, Michel J. Tremblay, Éric A. Cohen
Macrophages are heterogeneous immune cells with distinct origins, phenotypes, functions, and tissue localization. Their susceptibility to HIV-1 is subject to variations from permissiveness to resistance, owing in part to regulatory microRNAs. Here, we used RNA sequencing (RNA-seq) to examine the expression of >400 microRNAs in productively infected and bystander cells of HIV-1-exposed macrophage cultures. Two microRNAs upregulated in bystander macrophages, miR-221 and miR-222, were identified as negative regulators of CD4 expression and CD4-mediated HIV-1 entry. Both microRNAs were enhanced by tumor necrosis factor alpha (TNF-α), an inhibitor of CD4 expression. MiR-221/miR-222 inhibitors recovered HIV-1 entry in TNF-α-treated macrophages by enhancing CD4 expression and increased HIV-1 replication and spread in macrophages by countering TNF-α-enhanced miR-221/miR-222 expression in bystander cells. In line with these findings, HIV-1-resistant intestinal myeloid cells express higher levels of miR-221 than peripheral blood monocytes. Thus, miR-221/miR-222 act as effectors of the antiviral host response activated during macrophage infection that restrict HIV-1 entry.
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Using RNA-seq, Lodge et al. compared microRNA profiles of virus producing and bystander macrophages in HIV-1-infected cultures. Among those enhanced in bystanders were microRNAs-221 and -222. These microRNAs are part of an anti-HIV response in bystanders, potentiated by TNF-α activation, which inhibits HIV-1 entry by reducing CD4 expression.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hMw5xO
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Prostaglandin E2 Leads to the Acquisition of DNMT3A-Dependent Tolerogenic Functions in Human Myeloid-Derived Suppressor Cells
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Javier Rodríguez-Ubreva, Francesc Català-Moll, Nataša Obermajer, Damiana Álvarez-Errico, Ricardo N. Ramirez, Carlos Company, Roser Vento-Tormo, Gema Moreno-Bueno, Robert P. Edwards, Ali Mortazavi, Pawel Kalinski, Esteban Ballestar
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels. DNMT3A downregulation erases MDSC-specific hypermethylation, and it abolishes their immunosuppressive capacity. Primary MDSCs isolated from ovarian cancer patients display a similar hypermethylation signature in connection with PGE2-dependent DNMT3A overexpression. Our study links PGE2- and DNMT3A-dependent hypermethylation with immunosuppressive MDSC functions, providing a promising target for therapeutic intervention.
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Rodríguez-Ubreva et al. find that inflammatory factors, such as prostaglandin E2, that are able to redirect the differentiation of precursor myeloid cells toward tolerogenic myeloid-derived suppressor cells (MDSCs) also impose a DNMT3A-dependent fingerprint in myeloid genes that leads to the acquisition of suppressive properties.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hMvAUs
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CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Zicheng Hu, Yu Li, Annemarie Van Nieuwenhuijze, Hilary J. Selden, Angela M. Jarrett, Anna G. Sorace, Thomas E. Yankeelov, Adrian Liston, Lauren I.R. Ehrlich
Upon recognition of auto-antigens, thymocytes are negatively selected or diverted to a regulatory T cell (Treg) fate. CCR7 is required for negative selection of auto-reactive thymocytes in the thymic medulla. Here, we describe an unanticipated contribution of CCR7 to intrathymic Treg generation. Ccr7−/− mice have increased Treg cellularity because of a hematopoietic but non-T cell autonomous CCR7 function. CCR7 expression by thymic dendritic cells (DCs) promotes survival of mature Sirpα− DCs. Thus, CCR7 deficiency results in apoptosis of Sirpα− DCs, which is counterbalanced by expansion of immature Sirpα+ DCs that efficiently induce Treg generation. CCR7 deficiency results in enhanced intrathymic generation of Tregs at the neonatal stage and in lymphopenic adults, when Treg differentiation is critical for establishing self-tolerance. Together, these results reveal a complex function for CCR7 in thymic tolerance induction, where CCR7 not only promotes negative selection but also governs intrathymic Treg generation via non-thymocyte intrinsic mechanisms.
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CCR7 promotes thymocyte medullary entry and is thus required for negative selection. Hu et al. show that CCR7 also regulates intrathymic generation of regulatory T cells (Tregs) through a non-T cell intrinsic mechanism. CCR7 regulates the composition of the thymic conventional DC compartment, which, in turn, restrains intrathymic Treg generation.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hMvzjm
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Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity
Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Byung-Seok Kim, Huiping Lu, Kenji Ichiyama, Xiang Chen, Yi-Bing Zhang, Nipun A. Mistry, Kentaro Tanaka, Young-hee Lee, Roza Nurieva, Li Zhang, Xuexian Yang, Yeonseok Chung, Wei Jin, Seon Hee Chang, Chen Dong
Th17 cells are potent mediators in autoimmune diseases, and RORγt is required for their development. Recent studies have shown that RORγt+ Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORγt+ Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORγt+ Treg cells in their transcriptomes, peripheral RORγt+ Treg cells were derived from Foxp3+ thymic Treg cells in an antigen-specific manner. Development of these RORγt+ Treg cells, coined T regulatory 17 (Tr17) cells, depended on IL-6/Stat3 signaling. Tr17 cells showed suppressive activity against antigen-specific effector T cells in vitro. In addition, Tr17 cells efficiently inhibited myelin-specific Th17-cell-mediated CNS auto-inflammation in a passive EAE model. Collectively, our study demonstrates that Tr17 cells are effector Treg cells that potentially restrict autoimmunity.
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Kim et al. find that RORγt+Foxp3+ T regulatory 17 (Tr17) cells are induced in lymph nodes after immunization. Tr17 cells are generated from thymic Treg cells in an antigen-specific manner through Stat3 signaling. Their data suggest that Tr17 cells represent antigen-specific effector Treg cells that can regulate Th17-cell-dependent autoimmunity.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hMvZWY
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What you need to know about airway management
Sponsored by BoundTree and Ambu By Jonathan Lee for EMS1 BrandFocus Airway management in the prehospital environment is messy business. A recent study of prehospital intubation in trauma found that 44.3 percent of the patients had gross contamination of the airway at the time of intubation (most commonly blood, followed by vomit, teeth or brain). While the literature is divided on whether prehospital ...
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Interleukin-34 Promotes Fibrocyte Proliferation
Journal of Interferon & Cytokine Research , Vol. 0, No. 0.
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Chemokine CXC Ligand 13 (CXCL13) in Cerebrospinal Fluid Can Be Used as an Early Diagnostic Biomarker for Lyme Neuroborreliosis: A Meta-Analysis
Journal of Interferon & Cytokine Research , Vol. 0, No. 0.
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AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca2+/calmodulin (CaM) dependence of Ca2+/CaM-dependent protein kinase kinase {beta} [Enzymology]
The Ca2+/calmodulin-dependent protein kinase kinase β(CaMKKβ)/5′AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca2+-dependent metabolic pathways and cancer growth. Unlike recombinant CaMKKβ that exhibits higher basal activity (autonomous activity), activation of the CaMKKβ/AMPK signaling pathway requires increased intracellular Ca2+ concentrations. Moreover, the Ca2+/CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases. However, the effects of proximal downstream kinases on CaMKKβ activity have not yet been evaluated. Here, we demonstrate feedback phosphorylation of CaMKKβ at multiple residues by CaMKKβ-activated AMPK in addition to autophosphorylation in vitro, leading to reduced autonomous, but not Ca2+/CaM-activated, CaMKKβ activity. MS analysis and site-directed mutagenesis of AMPK phosphorylation sites in CaMKKβ indicated that Thr144 phosphorylation by activated AMPK converts CaMKKβ into a Ca2+/CaM-dependent enzyme, as shown by completely Ca2+/CaM-dependent CaMKK activity of a phosphomimetic Thr144Glu CaMKKβ mutant. CaMKKβ mutant analysis indicated that the C-terminal domain (residues 471−587) including the autoinhibitory region plays an important role in stabilizing an inactive conformation in a Thr144 phosphorylation-dependent manner. Furthermore, immunoblot analysis with antiphospho-Thr144 antibody revealed phosphorylation of Thr144 in CaMKKβ in transfected COS-7 cells that was further enhanced by exogenous expression of AMPKα. These results indicate that AMPK-mediated feedback phosphorylation of CaMKKβ regulates the CaMKKβ/AMPK signaling cascade and may be physiologically important for intracellular maintenance of Ca2+-dependent AMPK activation by CaMKKβ.
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Sumoylation regulates nuclear accumulation and signaling activity of the soluble intracellular domain of the erbb4 receptor tyrosine kinase [Molecular Bases of Disease]
Erb-B2 receptor tyrosine kinase 4 (ErbB4) is a kinase that can signal via a proteolytically released intracellular domain (ICD) in addition to classical receptor tyrosine kinase-activated signaling cascades. Previously, we have demonstrated that ErbB4 ICD is posttranslationally modified by the small ubiquitin-like modifier (SUMO) and functionally interacts with the PIAS3 SUMO E3 ligase. However, direct evidence of SUMO modification in ErbB4 signaling has remained elusive. Here, we report that the conserved lysine residue 714 in the ErbB4 ICD undergoes SUMO modification, which was reversed by sentrin-specific proteases (SENPs) 1, 2 and 5. Although ErbB4 kinase activity was not necessary for the SUMOylation, the SUMOylated ErbB4 ICD was tyrosine phosphorylated to a higher extent than unmodified ErbB4 ICD. Mutation of the SUMOylation site neither compromised ErbB4-induced phosphorylation of the canonical signaling pathway effectors Erk1/2, Akt, or STAT5 nor ErbB4 stability. In contrast, SUMOylation was required for nuclear accumulation of the ErbB4 ICD. We also found that Lys-714 was located within a leucine-rich stretch, which resembles a nuclear export signal, and could be inactivated by site-directed mutagenesis. Furthermore, SUMOylation modulated the interaction of ErbB4 with chromosomal region maintenance 1 (CRM1), the major nuclear export receptor for proteins. Finally, the SUMO acceptor lysine was functionally required for ErbB4 ICD-mediated inhibition of mammary epithelial cell differentiation in a three-dimensional cell culture model. Our findings indicate that a SUMOylation-mediated mechanism regulates nuclear localization and function of the ICD of ErbB4 receptor tyrosine kinase.
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Proteolytic degradation of Regulator of G Protein Signaling 2 facilitates temporal regulation of Gq/11 signaling and vascular contraction [Cell Biology]
Regulator of G protein signaling 2 (RGS2) controls signaling by receptors coupled to the Gq/11 class heterotrimeric G proteins. RGS2 deficiency causes several phenotypes in mice and occurs in several diseases, including hypertension where a proteolytically unstable RGS2 mutant has been reported. However, the mechanisms and functions of RGS2 proteolysis remain poorly understood. Here we addressed these questions by identifying degradation signals in RGS2, and studying dynamic regulation of Gq/11-evoked Ca2+ signaling and vascular contraction. We identified a novel bipartite degradation signal in the N-terminal domain of RGS2. Mutations disrupting this signal blunted proteolytic degradation downstream of E3 ubiquitin ligase binding to RGS2. Analysis of RGS2 mutants proteolyzed at various rates and the effects of proteasome inhibition indicated that proteolytic degradation controls agonist efficacy by setting RGS2 protein expression levels, and affecting the rate that cells regain agonist responsiveness as synthesis of RGS2 stops. Analyzing contraction of mesenteric resistance arteries supported the biological relevance of this mechanism. Because RGS2 mRNA expression often is strikingly and transiently up- and then down-regulated upon cell stimulation, our findings indicate that proteolytic degradation tightly couples RGS2 transcription, protein levels and function. Together these mechanisms provide tight temporal control of Gq/11-coupled receptor signaling in the cardiovascular, immune and nervous systems.
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Insights into the roles of non-catalytic residues in the active site of a GH10 xylanase with activity on cellulose [Enzymology]
Bifunctional glycoside hydrolases have potential for cost saving in enzymatic decomposition of plant cell wall polysaccharides for biofuels and bio-based chemicals. The N-terminal GH10 domain of a bifunctional multimodular enzyme CbXyn10C/Cel48B from Caldicellulosiruptor bescii, is an enzyme able to degrade xylan and cellulose simultaneously. However, the molecular mechanism underlying its substrate promiscuity has not been elucidated. Herein, we discovered that the binding cleft of CbXyn10C would have at least six sugar binding subsites by using isothermal titration calorimetry analysis of the inactive E140Q/E248Q mutant with xylo- and cellooligosaccharides. This was confirmed by determining the catalytic efficiency of the wild-type enzyme on these oligosaccharides. The free form and complex structures of CbXyn10C with xylose- or glucose-configured oligosaccharide ligands were further obtained by crystallographic analysis and molecular modeling and docking. CbXyn10C was found to have a typical (β/α)8-TIM barrel fold and "salad-bowl" shape of GH10 enzymes. In complex structure with xylo-oligosaccharides, seven sugar-binding subsites were found and many residues responsible for substrate interactions were identified. Site-directed mutagenesis indicated that six and ten amino acid residues were key residues for xylan and cellulose hydrolysis, respectively. The most important residues are centered on the subsites -2 and -1 near the cleavage site, while residues playing moderate roles could be located at more distal regions of the binding cleft. Manipulating the residues directly or indirectly interacting with substrates in the distal regions improved the activity of CbXyn10C on xylan and cellulose. Most of the key residues for cellulase activity are conserved across GH10 xylanases. Revisiting randomly selected GH10 enzymes revealed unreported cellulase activity, indicating that the dual function may be a more common phenomenon than has been expected.
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PET-positive bone lesion due to Langerhans cell histiocytosis after BEACOPP therapy for Hodgkin lymphoma: how anamnesis, histopathological accuracy, and molecular analysis could resolve a clinical dilemma
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Clinicopathological features of primary splenic follicular lymphoma
Abstract
Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy. Extranodal invasion by FL generally involves the bone marrow, skin, and duodenum; splenic infiltration often occurs in the advanced stages. However, primary splenic FL is very rare. Hence, few studies have been performed on splenic FL, and its clinicopathological features have not been established. This study aimed to investigate the clinicopathological features of primary splenic FL, as compared to nodal FL. We analyzed 17 patients diagnosed with primary splenic FL and 153 control patients with systemic FL. Hepatitis C virus (HCV)-positive status was significantly more common in patients with splenic FL than in the control patients (p = 0.02). Ann Arbor stage III or IV (p = 0.0003) and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) (p = 0.03) were significantly less common in patients with splenic FL than in the control patients; however, the overall and progression-free survival curves were not significantly different between the groups. Among the 17 patients with splenic FL, the progression-free survival was significantly worse in patients who underwent splenectomy without receiving postoperative chemotherapy than in those who did (p = 0.03). These results suggest that primary splenic FL should be considered different from systemic FL; accordingly, its management should also be conducted differently.
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A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry
Abstract
Prediction of response to erythropoietin stimulating agents (ESAs) in anemic MDS patients is often based on the Nordic score. We wished to validate the Nordic score (IWG 2006 response criteria) in a larger cohort and determine if other variables such as IPSS/IPSS-R, ferritin, LDH, and a novel European ESA response score (Santini 2013) were of prognostic importance. We analyzed 208 ESA-treated MDS patients (WHO 2008 criteria) from a prospective registry. Ninety-four and 93% had lower risk scores by IPSS (low/int − 1) and IPSS-R (low/very low), respectively. Erythroid response was achieved in 94 patients (47%); responses were similar with erythropoietin (50%) and darbepoetin (39%; p = 0.2). The Nordic and European scores were both validated on univariate analysis. Variables independently predictive of response in multivariate analysis were low-risk IPSS score (OR 0.1, p = 0.0016) and serum EPO level < 100 mIU/mL (OR 8.7, p < 0.0001). We propose a new ESA response score, consisting of (a) IPSS low score (1 point) and (b) serum EPO levels < 100 mIU/ml (2 points), yielding scores ranging from 0 to 3, with response rates varying from 17 to 81%. The Nordic score has validity but we observed lower than the expected response rates in the best risk group. Our proposed scoring system appears more discriminating but needs validation.
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Microwave-assisted extraction of Nigella sativa L. essential oil and evaluation of its antioxidant activity
Abstract
It has been previously reported that the essential oil of Nigella sativa L. seeds and its major active component, thymoquinone (TQ), possess a broad variety of biological activities and therapeutic properties. In this work, microwave-assisted extraction (MAE) of the essential oil from Nigella sativa L. seeds and its antioxidant activity were studied. Response surface methodology based on central composite design was used to evaluate the effects of extraction time, irradiation power and moisture content on extraction yield and TQ content. Optimal parameters obtained by CCD and RSM were extraction time 30 min, irradiation power 450 W, and moisture content 50%. The extraction yield and TQ content of the essential oil were 0.33 and 20% under the optimum conditions, respectively. In contrast, extraction yield and TQ amount of oil obtained by hydrodistillation (HD) were 0.23 and 3.71%, respectively. The main constituents of the essential oil extracted by MAE and HD were p-cymene, TQ, α-thujene and longifolene, comprising more than 60% of total peak area. The antioxidant capacity of essential oils extracted by different methods were evaluated using 2,2-diphenyl-1-picrylhydrazyl and Ferric reducing antioxidant power assays, and compared with traditional antioxidants. The results showed that MAE method was a viable alternative to HD for the essential oil extraction from N. sativa seeds due to the excellent extraction efficiency, higher thymoquinone content, and stronger antioxidant activity.
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Construction of a lateral flow strip for detection of soymilk in milk
Abstract
A lateral flow based detection method for ascertaining the presence of soymilk in whole bovine milk has been described. The method uses commercially available rabbit anti-soy protein antibodies conjugated to gold nanoparticles (AuNPs) wherein soymilk protein in adulterated milk and soymilk protein at test line competes for limited antibodies. At control line, anti-rabbit immunoglobulin was immobilized for ensuring flow properties of antibody—conjugated AuNPs. Absence or diminished intensity of band at test line indicates presence of soymilk in milk. The soymilk detection limit was 1.75% (v/v) in whole bovine milk and results are available in 5 min. Constructed lateral flow device can be used for on-spot examination of soymilk in milk.
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Functional properties of Mozzarella cheese for its end use application
Abstract
Cheese is an extremely versatile food product that has a wide range of flavor, textures and end uses. The vast majority of cheese is eaten not by itself, but as part of another food. As an ingredient in foods, cheese is required to exhibit functional characteristics in the raw as well as cooked forms. Melting, stretching, free-oil formation, elasticity and browning are the functional properties considered to be significant for Mozzarella cheese. When a cheese is destined for its end use, some of its unique characteristics play a significant role in the products acceptability. For instance pH of cheese determines the cheese structure which in turn decides the cheese shredability and meltability properties. The residual galactose content in cheese mass determines the propensity of cheese to brown during baking. Development of 'tailor-made cheese' involves focusing on manipulation of such unique traits of cheese in order to obtain the desired characteristics for its end use application suiting the varied consumer's whims and wishes. This comprehensive review paper will provide an insight to the cheese maker regarding the factors determining the functional properties of cheese and also for the pizza manufacturers to decide which age of cheese to be used which will perform well in baking applications.
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Antioxidant activity, sterol and fatty acid compositions of Turkish olive oils as an indicator of variety and ripening degree
Abstract
This study was carried out to determine the effect of three ripening stages (green, spotted and ripe) on fatty acid, sterol composition and antioxidant activity of olive oils from three olive varieties (Sarı Hasebi, Gemlik and Halhalı) widely grown in the eastern Mediterranean region of Turkey. The variety had a significant effect on the fatty acids, sterols and total phenolic content. Halhalı oil had the lowest oleic acid content (67.28%), while Sarı Hasebi oil had the highest (75.61%). Total phenolic content varied between 163.02 mg GAE/kg oil and 749.28 mg GAE/kg oil. Halhalı oil showed the highest antioxidant activity (IC50 = 66 µg/ml) whereas Sarı Hasebi oil showed the lowest one (IC50 = 2617 µg/ml). The total content of sterols in olive oils ranged from 358 mg/kg in Sarı Hasebi to 1092.33 mg/kg in Halhalı. The β-sitosterol content of olive oils varied between 80.72 (Sarı Hasebi) and 87.81% (Halhalı). ∆-5-avenasterol content ranged between 3.34 (Halhalı) and 7.30% (Gemlik). Variety and ripening degree significantly affected the β-sitosterol, ∆-5-avenasterol and erythrodiol + uvaol contents of oils. Finally, these results showed that sterol and fatty acid compositions can be used as indicators of variety and ripening degree among virgin olive oils.
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Mendelism: New Insights from Gregor Mendels Lectures in Brno
Hui Zhang<br />Sep 1, 2017; 207:1-8<br />PERSPECTIVES
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Exact Calculation of the Joint Allele Frequency Spectrum for Isolation with Migration Models
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Contrasting Determinants of Mutation Rates in Germline and Soma
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Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research
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Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions
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Benchmarking Relatedness Inference Methods with Genome-Wide Data from Thousands of Relatives
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Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level
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The Recombination Landscape in Wild House Mice Inferred Using Population Genomic Data
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MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila melanogaster
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DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression
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A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans
Patrick D. Brophy<br />Sep 1, 2017; 207:215-228<br />Developmental and behavioral genetics
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Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1
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Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase
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Balancing Selection in Species with Separate Sexes: Insights from Fisher's Geometric Model
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Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin
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Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug-Placebo Experiment and Bayesian Causal Analysis
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Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin in Drosophila melanogaster
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Genetic Evidence That Synaptonemal Complex Axial Elements Govern Recombination Pathway Choice in Mice
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Transcriptional Networks for Alcohol Sensitivity in Drosophila melanogaster
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Thirty-One Flavors of Drosophila Rab Proteins
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The Beginning of the Age of Giants
Southern Africa preserves the early days of massive dinosaurs.
-- Read more on ScientificAmerican.com
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Immediate completion lymph node dissection in stage IIIA melanoma does not provide significant additional staging information beyond EORTC SN tumour burden criteria
Source:European Journal of Cancer
Author(s): Max F. Madu, Viola Franke, Maarten M. Bruin, Danique M.S. Berger, Carolien Bierman, Katarzyna Jóźwiak, Willem M.C. Klop, Michel W.J.M. Wouters, Alexander C.J. van Akkooi, Bart A. Van de Wiel
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Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: Validation study and biological rationale
Source:European Journal of Cancer, Volume 86
Author(s): Andrea Casadei Gardini, Luca Faloppi, Serena De Matteis, Francesco Giuseppe Foschi, Nicola Silvestris, Francesco Tovoli, Vincenzo Palmieri, Giorgia Marisi, Oronzo Brunetti, Umberto Vespasiani-Gentilucci, Giuseppe Perrone, Martina Valgiusti, Anna Maria Granato, Giorgio Ercolani, Giulia Negrini, Emiliano Tamburini, Giuseppe Aprile, Alessandro Passardi, Daniele Santini, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
PurposeIn 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance.Patients and methodsWe analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples.ResultsIn HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin (P < .0001). We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) (P = .013).ConclusionsOur findings could be attributed to increased tumour aggressiveness and resistance to sorafenib caused by chronic treatment with metformin.
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‘Corrigendum to “Severe hepatitis under combined immunotherapy: Resolution under corticosteroids plus anti-thymocyte immunoglobulins” [Eur J Cancer 81 (August 2017) 203–205]’
Source:European Journal of Cancer
Author(s): Iris Spänkuch, Maximilian Gassenmaier, Ioanna Tampouri, Seema Noor, Andrea Forschner, Claus Garbe, Teresa Amaral
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Weaknesses and capacities affecting the Prehospital emergency care for victims of road traffic incidents in the greater Kampala metropolitan area: a cross-sectional study
Pre-hospital emergency care is a vital and integral component of health systems particularly in the resource constrained countries like Uganda. It can help to minimize deaths, injuries, morbidities, disabiliti...
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Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells—Power of nutraceuticals
Publication date: Available online 3 October 2017
Source:Advances in Biological Regulation
Author(s): James A. McCubrey, Steve L. Abrams, Kvin Lertpiriyapong, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Saverio Candido, Massimo Libra, Ramiro M. Murata, Pedro L. Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Linda S. Steelman
Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These "healthy" components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/potentials. Understanding the effects of various natural products on cancer cells may enhance their usage as anti-proliferative agents which may be beneficial for many health problems. In this manuscript, we discuss and demonstrate how certain nutraceuticals may enhance other anti-cancer drugs to suppress proliferation of cancer cells.
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Influence Parameters on Nitriding Process of Ferromanganese Alloy
A 24 factorial design technique was used to investigate the magnitude effect of temperature, time, carbon percent, and pressure of the nitriding process of gas solid reaction of ferromanganese. The design was based on experiments results obtained from nitriding of two grades of ferromanganese alloys containing 0.23% C and 7.1% C at temperatures 700°C and 950°C, during time of 2 hours and 6 hours and with nitrogen pressure of 1 and 8 bar. The required calculations were carried out by Matlab. It was found that the highest positive effect was temperature while the carbon content has the highest negative effect. Nitrogen pressure has more positive effect than time. The interaction combination between two parameters or more of temperature, nitrogen pressure, and time has positive influence with different extent. The interaction combination between carbon and one or more of parameters of time, temperature, or nitrogen pressure has negative effect on nitriding process. The driven models were found to be in good agreement with the experiments and published work of nitriding process of ferromanganese containing different carbon contents (0.23–7.1%) in temperature range 700°C–950°C, with nitrogen pressure up to 8 bar, and during time of 2–6 hours.
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Wind Tunnel Tests on Aerodynamic Characteristics of Ice-Coated 4-Bundled Conductors
Wind tunnel tests were carried out to obtain the static aerodynamic characteristics of crescent iced 4-bundled conductors with different ice thicknesses, initial ice accretion angles, bundle spaces, and wind attack angles. The test models were made of the actual conductors and have a real rough surface. Test results show that the influence of wake interference on the drag coefficients of leeward subconductors is obvious. The interference angle range is larger than 20° and the drag coefficient curves of leeward subconductors have a sudden decrease phenomenon at some certain wind attack angles. The absolute value of the lift and moment coefficient increases with the increase of the ice thickness. In addition, the galloping of the iced subconductor may occur at the angle of wind attack near ±20° and the wake increases the moment coefficient. The variation of initial ice accretion angle has a significant influence on the aerodynamic coefficients. The aerodynamic coefficient curves exhibit a "moving" phenomenon at different initial ice accretion angles. The bundle spaces have a great influence on the moment coefficient of leeward thin ice-coated conductors. With the increase of ice thickness, the bundle spaces generally have little influence on the aerodynamic coefficients.
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OM-101 Decreases the Fibrotic Response Associated with Proliferative Vitreoretinopathy
Purpose. This study aimed to investigate the effect of OM-101 on the fibrotic response occurring in proliferative vitreoretinopathy (PVR) in an animal model. Methods. Antifibrotic effect of OM-101 was investigated in vivo. As control, eight weeks old c57black mice underwent intravitreal injection with Hepes (group A) or dispase (0.3 units), to induce retinal detachment (RD) and PVR. The dispase-injected mice were randomly divided into two groups B and C ( mice); in group C, the eyes were treated with intravitreal injection of OM-101 (3 μl), and group B with PBS, as a control. After additional five days, mice were injected with the same initial treatment. Three days later, mice were euthanized, and the eyes were enucleated and processed for histological analysis. Results. Intravitreal injection of dispase caused RD in 64% of the mice in group B, and 93% of those mice had PVR. Only 32% of mice treated with OM-101 and dispase (group C) developed RD, and only 25% of those developed PVR. Conclusions. OM-101 was found effective in reducing the incidence of RD and PVR maintaining the normal architecture of the retina. This study suggests that OM-101 is a potentially effective and safe drug for the treatment of PVR patients.
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A Cycle Deep Belief Network Model for Multivariate Time Series Classification
Multivariate time series (MTS) data is an important class of temporal data objects and it can be easily obtained. However, the MTS classification is a very difficult process because of the complexity of the data type. In this paper, we proposed a Cycle Deep Belief Network model to classify MTS and compared its performance with DBN and KNN. This model utilizes the presentation learning ability of DBN and the correlation between the time series data. The experimental results showed that this model outperforms other four algorithms: DBN, KNN_ED, KNN_DTW, and RNN.
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Effect of antibiotics for infectious diarrhea on the duration of hospitalization: A retrospective cohort study at a single center in Japan from 2012 to 2015
Publication date: Available online 3 October 2017
Source:Journal of Infection and Chemotherapy
Author(s): Yosuke Sasaki, Yoshitaka Murakami, Hiroaki Zai, Hitoshi Nakajima, Yoshihisa Urita
ObjectiveRoutine empirical antimicrobial therapy for patients with infectious diarrhea is not recommended in general practice. Conversely, prescription of empirical antibiotics for hospitalized patients remains controversial due to a lack of studies providing evidence for its benefits. Thus, this study aimed to examine whether empirical antimicrobial therapy would shorten the hospitalization duration for infectious diarrhea patients.MethodsThis single-center, retrospective cohort study was performed at the Department of General Medicine and Emergency Care, Toho University Medical Center Omori Hospital, using medical records. Adult patients (aged ≥16 years) hospitalized for infectious diarrhea from 2012 to 2015 were enrolled. The primary outcome was the duration of hospitalization. Risk factors examined in parallel to antibiotic therapy included age, sex, relevant medical history, probiotics use, vital signs, leukocyte count, liver and renal functions, and microbiological data.ResultsWe enrolled 138 and 50 patients treated with and without antimicrobial therapy, respectively. The median hospitalization periods were 6.0 days (interquartile range, 4.0–7.0 days) and 5.0 days (interquartile range, 3.25–6.0 days) for patients treated with and without antibiotics, respectively (p = 0.007). Multiple regression showed that empiric antimicrobial therapy (p = 0.017), advanced age (p = 0.003), hematochezia (p = 0.008), elevated serum creatinine (p < 0.001), and elevated serum C-reactive protein (p = 0.002) were significant risk factors of longer hospitalization duration.ConclusionEmpirical antimicrobial therapy was found to relate to a longer hospitalization duration for infectious diarrhea patients. Although its effects on the patients' symptoms were not evaluated, our results suggest that empirical antimicrobial therapy should be administered cautiously to not only outpatients, but also hospitalized patients.
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JAID/JSC Guidelines for Infection Treatment 2015−Intestinal infections
Publication date: Available online 3 October 2017
Source:Journal of Infection and Chemotherapy
Author(s): Kenji Ohnishi, Yusuke Ainoda, Akifumi Imamura, Sentaro Iwabuchi, Masumi Okuda, Takashi Nakano
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Tooth Regeneration Market is Expected to Witness a CAGR of 7.1% During the Period 2017 - 2025
The global tooth regeneration addressable market is expected to be pegged at an astounding 4,633.3 million dental implant procedures by 2024 and is expected to expand at a CAGR of 7.1% during the period 2016 - 2024. However, commercialization of the product is expected to take place post-2024.
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Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry
Abstract
In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.
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Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry
Abstract
In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.
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Aldose reductase inhibitor, fidarestat regulates mitochondrial biogenesis via Nrf2/HO1/AMPK pathway in colon cancer cells
Although we have shown earlier that aldose reductase (AR) inhibitors prevent colorectal cancer cell (CRC) growth in culture as well as in nude mice xenografts, the mechanism(s) is not well understood. In this study, we have investigated how AR inhibition prevents CRC growth by regulating the mitochondrial biogenesis via Nrf2/HO-1pathway. Incubation of CRC cells such as SW-480, HT29, and HCT116 with AR inhibitor, fidarestat that non-covalently binds to the enzyme, increases the expression of Nrf2.
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Is Subcranial Le Fort III Plus Le Fort I Osteotomy Stable?
The purpose of this study was to test whether associated subcranial Le Fort III (sLF III) and Le Fort I (LF I) osteotomies are stable after large advancements of the middle third of the face and maxilla. The authors designed a retrospective study and enrolled a sample of consecutive patients with midface hypoplasia treated with associated sLF III and LF I osteotomies in this IRB-approved study between September 2013 and February 2015. To test whether the long-term stability was satisfactory, the authors compared cephalometric changes from immediately after surgery to 18 months after surgery taken from multi-slice computed tomography using two different third-party imaging software programs.
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Orthognathic surgery “again” to correct aesthetic failure of primary surgery: Report on outcomes and patient satisfaction in 70 consecutive cases
An increasing number of patients complain about unsatisfactory aesthetic outcomes of orthognathic surgery, desiring reoperation to improve facial aesthetics. The aims of this article are to present a wide range of aesthetic reasons to justify a secondary orthognathic surgery and to report aesthetic outcomes and patient satisfaction after reoperation.
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Quantitative assessment of orbital fractures in Asian patients: CT measurement of orbital volume
Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume.
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Conservative treatment of children with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible
Chronic diffuse sclerosing osteomyelitis (DSO) of the mandible is a rare disease of unknown etiology. It has been suggested that overuse of the masticatory muscles, tendoperiostitis (TP), is a contributing factor for DSO. Therefore, we tested this hypothesis by treating consecutive children with conservative therapy.All patients were treated with conservative therapy, comprising occlusal splint therapy, physiotherapy, and/or disease counselling. Pain intensity on a visual analogue scale (VAS) and pain frequency in number of days per 3 months were recorded before the start of treatment, and at 3, 6, and 12 months after treatment initiation.
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Aldose reductase inhibitor, fidarestat regulates mitochondrial biogenesis via Nrf2/HO1/AMPK pathway in colon cancer cells
Although we have shown earlier that aldose reductase (AR) inhibitors prevent colorectal cancer cell (CRC) growth in culture as well as in nude mice xenografts, the mechanism(s) is not well understood. In this study, we have investigated how AR inhibition prevents CRC growth by regulating the mitochondrial biogenesis via Nrf2/HO-1pathway. Incubation of CRC cells such as SW-480, HT29, and HCT116 with AR inhibitor, fidarestat that non-covalently binds to the enzyme, increases the expression of Nrf2.
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Asthma disease as cause of admission to hospitals due to exposure to ambient oxidants in Mashhad, Iran
Abstract
Nowadays, asthma is one of the most common chronic respiratory diseases, worldwide. Many reports have emphasized the correlation between the short-term exposure to the ambient air pollutants and acute respiratory diseases, especially among children with asthmatic symptoms. The aim of this study was to evaluate the relationship between the exposure to three atmospheric antioxidants (NO2, SO2, and O3) and hospital admission due to asthmatic disease (HAAD) in the city of Mashhad, Iran. The concentrations of atmospheric antioxidants were obtained from the real-time monitoring stations located in the city. The collected data were employed for developing predictive models in the AirQ software. In order to investigate the association between short-term exposure to air pollutants and HAAD, the study participants were categorized into two age groups: less than 15 and from 15 to 64 years old. The results indicated that in people less than 15 years increase in NO2 (attributable proportion (AP) = 3.775%, 95% CI 0.897–6.883%), SO2 (AP = 3.649%, 95% CI 1.295–5.937%), and O3 (AP = 0.554%,95% CI 0.00–3.321) results in increase in HAAD. While for those aged between 15 and 64 years, the AP was 4.192% (95% CI 0.450–7.662%) for NO2; 0.0% (95% CI 0.00–1.687%) for SO2; and 0.236% (95% CI 0.00–1.216%) for O3. The number of asthmatic cases who were less than 15 years admitted to the hospitals during the study period was higher than that of those within the age groups between 15 and 64 years as a consequence of exposure to NO2 (101 vs. 75), SO2 (98 vs. 0), and O3 (15 vs. 3), respectively. To the best of our knowledge, the AirQ model has not been applied before to estimate the effect of atmospheric antioxidant exposure on hospital admission because of asthma disease. Eventually, this model is proposed to be applicable for other cities around the world.
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Major and trace metals in suspended and bottom sediments of the Mandovi and Zuari estuaries, western India: distribution, source, and pollution
Abstract
Major elements and trace metals in suspended sediments along transect stations of the Mandovi and Zuari estuaries showed three types of distribution: (a) high concentrations of most metals (Al, Fe, Mn, Cr, Pb, Cu, Ni, Zn, Co, Sc, Mo, and U) in the upper estuary and their decreasing concentrations seaward in every season, (b) lower concentrations of some metals (Mg, Cr, Zr, V, Al, Th) in the upper estuary and bay and their increased concentrations in the lower estuary, and (c) higher concentrations of some metals (Cu, Ni, Zn, Pb, and Cr) in the upper estuary and bay and their decreased concentrations in the lower estuary. Mn was the most significant pollutant in both the estuaries. The Zn, Cr, Fe, and Mo in Mandovi during the monsoon and post-monsoon and, Pb, Ni, and Cr in Zuari during the post- and pre-monsoons were in the range "moderately to heavily polluted." The pollution load index of metals was high at upstream stations, with higher values in Mandovi during monsoon and Zuari during the post- and pre-monsoons. Most trace metals were correlated with Fe and Mn indicating their association primarily with Fe-Mn ore material. The principal component analysis indicated natural and anthropogenic inputs and the latter was predominantly related to ore material in both the estuaries. The distribution factor was high for Al, Mg, Zr, Th, and U in < 2-μm fraction and Cr, Cu, Ni, Zn, Co, V, Sc, and Zr in 2–4-μm size fraction sediments suggesting two sources of sediments. More than 60% concentrations of all trace metals were associated with < 2-μm fraction sediments. The distribution of trace metals along transect was affected by the physico-chemical conditions of the estuary, grain size of sediments, and anthropogenic contribution of metals.
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In response to the commentary of Dr. Lou on treatment of laryngopharyngeal reflux using a sleep positioning device: A prospective cohort study
The authors of the paper "Treatment of Laryngopharyngeal Reflux Using a Sleep Positioning Device: A Prospective Cohort Study [1]," would like to begin by thanking Dr. Lou and our scientific community for interest in this work. We further appreciate the commentary of Dr. Lou and the opportunity to further discuss this work in the American Journal of Otolaryngology. The principle critique of this commentary is that our study may overestimate treatment effect due to misdiagnosis or concurrent diagnosis of GERD.
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