Αρχειοθήκη ιστολογίου

Δευτέρα 3 Ιουλίου 2017

In vitro evaluation of the prebiotic effect of red and white grape polyphenolic extracts

Abstract

Nowadays, the strong relationship between diet and health is well known. Although the primary role of diet is to provide nutrients to fulfill metabolic requirements, the use of foods to improve health and the state of well-being is an idea increasingly accepted by society in the last three decades. During the last years, an important number of scientific advances have been achieved in this field and, although in some situations, it is difficult to establish a distinction between "harmful" and "good" bacteria, experts agree in classifying the genera Bifidobacterium and Lactobacillus as beneficial bacteria. Thus, several strategies can be used to stimulate the proliferation of these beneficial intestinal bacteria, being one of them the consumption of prebiotics. The development of new prebiotics, with added functionality, is one of the most serious challenges shared not only by the scientific community but also by the food industry. The objective of this work was to evaluate the potential prebiotic effect of red and white grape residues, both obtained during the winemaking process. For such purpose, an in vitro study with pure cultures of Lactobacillus and Bifidobacterium was first conducted. Secondly, a study with mixed cultures using human fecal inocula was carried out in a simulator of the distal part of the colon. The obtained results showed an increase in the Lactobacillus and Bifidobacterium population, indicating that these ingredients are serious candidates to be considered as prebiotics.



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Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition

Abstract

To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and cultured. The expressions of fibrosis related factors (α-SMA and collagen I), as well as ER stress markers (CHOP and GRP78) were determined by both real-time PCR assay and Western blotting, while the expressions of other ER stress signaling pathway factors PERK, IRE-1, ATF-6 and protein levels of caspase-12, caspase-9, caspase-3, PARP were determined by Western blotting. RLE-6TN cell line induced by TGF-β1 was also used to verify the amelioration effects in vitro study. In both in vivo and in vitro studies, TUNEL staining was used to evaluate cell apoptosis. Expressions of collagen I, α-SMA, GRP78, and CHOP were significantly inhibited by chlorogenic acid in dose-dependent manner. Similarly, decreasing levels of cleaved caspase-12, caspase-9, caspase-3 and increasing level of uncleaved PARP were observed in chlorogenic acid groups compared with those in the fibrosis group both in vivo and in vitro. Chlorogenic acid could also significantly down-regulate the level of phosphorylation of PERK and cleaved ATF-6 in vivo study. Moreover, MTT assay demonstrated chlorogenic acid could enhance proliferation of RLE-6TN cells induced by TGFβ1 in vitro. And the apoptosis assays indicated that chlorogenic acid could significantly inhibit cell apoptosis both in vivo and in vitro studies. Chlorogenic acid could inhibit the pulmonary fibrosis through endoplasmic reticulum stress inhibition in vivo and in vitro.



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This is The Most Powerful Natural Antibiotic Ever – Kills Any Infections in The Body - All India Roundup


All India Roundup

This is The Most Powerful Natural Antibiotic Ever – Kills Any Infections in The Body
All India Roundup
... headache to cancer make it rather special. Ginger is also a good regulator of asthma and can help lower the high blood pressure. It has been used as a natural remedy since ages. Horseradish is a powerful herb, efficient for treatments of sinuses ...



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Regulation of the Immune System by Laminins

Publication date: Available online 3 July 2017
Source:Trends in Immunology
Author(s): Thomas Simon, Jonathan S. Bromberg
Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. Finally, the role of the laminins in autoimmune diseases and transplantation will be discussed.



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Mucosal Bioengineering: Gut in a Dish

Publication date: Available online 3 July 2017
Source:Trends in Immunology
Author(s): Ivaylo I. Ivanov
Studying the interactions between commensal microbes and host intestinal tissue networks is challenging due to the complexity and inaccessibility of the system. A recent study reports a novel organ culture system that will enhance our ability to dissect these interactions.



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World Head and Neck Cancer Day: How a small spot turned deadly - Stuff.co.nz


Stuff.co.nz

World Head and Neck Cancer Day: How a small spot turned deadly
Stuff.co.nz
The death of her partner Fred Whittaker from mouth cancer has prompted Olwen Williams to urge others to seek medical help sooner. Even after the spot on his tongue was diagnosed as cancerous, Fred Whittaker never thought about dying. Then came the ...



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Production of Functional Inulin-Type Fructooligosaccharides by an Enzyme from Penicillium citrinum

Abstract

We report the production of functional inulin-type fructooligosaccharides such as trisaccharide 1-kestose, O–β-d-fructofuranosyl-(2→1)-β-d-fructofuranosyl α-d-glucopyranoside, and tetrasaccharide nystose, O-β-d-fructofuranosyl-(2→1)–β-d-fructofuranosyl-(2→1)–β-d-fructofuranosyl α-d-glucopyranoside, from sucrose by an enzyme from Penicillium citrinum. Sucrose acted as a fructosyl donor and acceptor for the enzyme. The optimum pH and temperature for the enzymatic reaction were 5 and 50 °C, respectively. The enzyme was stable in the pH range of 4.5–7 and at 50 °C. The maximum concentration of 1-kestose obtained was 110 mg/ml, and the maximum production efficiency was 37.3% after a 48-h reaction. The maximum efficiency of combined fructooligosaccharide (1-kestose and nystose) production was 47.1% after a 72-h reaction. Fructooligosaccharides were therefore successfully produced via a fructosyl transfer reaction catalyzed by an enzyme from P. citrinum.



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Turkish Stream, dossier verrà discusso da Putin con Erdogan ma anche con Juncker - Sputnik Italia


Sputnik Italia

Turkish Stream, dossier verrà discusso da Putin con Erdogan ma anche con Juncker
Sputnik Italia
Lo ha riferito uno dei più stretti collaboratori del presidente Putin, Yuri Ushakov che ha sottolineato i recenti progressi fatti dalle parti rispetto ad entrambi i dossier. Del gasdotto Turkish Stream Putin parlerà anche con il presidente della ...

and more »


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Emergy-based environmental accounting toward a sustainable Mongolia

Abstract

An emergy-based environmental accounting of Mongolia is presented based on the data from 1995 to 2012. By calculating natural and economic inputs and a series of emergy indicators, this paper discusses Mongolia's resource use structure, economic situation, trade status and societal sustainability. The results show that the total emergy use for Mongolia changed from 2.83×1022 sej in 1995 to 4.96×1022 sej in 2012, representing a 75% increase over the 18 years of this study, yet its emergy per capita remains one of the lowest in the world (1.74×1016 sej/capita). The emergy money ratio (EMR) of Mongolia during 1995–2012 decreased from 1.99×1013 sej/USD to 7.75×1012 sej/USD, which indicates that the power of a dollar for purchasing real wealth in Mongolia was declining, while the relatively high absolute values compared to its trading partners and even the world average EMR suggests that Mongolia is continuing a trade disadvantage. Mongolia's emergy exchange ratio is increasingly less than one to the point that in 2012 the ratio was 0.3 suggesting that the exported emergy was over 3.3 times greater than the imported emergy. The growing dependence on imports and the dramatic increase in exports suggests that Mongolia's economy is increasingly vulnerable to downturns in the world economy.



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Health-Related Quality of Life in Adults with Osteogenesis Imperfecta

Abstract

Osteogenesis imperfecta (OI) is a systemic connective tissue disorder most often caused by mutations in collagen type 1 related genes. Patients with OI suffer from multiple fractures and various degrees of growth deficiency and bone deformity. It is unknown whether the systemic effect of defect collagen type 1 influences the quality of life in patients with OI. We therefore aimed to investigate health-related quality of life (HRQoL) in a well-characterized cohort of adult patients with OI. We included 85 adult patients with mild to severe OI (types I, III, and IV) and obtained information about skeletal- and non-skeletal phenotypes and patient demographics. We investigated physical and mental HRQoL using a validated questionnaire, SF-36, and compared the data to values obtained in a population without OI. Patients with mild, moderate, and severe OI all had lower mean scores on domains describing physical HRQoL and a lower mean physical component score compared to the general population, p < 0.001. Patients with severe OI had lower mean scores on physical HRQoL, p < 0.05. The scores on domains reflecting mental HRQoL were more inhomogenously affected, but did not differ significantly from the general population. OI has an impact on physical and some aspects of mental HRQoL. The scores on physical health were correlated to severity of the OI disease. The mental component score in the OI patients was unaffected and comparable with the general population.



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UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression

Uridine 5′-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal ti...

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A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506)

In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective...

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Risk stratification system to predict recurrence of intrahepatic cholangiocarcinoma after hepatic resection

Previous nomograms for intrahepatic cholangiocarcinoma (ICC) were conducted to predict overall survival, which could be influenced by various factors. Herein, we conducted our nomogram to predict recurrence of...

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A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number ...

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Rural restructuring in China: Theory, approaches and research prospect

Abstract

Rural restructuring is a process of reshaping socio-economic morphology and spatial pattern in rural territory in response to the changes of elements both in kernel system and external system of rural development, by optimally allocating and efficiently managing the material and non-material elements in the two systems. It aims at ultimately optimizing the structure and promoting the function within rural territorial system as well as realizing the coordination of structure and complementation of function between urban and rural territorial system. This paper establishes a theoretical framework of rural restructuring through elaborating the concept and connotations as well as analyzing the mechanism pushing forward rural restructuring based on the evolution of "elements-structure-function", and probes the approaches from the three aspects of spatial restructuring, economic restructuring and social restructuring. Besides, the authors argue that the study of rural restructuring in China in the future needs to focus on the aspects of long-term and multi-scale process and pattern, mechanism, regional models, rural planning technology system and standard, policy and institutional innovations concerning rural restructuring as well as the impacts of globalization on rural restructuring, in order to serve the current national strategic demands and cope with the changes of rural development elements in the process of urban-rural development transformation.



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A review of Geographical Dynamics and Firm Spatial Strategy in China by Shengjun Zhu, John Pickles and Canfei He



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Reconstruction of cropland spatial patterns and its spatiotemporal changes over the 20th century on the Songnen Plain, Northeast China

Abstract

We initially estimated the cropland area at county level using local historical documents for the Songnen Plain (SNP) in the 1910s and 1930s. We then allocated this cropland area to grid cells with a size of 1 km × 1 km, using a range of cultivation possibilities from high to low; this was based on topography and minimum distances to rivers, settlements, and traffic lines. Cropland areas for the 1950s were obtained from the Land Use Map of Northeast China, and map vectorization was performed with ArcGIS technology. Cropland areas for the 1970s, 1980s, 1990s, 2000s, and 2010s were retrieved from Landsat images. We found that the cropland areas were 4.92 × 104 km2 and 7.60 × 104 km2, accounting for 22.8% and 35.2% of the total area of the SNP in the 1910s and 1930s, respectively, which increased to 13.14 × 104 km2, accounting for 60.9% in the 2010s. The cropland increased at a rate of 1.18 × 104 km2 per decade from the 1910s to 1970s while it was merely 0.285 × 104 km2 per decade from the 1970s to 2010s. From the 1910s to 1930s, new cultivation mainly occurred in the central SNP while, from the 1930s to 1970s, it was mainly over the western and northern parts. This spatially explicit reconstruction could be offered as primary data for studying the effects of changes in human-induced land cover based on climate change over the last century.



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The mechanism of barrier river reaches in the middle and lower Yangtze River

Abstract

Alluvial channel has always adjusted itself to the equilibrium state of sediment transport after it was artificially or naturally disturbed. How to maintain the equilibrium state of sediment transport and keep the river regime stable has always been the concerns of fluvial geomorphologists. The channel in the middle and lower reaches of the Yangtze River is characterized by the staggered distribution of the bifurcated river and the single-thread river. The change of river regime is more violently in the bifurcated river than in the single-thread river. Whether the adjustment of the river regime in the bifurcated river can pass through the single-thread river and propagate to the downstream reaches affects the stabilities of the overall river regime. Studies show that the barrier river reach can block the upstream channel adjustment from propagating to the downstream reaches; therefore, it plays a key role in stabilizing the river regime. This study investigates 34 single-thread river reaches in the middle and lower reaches of the Yangtze River. On the basis of the systematic summarization of the fluvial process of the middle and lower reaches of the Yangtze River, the control factors of barrier river reach are summarized and extracted: the planar morphology of single-thread and meandering; with no flow deflecting node distributed in the upper or middle part of the river reach; the hydraulic geometric coefficient is less than 4; the longitudinal gradient is greater than 12‰, the clay content of the concave bank is greater than 9.5%, and the median diameter of the bed sediment is greater than 0.158 mm. From the Navier-Stokes equation, the calculation formula of the bending radius of flow dynamic axis is deduced, and then the roles of these control factors on restricting the migration of the flow dynamic axis and the formation of the barrier river reach are analyzed. The barrier river reach is considered as such when the ratio of the migration force of the flow dynamic axis to the constraint force of the channel boundary is less than 1 under different flow levels. The mechanism of the barrier river reach is such that even when the upstream river regime adjusts, the channel boundary of this reach can always constrain the migration amplitude of the flow dynamic axis and centralize the planar position of the main stream line under different upstream river regime conditions, providing a relatively stable incoming flow conditions for the downstream reaches, thereby blocking the upstream river regime adjustment from propagating to the downstream reaches.



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Interacting effects of multiple factors on the morphological evolution of the meandering reaches downstream the Three Gorges Dam

Abstract

Elucidating the influence of dams on fluvial processes can inform river protection and basin management. However, relatively few studies have focused on how multiple factors interact to affect the morphological evolution of meandering reaches. Using hydrological and topographical data, we analyzed the factors that influence and regulate the meandering reaches downstream the Three Gorges Dam (TGD). Our conclusions are as follows. (1) The meandering reaches can be classified into two types based on their evolution during the pre-dam period: G1 reaches, characterized by convex point bar erosion and concave channel deposition (CECD), and G2 reaches, characterized by convex point bar deposition and concave channel erosion (CDCE). Both reach types exhibited CECD features during the post-dam period. (2) Flow processes and sediment transport are the factors that caused serious erosion of the low beaches located in the convex point bars. However, changes in the river regime, river boundaries and jacking of Dongting Lake do not act as primary controls on the morphological evolution of the meandering reaches. (3) Flood discharges ranging from 20,000 to 25,000 m3/s result in greater erosion of convex point bars. The point bars become scoured if the durations of these flows, which are close to bankfull discharge, exceed 20 days. In addition, the reduction in bedload causes the decreasing of point bar siltation in the water-falling period. (4) During the post-dam period, flood abatement, the increased duration of discharges ranging from 20,000 to 25,000 m3/s, and a significant reduction in sediment transport are the main factors that caused meandering reaches to show CECD features. Our results are relevant to other meandering reaches, where they can inform estimates of riverbed change, river management strategies and river protection.



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The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma

Abstract

Autophagy is a life phenomenon in which autophagosomes remove damaged or aging organelles and long-lived circulating proteins to maintain the cell's stability. However, disorders of excessive autophagy are a response of cancer cells to a variety of anticancer treatments which lead to cancer cell death. The Akt/mammalian target of rapamycin (mTOR) and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways are both involved in nutrient-induced autophagic phenomenon and exhibit vital relevance to oncogenesis in various cancer cell types, including hepatocellular carcinoma (HCC). However, the influence of autophagy for cancer cell death remains controversial and few scientists have investigated the variation of these two signaling pathways in cancer cell autophagic phenomenon induced by anticancer treatment simultaneously. Here, we explored the anticancer efficacy and mechanisms of glycyrrhizin (GL), a bioactive compound of licorice with little toxicity in normal cells. It is interesting that inhibition of Akt/mTOR signaling in concurrence with enhanced ERK1/2 activity exists in GL-induced autophagy and cytotoxicity in HepG2 and MHCC97-H hepatocellular carcinoma cells. These results imply that the GL-related anticancer ability might correlate with the induction of autophagy. The influence of induced autophagic phenomenon on cell viability might depend on the severity of autophagy and be pathway specific. In the subsequent subcutaneous xenograft experiment in vivo with MHCC97-H cells, GL obviously exhibited its inhibitory efficacy in tumor growth via inducing excess autophagy in MHCC97-H cells (P < 0.05). Our data prompt that GL possesses a property of excess autophagic phenomenon induction in HCC and exerts high anticancer efficacy in vitro and in vivo. This warrants further investigation toward possible clinical applications in patients with HCC.

Thumbnail image of graphical abstract

Glycyrrhizin can induce excessive autophagic phenomenon in hepatocellular carcinoma cell lines. Autophagy-mediated cell death is also a credible route of tumor suppression pathway.



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Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations

Abstract

Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed to achieve effective therapy for patients with EGFR mutation L858R or nonsquamous histology.

Thumbnail image of graphical abstract

First-line with maintenance therapies have shown benefits in selected advanced NSCLC populations. Here, first-line with maintenance treatments are compared within patient groups and clinically meaningful benefits are shown for particular first-line with maintenance therapies in selected patients.



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Index case

Index case: A person who first draws attention to his or her family because of having a medical condition. For example, if an eye doctor discovers a person has glaucoma, and subsequently other cases of glaucoma are found in the person's family, that person is the index case. Also known as propositus (if male) or proposita (if female).



MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Development and application of a perioral force measurement system for infants with cleft lip and palate

As muscles converge or intermingle around the perioral area, and it change by the sequential therapy for cleft lip and palate (CLP) infants. The force of perioral muscles has a great influence on maxillary development and morphology. Perioral force in CLP infants has not been well studied, and accurate and reliable measurement of perioral force in infants remains a challenge. The aim of this study was to investigate a new way to accurately and reliably measure perioral force in UCLP infants and explore the change before and after cheiloplasty.

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Innate function of house dust mite allergens: robust enzymatic degradation of extracellular matrix at elevated pH

Exposure to the house dust mite Dermatophagoides pteronyssinus (D.p.) increases the risk for developing allergic diseases in humans and their best friends, the dogs. Here, we explored whether this allergenic mite...

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Incidental findings on cerebral MRI in twins: the Older Australian Twins Study

Abstract

Incidental findings on structural cerebral magnetic resonance imaging (MRI) are common in healthy subjects, and the prevalence increases with age. There is a paucity of data regarding incidental cerebral findings in twins. We examined brain MRI data acquired from community-dwelling older twins to determine the prevalence and concordance of incidental cerebral findings, as well as the associated clinical implications. Participants (n = 400) were drawn from the Older Australian Twins Study. T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) cerebral MRI scans were systematically reviewed by a trained, blinded clinician. Incidental findings were recorded according to pre-determined categories, and the diagnosis confirmed by an experienced neuroradiologist. Periventricular and deep white matter hyperintensities (WMH) were scored visually. WMH heritability was calculated for those with the twin pair included in the study (n = 320 individuals; monozygotic (MZ) = 92 twin pairs, dizygotic (DZ) = 68 twin pairs). Excluding infarcts and WMH, a total of 47 (11.75%) incidental abnormalities were detected. The most common findings were hyperostosis frontalis interna (8 participants; 2%), meningiomas, (6 participants; 1.5%), and intracranial lipomas (5 participants; 1.25%). Only 3% of participants were referred for follow-up. Four twin pairs, all monozygotic, had lesions concordant with their twin. Periventricular WMH was moderately heritable (0.61, CI 0.43–0.75, p = 7.21E-08) and deep WMH highly heritable (0.80, CI 0.66–0.88, p = 1.76E-13). As in the general population, incidental findings on cerebral MRI in older twins are common, although concordance rates are low. Such findings can alter the clinical outcome of participants, and should be anticipated by researchers when designing trials involving cerebral imaging.



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The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer: a meta-analysis with 6051 cases - Dove Medical Press


The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer: a meta-analysis with 6051 cases
Dove Medical Press
The pooled sensitivity of Ki-67/MIB-1 was 0.61 (95% confidence interval [CI]: 0.59–0.63) and specificity was 0.75 (95% CI: 0.74–0.77) in thyroid cancer. The pooled positive likelihood ratio was 3.19 (95% CI: 2.30–4.42) and negative likelihood ratio was ...



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Functional connectivity density mapping: comparing multiband and conventional EPI protocols

Abstract

Functional connectivity density mapping (FCDM) is a newly developed data-driven technique that quantifies the number of local and global functional connections for each voxel in the brain. In this study, we evaluated reproducibility, sensitivity, and specificity of both local functional connectivity density (lFCD) and global functional connectivity density (gFCD). We compared these metrics using the human connectome project (HCP) compatible high-resolution (2 mm isotropic, TR = 0.8 s) multiband (MB), and more typical, lower resolution (3.5 mm isotropic, TR = 2.0 s) single-band (SB) resting state functional MRI (rs-fMRI) acquisitions. Furthermore, in order to be more clinically feasible, only rs-fMRI scans that lasted seven minutes were tested. Subjects were scanned twice within a two-week span. We found sensitivity and specificity increased and reproducibility either increased or did not change for the MB compared to the SB acquisitions. The MB scans also showed improved gray matter/white matter contrast compared to the SB scans. The lFCD and gFCD patterns were similar across MB and SB scans and confined predominantly to gray matter. We also observed a strong spatial correlation of FCD between MB and SB scans indicating the two acquisitions provide similar information. These findings indicate high-resolution MB acquisitions improve the quality of FCD data, and seven minute rs-fMRI scan can provide robust FCD measurements.



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World Head and Neck Cancer Day: How a small spot turned deadly - Stuff.co.nz


Stuff.co.nz

World Head and Neck Cancer Day: How a small spot turned deadly
Stuff.co.nz
She was a passionate supporter of the Head and Neck Cancer Survivors' Support Network and advocated for better care and outcomes for people with head and neck cancer. "If you've got something that just won't heal then serious questions need to be ...



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Complications after long-term inferior vena cava filter placement [Practice]



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The new medical model: why medicine needs philosophy [Letters]



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Type 2 diabetes in a four-year-old child [Practice]



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Drug pricing reforms promising but problematic [News]



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Priority reviews: innovation and safety [Letters]



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Impact of the North American Free Trade Agreement on high-fructose corn syrup supply in Canada: a natural experiment using synthetic control methods [Research]

BACKGROUND:

Critics of free trade agreements have argued that they threaten public health, as they eliminate barriers to trade in potentially harmful products, such as sugar. Here we analyze the North American Free Trade Agreement (NAFTA), testing the hypothesis that lowering tariffs on food and beverage syrups that contain high-fructose corn syrup (HFCS) increased its use in foods consumed in Canada.

METHODS:

We used supply data from the Food and Agriculture Organization of the United Nations to assess changes in supply of caloric sweeteners including HFCS after NAFTA. We estimate the impact of NAFTA on supply of HFCS in Canada using an innovative, quasi-experimental methodology — synthetic control methods — that creates a control group with which to compare Canada's outcomes. Additional robustness tests were performed for sample, control groups and model specification.

RESULTS:

Tariff reductions in NAFTA coincided with a 41.6 (95% confidence interval 25.1 to 58.2) kilocalorie per capita daily increase in the supply of caloric sweeteners including HFCS. This change was not observed in the control groups, including Australia and the United Kingdom, as well as a composite control of 16 countries. Results were robust to placebo tests and additional sensitivity analyses.

INTERPRETATION:

NAFTA was strongly associated with a marked rise in HFCS supply and likely consumption in Canada. Our study provides evidence that even a seemingly modest change to product tariffs in free trade agreements can substantially alter population-wide dietary behaviour and exposure to risk factors.



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The "new" medical model, fragmented clinical care and philosophy of medicine [Letters]



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Trade and public health [Commentary]



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Testing for heritable thrombophilia in acute venous thromboembolism [Practice]



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Fewer Canadian MDs heading to the US [News]



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Johns Hopkins: A Canadian medical school? [Humanities]



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Ukrainians battle escalating HIV epidemic [News]



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Diabetes and Wound Angiogenesis

IJMS, Vol. 18, Pages 1419: Diabetes Mellitus Type II (DM2) is a growing international health concern with no end in sight. Complications of DM2 involve a myriad of comorbidities including the serious complications of poor wound healing, chronic ulceration, and resultant limb amputation. In skin wound healing, which has definite, orderly phases, diabetes leads to improper function at all stages. While the etiology of chronic, non-healing diabetic wounds is multi-faceted, the progression to a non-healing phenotype is closely linked to poor vascular networks. This review focuses on diabetic wound healing, paying special attention to the aberrations that have been described in the proliferative, remodeling, and maturation phases of wound angiogenesis. Additionally, this review considers therapeutics that may offer promise to better wound healing outcomes.




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TGF-β induced PAR-1 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone

TGF-β induced PAR-1 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone:

Abstract

Although protease activated receptor-1 (PAR-1) has been confirmed as an oncogene in many cancers, the role of PAR-1 in giant cell tumor (GCT) of bone has been rarely reported. The mechanism of PAR-1 in tumor-induced osteoclastogenesis still remains unclear. In the present study, we detected that PAR-1 was significantly upregulated in GCT of bone compared to normal tissues, while TGF-β was also overexpressed in GCT tissues and could promote the expression of PAR-1 in a dose and time dependent manner. By using the luciferase reporter assay, we found that two downstreams of TGF-β, Smad3 and Smad4, could activate the promoter of PAR-1, which might explain the mechanism of TGF-β induced PAR-1 expression. Meanwhile, PAR-1 was also overexpressed in microvesicles from stromal cells of GCT (GCTSCs), and might be transported from GCTSCs to monocytes through microvesicles. In addition, knockout of PAR-1 by TALENs in GCTSCs inhibited tumor growth, angiogenesis and osteoclastogenesis in GCT in vitro. By using the chick CAM models, we further showed that inhibition of PAR-1 suppressed tumor growth and giant cell formation in vivo. By using microarray assay, we detected a number of genes involved in osteoclastogenesis as the possible downstreams of PAR-1, which may partly explain the mechanism of PAR-1 in GCT. In brief, for the first time, these results reveal an upstream regulatory role of TGF-β in PAR-1 expression, and PAR-1 expression promotes tumor growth, angiogenesis and osteoclast differentiation in GCT of bone. Hence, PAR-1 represents a novel potential therapeutic target for GCT of bone. This article is protected by copyright. All rights reserved.


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Ventilator-Associated Pneumonia in Critically Ill Children

Children, Vol. 4, Pages 56: Incidence of Ventilator-Associated Pneumonia in Critically Ill Children Undergoing Mechanical Ventilation in Pediatric Intensive Care Unit: Background: Among hospital-acquired infections (HAIs) in children, ventilator-associated pneumonia (VAP) is the most common after blood stream infection (BSI). VAP can prolong length of ventilation and hospitalization, increase mortality rate, and directly change a patient's outcome in Pediatric Intensive Care Units (PICU). Objectives: The research on VAP in children is limited, especially in Iran; therefore, the identification of VAP incidence and mortality rate will be important for both clinical and epidemiological implications. Materials and Methods: Mechanically ventilated pediatric patients were assessed for development of VAP during hospital course on the basis of clinical, laboratory and imaging criteria. We matched VAP group with control group for assessment of VAP related mortality in the critically ill ventilated children. Results: VAP developed in 22.9% of critically ill children undergoing mechanical ventilation. Early VAP and late VAP were found in 19.3% and 8.4% of VAP cases, respectively. Among the known VAP risk factors that were investigated, immunodeficiency was significantly greater in the VAP group (p = 0.014). No significant differences were found between the two groups regarding use of corticosteroids, antibiotics, PH (potential of hydrogen) modifying agents (such as ranitidine or pantoprazole), presence of nasogastric tube and total or partial parenteral nutrition administration. A substantial number of patients in the VAP group had more than four risk factors for development of VAP, compared to those without VAP (p = 0.087). Mortality rate was not statistically different between the VAP and control groups (p = 0.477). Conclusion: VAP is still one of the major causes of mortality in PICUs. It is found that altered immune status is a significant risk factor for acquiring VAP. Also, occurrence of VAP was high in the first week after admission in PICU.




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Delaying lymph node biopsy after melanoma diagnosis does not affect survival rates

Delaying lymph node biopsy after melanoma diagnosis does not affect survival ratesPostponing lymph node biopsy more than 30 days after melanoma diagnosis doesn't adversely impact long-term clinical outcomes, according to new study findings published online on the Journal of the American College of Surgeons website ahead of print publication.

Every year, about 87,000 people are diagnosed with melanoma, according to the American Cancer Society.1 This most severe form of skin cancer is almost entirely curable if caught before it spreads to nearby (sentinel) lymph nodes.
Today, management of high-risk melanomas starts with surgical removal of the layers of skin cancer and a lymph node biopsy, a procedure in which a tissue sample is sent to a lab to check for cancerous cells. Patients with a positive sentinel node biopsy may undergo complete lymph node dissection to lower the risk of recurrence.
In theory, postponing biopsy after a melanoma diagnosis could affect outcomes, either in a negative way by allowing the growth and spread of cancerous cells to lymph nodes, or in a positive way by allowing development of an anti-melanoma immune response.
There have been small studies showing each of those scenarios, said study coauthor Mark Faries, MD, FACS, co-director of the melanoma program at The Angeles Clinic and Research Institute, Los Angeles, Calif. "We often get questions from patients as to whether or not they need to rush to have their operation performed when they are diagnosed with melanoma. So the question of whether waiting hurts or helps has never been clearly answered," Dr. Faries said. "We wanted to settle that controversy by looking at two very large data sets to see if there was an actual difference."
In this study, the largest one to date, researchers analyzed the effect of delayed sentinel lymph node biopsy on survival of patients with melanoma.
Dr. Faries and colleagues from the John Wayne Cancer Institute and elsewhere examined the medical records of 2,483 patients who underwent wide local excision and sentinel lymph node biopsy for melanoma skin cancer between 1999 and 2015. They analyzed whether lymph nodes biopsied later were associated with different outcomes, either positive or negative, compared to lymph nodes biopsied earlier. The average follow-up time was eight years.
Early and delayed sentinel-lymph node biopsy were defined as less than 30 days and more than 30 days from diagnosis, respectively. Primary outcomes included disease-free survival and melanoma-specific survival.
Of those 2,483 patients, positive sentinel lymph nodes were identified in 432 patients (17 percent). A majority of patients (58 percent) underwent early sentinel-lymph node biopsy. The study found no difference in melanoma-specific survival or disease-free survival in patients who underwent early or delayed sentinel lymph node biopsy. In other words, there was no harm or benefit in waiting 30 days or longer to have a lymph node biopsy.
An independent dataset from the first Multicenter Selective Lymphadenectomy Trial, a multicenter prospective randomized trial, was used to validate these findings. The exact same analysis showed similar results in survival outcomes.
cancer diagnosis impacts not only the body, but also the mind and emotions. Approximately one-third of patients diagnosed with melanoma report emotional challenges such as fear of death, anxiety, and uncertainty. However, it is important for people to understand that if their biopsy needs to be postponed by several weeks, they are still safe.
"When we talk to patients diagnosed with melanoma, the main rationale is to get the surgical procedure over and done with and get the information and resources they need so that they can move on," Dr. Faries said. "But people can be reassured that if they are in a situation where, for one reason or another, they need to wait to have an operation, that's okay too."
Article: Impact of Time Between Diagnosis and SLNB on Outcomes in Cutaneous Melanoma, Mark B. Faries et al., Journal of the American College of Surgeons, doi: 10.1016/j.jamcollsurg.2017.05.013, published online 28 June 2017.


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Stratifying HPV-positive women for CIN3+ risk after one and two rounds of HPV-based screening

Stratifying HPV-positive women for CIN3+ risk after one and two rounds of HPV-based screening:

Abstract

A main challenge of human papilloma (HPV)-based screening for cervical cancer is to adequately identify HPV-positive women at highest risk of cervical intraepithelial neoplasia grade 3 or worse, CIN3+. The prognostic value of currently used adjunct markers (HPV16/18 genotyping and reflex cytology) may change after multiple rounds of HPV-based screening because of a change in the proportion of HPV-positive women with incident infections. To this end, we re-analyzed results from the POBASCAM trial (Population Based Screening Study Amsterdam). Women were randomized to HPV/cytology co-testing (intervention group) or to cytology-only (HPV blinded; control group) at enrolment. Our analytical population consisted of women with an HPV-positive result at the second round, five years after enrolment (n=381 intervention, n=392 control). Nine-year CIN3+ risks were estimated by Kaplan Meier. HPV-positive women were stratified by risk markers: HPV16/18 genotyping, reflex cytology and preceding HPV results. When comparing one to two rounds of HPV-based screening, the prognostic value of an abnormal cytology result did not change (40.0% vs 42.3%, P=0.5617), but diminished for an HPV16/18 positive result (25.4% vs 38.0%, P=0.0132). HPV16/18 genotyping was non-discriminative in women with incident HPV infections (HPV16/18 positive 10.0% vs negative 12.1%, P=0.3193). Women from the intervention group were more likely to have incident infections compared to women from the control group (incident screen-positive results 75.6% vs 64.6%, P=0.001) Our results indicate that at a second round of HPV-based screening, risk differentiation by cytology remained strong, but was diminished for HPV 16/18 genotyping because of a larger proportion of incident infections. This article is protected by copyright. All rights reserved.


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Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic Maxillary Atelectasis

Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic Maxillary Atelectasis: Chronic maxillary atelectasis (CMA) is characterized by a progressive decrease in maxillary sinus volume. The factors that promote the stage progression of CMA remain poorly understood. Here, we describe the time course of anatomical changes in a 40-year-old woman with stage II CMA that progressed to stage III disease. She did not show stage progression until she started to develop repetitive sinus-related symptoms. The stage progression was characterized by ocular symptoms. The repetitive inflammatory episodes may have increased the negative pressure in the affected sinus and weakened the bone walls, thereby promoting stage progression. Thus, a history of repetitive sinus-related symptoms may be a risk factor for stage progression in CMA.




 (a) Facial appearance: the arrows in the right and left pictures indicate the superior sulcus. The right superior sulcus appears to be deeper than the left superior sulcus.
(b) Endoscopic findings: the right middle meatus is more enlarged than the left middle meatus.
(c) Axial and coronal views on computed tomography. 
(d) T1 and T2 weighted images on magnetic resonance imaging. The T1 axial image shows that the right medial wall of the maxillary sinus (shown by the arrow) deviates laterally. The T2 coronal image indicates inferior bowing of the inferior wall of the orbit (shown by the arrow). The T2 sagittal images show prominent deviation of the posterior wall in the right maxillary sinus (shown by the arrow in the right image) relative to the structure in the left maxillary sinus (left image). The red and blue lines in the T2 axial image indicate the distance from the center line to the most deviated medial wall of the maxillary sinus.
(a)
(b)
Figure 2: Magnetic resonance images taken 3 and 2 years before the development of ocular manifestations. (a) Magnetic resonance image (MRI) findings: (A) the T2 axial view of MRI 3 years before the ocular presentation; (B) the T2 axial view of MRI 2 years before the ocular presentation. Both images show that the medial wall of the right maxillary sinus is deviated compared to the medial wall of the left maxillary sinus. Similar anatomical changes are observed. Thus, 3 and 2 years before ocular manifestations appeared, the distances from the center line to the most deviated medial wall of the right maxillary sinus were 19 and 19 mm (red lines), respectively. By contrast, the distances from the center line to the most deviated medial wall of the left (unaffected) maxillary sinus were 11.5 and 11 mm (blue lines), respectively. Both situations indicate stage II disease. (b) Time course of the CMA patient. The first MRI was performed 3 years before ocular symptom presentation (A). The second MRI was performed 2 years before ocular symptom presentation (B). The patient did not present with any sinusitis-related symptoms before or at the first (A) and the second (B) MRI. However, in the 2 years following the second MRI, the patient frequently presented with sinus-related symptoms. At the end of that period, the patient was diagnosed with stage III disease.


(a)
(b)
(c)
Figure 3: Summary of the clinical examination after the endoscopic sinus surgery. (a) Facial appearance 6 months after the endoscopic sinus surgery (ESS). The arrows in the right and left pictures show the superior sulcus. The deepening of the right superior sulcus that was observed before the sinus surgery appeared to have been eliminated by the ESS. (b) Endoscopic findings 6 months after the ESS. The right uncinate process was removed and recurrence of the deformity was not observed. (c) Computed tomography findings 10 months after the ESS. The deviation of the posterior wall in the right maxillary sinus (shown by the arrow) seems to have been eliminated by the ESS.














  Case Reports in Otolaryngology
Volume 2017 (2017), Article ID 4296195, 5 pages
http://ift.tt/2tDSh1u
Case Report

Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic Maxillary Atelectasis

Department of Otolaryngology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Correspondence should be addressed to Shu Kikuta
Received 22 March 2017; Accepted 5 June 2017; Published 3 July 2017
Academic Editor: Marco Berlucchi
Copyright © 2017 Shu Kikuta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic maxillary atelectasis (CMA) is characterized by a progressive decrease in maxillary sinus volume. The factors that promote the stage progression of CMA remain poorly understood. Here, we describe the time course of anatomical changes in a 40-year-old woman with stage II CMA that progressed to stage III disease. She did not show stage progression until she started to develop repetitive sinus-related symptoms. The stage progression was characterized by ocular symptoms. The repetitive inflammatory episodes may have increased the negative pressure in the affected sinus and weakened the bone walls, thereby promoting stage progression. Thus, a history of repetitive sinus-related symptoms may be a risk factor for stage progression in CMA.

1. Introduction

Chronic maxillary atelectasis (CMA) is characterized by a persistent and progressive decrease in the maxillary sinus volume and occlusion of the infundibulum as a result of inward bowing of the antral walls [14]. CMA is categorized into three stages on the basis of the degree of sinus wall deformation. Stage I is characterized by a lateralized maxillary fontanel (membranous deformity); stage II is defined as inward bowing of one or more of the osseous walls (bone deformity); and stage III is characterized by enophthalmos, hypoglobus, and/or midfacial deformity (clinical deformity) [15]. Although several authors have previously reported cases of patients with CMA [269], they only described the condition at one time point. We speculated that if we followed CMA patients as they progressed through the various stages of CMA, we might be able to identify factors that predict stage progression. We report here the case of a patient with stage II CMA who did not exhibit progression until she developed repetitive sinus-related symptoms. This development might be associated with the progression of the disease to stage III CMA. Our observations suggest that a history of repetitive sinus-related symptoms may be a risk factor for stage progression in CMA.

2. Case Presentation

A 40-year-old Hungarian woman suddenly noticed upgaze diplopia and right cheek compression when she woke up in the morning. Shortly thereafter, she consulted an ophthalmologist and then an otolaryngologist in another hospital. The investigations suggested that she had a carcinoma in the pterygopalatine fossa on the right side. Therefore, the otolaryngologist referred the patient to our institution for further examination. Examination of the facial appearance of the patient indicated more deepening of the right upper eyelid sulcus than the left eyelid sulcus (Figure 1(a)). An endoscopic examination showed that the right uncinate process could not be clearly detected and seemed to adhere to the medial wall of the maxillary sinus (Figure 1(b)). Computed tomography (CT) imaging then revealed inferior bowing of the floor of the orbit into the right maxillary sinus, lateral drifting of the right uncinate process into close contact with the floor of the orbit, and partial opacification of the maxillary sinus and anterior ethmoidal cells (Figure 1(c)). Magnetic resonance imaging (MRI) findings confirmed prolapse of the inferior inward retraction of the posterior, lateral, and medial walls of the maxillary sinus on the right side (Figure 1(d)). The patient had not experienced any trauma and did not have any endocrinological problems, developmental anomalies, and/or systemic diseases such as Wegener granulomatosis, orbital metastasis, osteomyelitis, progressive lipodystrophy, or facial hemiatrophy. The possibility of carcinoma in the pterygopalatine fossa was excluded by a FDG-positron emission tomography study. On the basis of these findings, the patient was diagnosed with stage III CMA.
Figure 1: Summary of the clinical examination at the time the patient presented at our hospital. (a) Facial appearance: the arrows in the right and left pictures indicate the superior sulcus. The right superior sulcus appears to be deeper than the left superior sulcus. (b) Endoscopic findings: the right middle meatus is more enlarged than the left middle meatus. (c) Axial and coronal views on computed tomography. (d) T1 and T2 weighted images on magnetic resonance imaging. The T1 axial image shows that the right medial wall of the maxillary sinus (shown by the arrow) deviates laterally. The T2 coronal image indicates inferior bowing of the inferior wall of the orbit (shown by the arrow). The T2 sagittal images show prominent deviation of the posterior wall in the right maxillary sinus (shown by the arrow in the right image) relative to the structure in the left maxillary sinus (left image). The red and blue lines in the T2 axial image indicate the distance from the center line to the most deviated medial wall of the maxillary sinus.
Three years before the onset of the upgaze diplopia and right cheek compression, the patient had undergone brain MRI screening for a lacunar infarction. She had not previously presented with symptoms related to the nose or sinuses. When we reviewed these MRI images, we observed mucosal hyperplasia of the maxillary sinus and deviation of the medial wall of the maxillary sinus on the right side (as compared to the contralateral unaffected side). Thus, we retrospectively diagnosed the patient with stage II CMA. As shown by Figure 2(a), at that time point, the distance from the center line (defined as the line from the center of the midbrain to the nose tip) to the most deviated medial wall of the maxillary sinus was 19 mm on the right side (red line in (A)) and 11.5 mm on the left side (blue line in (A)).
Figure 2: Magnetic resonance images taken 3 and 2 years before the development of ocular manifestations. (a) Magnetic resonance image (MRI) findings: (A) the T2 axial view of MRI 3 years before the ocular presentation; (B) the T2 axial view of MRI 2 years before the ocular presentation. Both images show that the medial wall of the right maxillary sinus is deviated compared to the medial wall of the left maxillary sinus. Similar anatomical changes are observed. Thus, 3 and 2 years before ocular manifestations appeared, the distances from the center line to the most deviated medial wall of the right maxillary sinus were 19 and 19 mm (red lines), respectively. By contrast, the distances from the center line to the most deviated medial wall of the left (unaffected) maxillary sinus were 11.5 and 11 mm (blue lines), respectively. Both situations indicate stage II disease. (b) Time course of the CMA patient. The first MRI was performed 3 years before ocular symptom presentation (A). The second MRI was performed 2 years before ocular symptom presentation (B). The patient did not present with any sinusitis-related symptoms before or at the first (A) and the second (B) MRI. However, in the 2 years following the second MRI, the patient frequently presented with sinus-related symptoms. At the end of that period, the patient was diagnosed with stage III disease.
Two years before the clinical onset of CMA, the patient underwent follow-up MR imaging. As shown by Figure2(a), retrieval and retrospective examination of these images indicated that the anatomical deformity in the right maxillary sinus had not progressed (the red and blue lines in (B) indicated distances from the center line of 19 and 11 mm, resp.).
In the 2 years after the second MRI, the patient started complaining of repeated sinus-related symptoms such as cheek pain or pressure on both sides and anterior purulent nasal discharge once every 1 or 2 months (Figure2(b)). She frequently consulted private Ear, Nose, and Throat Clinics to address these issues but was told it was due to sinusitis. At each visit, the patient was prescribed with a week-long course of antibiotics. Two years after the second MRI, the patient developed the ophthalmological symptoms, was referred to our hospital, and was diagnosed with stage III CMA (Figure 2(b)).
To treat the ocular symptoms, we used endoscopic sinus surgery (ESS) to eliminate the negative pressure within the maxillary sinus. We removed the laterally drifted uncinate process that was in close contact with the floor of the orbit and observed mucosal hypertrophy of the maxillary sinus. Pathology of the mucosae in the maxillary sinus revealed infiltration with inflammatory cells. After the treatment, the ocular symptoms of the patients disappeared rapidly.
After surgery, we regularly followed the patient by endoscopy and CT imaging for more than 1 year. Six months after the ESS, right enophthalmos seemed to be equivalent to that on the affected side (Figure 3(a), arrow) and endoscopy showed that there was no recurrence of the nasal deformity (Figure 3(b)). Ten months after the ESS, CT imaging showed that the anatomical deformity of the posterior wall in the maxillary sinus had been repaired (Figure 3(c), arrow).
Figure 3: Summary of the clinical examination after the endoscopic sinus surgery. (a) Facial appearance 6 months after the endoscopic sinus surgery (ESS). The arrows in the right and left pictures show the superior sulcus. The deepening of the right superior sulcus that was observed before the sinus surgery appeared to have been eliminated by the ESS. (b) Endoscopic findings 6 months after the ESS. The right uncinate process was removed and recurrence of the deformity was not observed. (c) Computed tomography findings 10 months after the ESS. The deviation of the posterior wall in the right maxillary sinus (shown by the arrow) seems to have been eliminated by the ESS.

3. Discussion

We were able to observe the anatomical changes in our CMA patient as she progressed from stage II to stage III CMA over a period of 3 years. The progression of the condition appeared to be associated with the development of repeated sinus-related symptoms over 2 years. These symptoms preceded the development of the ocular symptoms that led to the diagnosis of stage III CMA. These observations suggest that a history of repetitive sinus-related symptoms may indicate progression of the anatomical deformity in CMA. As described below, these symptoms may be indicative of processes that promote CMA progression.
Occluded maxillary infundibulum produces an enclosed hypoventilated environment in the maxillary sinus [10,11]. This enclosed cavity also induces air reabsorption within the affected sinus, which creates additional negative pressure. This leads to the eventual collapse of the maxillary sinus [12]. We speculate that the development of negative pressure in the affected sinus may also be further promoted by bacteria-induced inflammation of the mucosae in the occluded maxillary sinus, which enriches the capillary network of the sinus mucosae and increases the absorption of respiratory gases [1315]. Moreover, repeated severe inflammatory changes in the mucosa may also induce immunological bone catabolism that causes thinning and demineralization of the bony wall [7]. Thus, we propose that a history of repetitive severe sinus inflammation that is accompanied by nasal symptoms may reflect promotion of negative pressure within the maxillary sinus and inflammation that weakens the bony wall. These processes ultimately cause the bony wall to bow inwardly, thus leading to stage progression in the CMA patient. We cannot rule out the possibility that negative pressure on its own is the key cause of stage progression in CMA. Nevertheless, our case suggests that the repetitive severe sinus inflammation may further facilitate the pathological consequences of the negative pressure within the maxillary sinus and therefore promote the collapse of the vulnerable bony wall.
It has been reported that some patients in the advanced stage have persistent ocular complaints after the negative pressure is removed by sinus surgery [1617]. This suggests that it may be necessary to remove the negative pressure while the CMA is at an early stage. This approach is further supported by our case, which suggests that patients who frequently experience sinus-related symptoms might be required to undergo sinus surgery to prevent further stage progression.

4. Conclusion

Our CMA patient had a history of repetitive sinus-related symptoms for 2 years before clinical and MRI evidence indicated that the CMA had progressed from stage II to stage III. Thus, a history of repetitive severe inflammation that is accompanied with sinus-related symptoms such as cheek pain or pressure and purulent nasal discharge may associate with stage progression of CMA. Early sinus surgery may prevent CMA stage progression and could be required if the patient frequently experiences sinus-related symptoms.

Ethical Approval

This study was reviewed and approved by the Institutional Review Board of the University of Tokyo Hospital (#2487). The requirement for informed consent was waived. The investigation of this case was conducted according to the principles of the Declaration of Helsinki and its revisions.

Conflicts of Interest

The authors report no conflicts of interest.

Authors' Contributions

Shu Kikuta and Kyohei Horikiri contributed equally to the work.

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