Molecular species of prostaglandins involved in modulating luteinising hormone pulses of female rats under infectious stress conditions.

Abstract: Mammalian reproductive function is controlled by the hypothalamic-pituitary-gonadal (HPG) axis, which is suppressed under infectious stress conditions. By analysing the pulsatility of luteinising hormone (LH), we have previously demonstrated that prostaglandins (PGs) in the central nervous system mediate infectious stress to suppress the activity of the HPG axis. The present study aimed to characterise the types of PGs responsible for suppression of the HPG axis. We focused on three major types of PGs: PGE2 , PGD2 and PGF2α . We used female rats overiectomised bilaterally 1 week before the experiments. Lipopolysaccharide (100 μg kg-1 ) suppressed LH pulses at the same time as enhancing the concentration of all three PGs in the cerebrospinal fluid, which was restored by indomethacin (10 mg kg-1 ). Subsequently, we observed LH pulsatility after a single injection of each PG and after co-injection of PGE2 with PGF2α into the third cerebral ventricle. A single injection of PGE2 dose-dependently induced a transient increase in mean LH concentration and LH pulse amplitude, and PGD2 significantly increased the amplitude of LH pulses, wereas PGF2α did not affect LH pulsatility. On the other hand, co-injection of PGE2 and PGF2α induced a significant suppression of both the frequency and amplitude of LH pulses. These results suggest that PGE2 and PGF2α can represent two of the mediators that suppress the HPG axis in situations of infectious stress. Moreover, the results imply that there are two contradictory effects of PGE2 on LH pulsatility: (i) enhancive when working alone and (ii) suppressive when working together with PGF2α .

Matsuwaki|T|T|0000-0002-4842-6110 Komatsuda|M|M| Fujisawa|A|A| Doke|M|M| Yamanouchi|K|K| Nishihara|M|M|


Potential treatments for food allergy.

Abstract: This article presents an overview of potential treatments of food allergy, with an emphasis on various forms of immunotherapy (including oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, immunotherapy with modified food antigens, and immunotherapy with a recombinant peanut vaccine). Allergen nonspecific treatments, such as Chinese herbal formulas, probiotics/prebiotics, helminths, monoclonal antibodies, and toll-like receptor agonists, are also summarized.

Food allergy
Desensitization
Food immunotherapy
Omalizumab
Tolerance


Becoming parents again: Challenges affecting grandparent primary caregivers raising their grandchildren.

Abstract:
Background
A growing number of Canadian children live in the care of their grandparents, called skip-generation families. Reasons for this include teen pregnancy, death of a parent, mental/physical illnesses, and addictions. These grandparents and grandchildren are at increased risk of physical and mental illness, yet have few resources available to them.

Objective
Our study aims to describe the lived experiences of skip-generation families to better identify their needs.

Methods
We conducted semistructured interviews of grandparent primary caregivers from ten households in our community to chronicle their experiences raising their grandchildren. Participants were recruited by paediatricians using convenience sampling. Interviews were recorded, transcribed, and coded using Atlas Ti software, and classified into themes by consensus.

Results
Five primary themes emerged from the interviews: (1) Changes in family dynamics, (2) Psychosocial impact on grandchild and grandparent, (3) Lack of resources for grandparent caregivers, (4) The challenges of parenting later in life, and (5) Resilience inspired by the love of family. Many participants (n=10) described feeling unsupported after assuming care of their grandchildren and identified a need for additional counselling services, financial support and respite care. All (n=11) highlighted that caring for their grandchildren changed their lives in positive ways.

Conclusion
When grandparents are prioritized as primary caregivers for their grandchildren, our study suggests they receive insufficient community resources to meet their emotional, respite and financial needs. Further research involving this population in Canada is required. Paediatricians can play an essential role in recognizing these vulnerable families and advocating for additional supports and services.

Martin|Ashley|A| Albrechtsons|Daniel|D| MacDonald|Noni|N| Aumeerally|Nadia|N| Wong|Tania|T|

Grandparents
Caregivers
Skip-generation families
Paediatrician
Canada


Evaluation of the impacts of climate change on disease vectors through ecological niche modelling.

Abstract: Vector-borne diseases are exceptionally sensitive to climate change. Predicting vector occurrence in specific regions is a challenge that disease control programs must meet in order to plan and execute control interventions and climate change adaptation measures. Recently, an increasing number of scientific articles have applied ecological niche modelling (ENM) to study medically important insects and ticks. With a myriad of available methods, it is challenging to interpret their results. Here we review the future projections of disease vectors produced by ENM, and assess their trends and limitations. Tropical regions are currently occupied by many vector species; but future projections indicate poleward expansions of suitable climates for their occurrence and, therefore, entomological surveillance must be continuously done in areas projected to become suitable. The most commonly applied methods were the maximum entropy algorithm, generalized linear models, the genetic algorithm for rule set prediction, and discriminant analysis. Lack of consideration of the full-known current distribution of the target species on models with future projections has led to questionable predictions. We conclude that there is no ideal 'gold standard' method to model vector distributions; researchers are encouraged to test different methods for the same data. Such practice is becoming common in the field of ENM, but still lags behind in studies of disease vectors.

Carvalho|B M|BM|
Rangel|E F|EF|
Vale|M M|MM|

vector-borne diseases
Aedes
Anopheles
Culicoides
Ixodes
Lutzomyia
Phlebotomus
Triatoma
ensemble modelling
spatial distribution


Investigation of the Maturity Evaluation Indicator of Honey in Natural Ripening Process: The Case of Rape Honey.

Abstract: Honey maturity, a critical factor for quality evaluation, is difficult to detect in the current industry research. The objective of this study was to explore the changes in the composition and find potential maturity indicators of rape honey at different maturity stages through evaluating physicochemical parameters (moisture, sugars, pH, electrical conductivity, total protein, total phenols, total flavonoids, proline, and enzyme activity), the antioxidant capacity, and volatile components. The relevant results are as follows: 1. As the maturity increased, the moisture, sucrose, and maltose content of rape honey gradually decreased, while the glucose, fructose, and total protein content gradually increased. The activities of diastase, invertase, and β-glucosidase showed a significant increase with the elevation of ripening days, and the activity of glucose oxidase reached the highest before completely capping. 2. The antioxidant capacity of honey increased with the increase in honey maturity. There is a significant and strong correlation between the bioactive components of rape honey and antioxidant capacity (p < 0.01, |r| > 0.857). 3. Thirty-five volatile components have been identified. Nonanal, benzaldehyde monomer, and benzaldehyde dimer can be used as potential indicators for the identification of honey maturity stages. Principal component analysis (PCA) based on antioxidant parameters and volatile components can identify the maturity of honey.

Zhang|Guo-Zhi|GZ|0000-0002-0420-871X Tian|Jing|J| Zhang|Yan-Zheng|YZ|0000-0001-8695-9164 Li|Shan-Shan|SS| Zheng|Huo-Qing|HQ| Hu|Fu-Liang|FL|

maturity
rape honey
antioxidant
volatile profile


Deep Convolutional Neural Network-Based Lymph Node Metastasis Prediction for Colon Cancer Using Histopathological Images.

Abstract:
Background
Human evaluation of pathological slides cannot accurately predict lymph node metastasis (LNM), although accurate prediction is essential to determine treatment and follow-up strategies for colon cancer. We aimed to develop accurate histopathological features for LNM in colon cancer.

Methods
We developed a deep convolutional neural network model to distinguish the cancer tissue component of colon cancer using data from the tissue bank of the National Center for Tumor Diseases and the pathology archive at the University Medical Center Mannheim, Germany. This model was applied to whole-slide pathological images of colon cancer patients from The Cancer Genome Atlas (TCGA). The predictive value of the peri-tumoral stroma (PTS) score for LNM was assessed.

Results
A total of 164 patients with stages I, II, and III colon cancer from TCGA were analyzed. The mean PTS score was 0.380 (± SD = 0.285), and significantly higher PTS scores were observed in patients in the LNM-positive group than those in the LNM-negative group (P < 0.001). In the univariate analyses, the PTS scores for the LNM-positive group were significantly higher than those for the LNM-negative group (P < 0.001). Further, the PTS scores in lymphatic invasion and any one of perineural, lymphatic, or venous invasion were significantly increased in the LNM-positive group (P < 0.001 and P < 0.001).

Conclusion
We established the PTS score, a simplified reproducible parameter, for predicting LNM in colon cancer using computer-based analysis that could be used to guide treatment decisions. These findings warrant further confirmation through large-scale prospective clinical trials.

Kwak|Min Seob|MS|
Lee|Hun Hee|HH|
Yang|Jae Min|JM|
Cha|Jae Myung|JM|
Jeon|Jung Won|JW|
Yoon|Jin Young|JY|
Kim|Ha Il|HI|

metastasis
colorectal cancer
deep learning–artificial neural network
histology
prognostic score


Ultrasound-Guided Fine-Needle Aspiration of Superficial Lymphadenopathy Performed by Interventional Pathologists: The Applicability of the Sydney System from 2 Years of Experience and 363 Cases.

Abstract:
INTRODUCTION
The Sydney system proposal for the study and reporting of lymphadenopathy by fine-needle aspiration (FNA) constitutes one of the first attempts to standardize this procedure. Here, we review its applicability.

MATERIALS AND METHODS
A retrospective study in which all ultrasound-guided FNAs (USFNAs) of superficial lymphadenopathy (palpable or not) performed by interventional pathologists in 2 specialized hospital centers were quantified over 2 years. The procedure was systematized, and the diagnoses were reclassified according to the Sydney system categories.

RESULTS
We analyzed 363 USFNAs of lymphadenopathies. The distribution of cases by categories was as follows: insufficient (n = 13; 3.58%), benign (n = 208; 57.30%), atypia of uncertain significance (n = 7; 1.93%), suspicious (n = 21; 5.79), and malignant (n = 114; 31.40%). The risks of malignancy calculated for categories I, II, III, IV, and V were 27%, 3%, 50%, 100%, and 100%, respectively.

CONCLUSION
The implementation of the Sydney system allows the systematization and standardization of the lymph node FNA methodology, with increased efficacy and efficiency. Assimilating the recommendations enables the qualification of the diagnostic procedure.

Torres Rivas|Héctor Enrique|HE|
Villar Zarra|Karen|K|
Pérez Pabón|Lisseth Andrea|LA|
González Gutierréz|María de la Paz|MP|
Zapico Ortiz|Nuria|N|
Olmo Fernández|María Del Mar|MDM|
Nieto Llanos|Santiago|S|
Antoranz Álvarez|Natividad|N|
Gómez Martín|Ángel|Á|
Fernández Fernández|Luis Manuel|LM|

Fine-needle aspiration
Interventional pathologist
The Sydney system
Lymph node cytology


The effects of eye coordination during deep cervical flexor training on the thickness of the cervical flexors.

Abstract: [Purpose] The purpose of this study was to identify changes in the thicknesses of the cervical flexors according to eye coordination during deep cervical flexor training. [Subjects and Methods] Twenty normal adults were randomly selected, and during their deep cervical flexor training and eye tracking, the thicknesses of the longus colli and the sternocleidomastoid were measured using ultrasonic waves. [Results] The thickness of the longus colli statistically significantly increased when deep cervical flexor training and eye coordination were performed simultaneously. However, the thickness of the sternocleidomastoid did not show statistically significant differences according to eye coordination. [Conclusion] Eye coordination during deep cervical flexor training is likely to increase the thickness of the longus colli selectively.

Moon|Hyun-Ju|HJ| Goo|Bong-Oh|BO| Kwon|Hae-Yeon|HY| Jang|Jun-Hyeok|JH|

Eye coordination
Deep cervical flexor training
Thickness of cervical flexors


Socio-demographic and clinical profile of substance abuse patients admitted to an emergency department in Ankara, Turkey.

Abstract:
BACKGROUND
Illicit drug abuse is an important health problem around the world. Cannabis is the most commonly used illicit drug, followed by amphetamines, opioids, and cocaine. In this study, we searched the socio-demographic features of drug abusers admitted to an emergency department.

MATERIALS AND METHODS
The study was performed in the emergency department of an education and training hospital in Ankara, Turkey. The socio-demographic features, substances commonly consumed, and the reason for the patients' presentation were recorded.

RESULTS
The mean age of patients was 28.3±9.2. Of those under study, 93.3% were male; 68.7% were discharged from the emergency department after a short observation period; and 10.4% were hospitalized. The median age of the patients' first experience with illicit substances was 19 (4-56).

CONCLUSION
Illicit drug use remains a significant medical health problem, not only in Turkey but also around the world. Abusers frequently seek emergency services, complaining of various symptoms, but generally do not mention their substance abuse. Emergency physicians must ask patients if they use abuse drugs.

Avci|Sema|S|
Sarikaya|Ridvan|R|
Kavak|Nezih|N|
Özmen|Fatma Nihal|FN|
Aydin|Macit|M|
Arslan|Engin Deniz|ED|
Büyükcam|Fatih|F|

substance abuse, illicit drug, emergency department, socio-demographic profile


The Usefulness of Spectroscopic Simulations.

Abstract: This article presents a method for extracting the optical constants of homogeneous isotropic materials using the infrared spectra of that material. The method is based on using the harmonic oscillator model of molecular polarizability to obtain optical constants, then calculating the spectrum, comparing the calculated spectrum to an experimental spectrum of the material, and adjusting the model parameters until a close fit between the spectra is obtained. Corrections that need to be made to the experimental spectra in order to remove instrumental distortions are also briefly described. The remainder of the article centers on describing how the optical constants can be used to simulate spectra of that material in different experimental arrangements and the benefits that spectral simulations afford to experimentalists.

optical constants
Spectral simulations
infrared spectrometry
vibrational spectra


Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?

Abstract: The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view ('pros' and 'cons'), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.

Salvarani|Carlo|C| Soriano|Alessandra|A| Muratore|Francesco|F| Shoenfeld|Yehuda|Y| Blockmans|Daniel|D|

D000072078:Positron Emission Tomography Computed Tomography

PET
CT
Imaging
Large vessel vasculitis
Fluorodeoxyglucose
Positron emission tomography
Computed tomography
Giant cell arteritis (GCA)
(18)F-FDG
Temporal artery


A new species of Lobesia Guenée, 1845 from Thailand (Lepidoptera: Tortricidae: Oletheutinae).

Abstract: Lobesia bisacca Charoensub and Pinkaew, n.sp., is described from Thailand. Specimens were collected in light traps in Trat Province, eastern Thailand and were deposited in the Kasetsart Kamphaengsaen Insect Collection. The new species can be distinguished from all other congeners by the unusual, long, protruding process from the base of the sacculus in the male genitalia. Illustrations of the adult, male genitalia, and male secondary characters are provided.

Lepidoptera, hairpencil, morphology, new species, Olethreutini, Tortricidae


Proximal tibial morphology and its correlation with osteochondritis dissecans of the knee.

Abstract:
PURPOSE
The relationship of proximal tibial morphology to the presence of femoral osteochondritis dissecans (OCD) lesions is unknown. This radiographic study tested the null hypothesis that knees with unilateral medial or lateral OCD lesions would have no difference in the slope of their medial, lateral, or posterior tibial plateau compared with unaffected knees.

METHODS
There were 72 patients with unilateral OCD lesions of the medial or lateral femoral condyle seen at our institution from 2005 to 2011. On AP and lateral radiographs of the knee, three examiners conducted independent measurements of the tibial plateau posterior slope, as well as medial and lateral slope as measured from the peak of the tibial spine to the edge of the plateau on the side of the corresponding OCD lesion. Measurements were repeated on normal contralateral and matched control knees.

RESULTS
Knees with medial femoral condyle OCD lesions had greater medial tibial slope compared with normal contralateral knees (p = 0.007) and normal controls (p < 0.04). Knees with lateral femoral condyle OCD lesions had no significant difference in lateral tibial slope compared with the contralateral knee or matched controls. Posterior slope was greater in knees with medial OCD lesions than matched controls (p = 0.007). Intraclass correlation coefficients demonstrated consistency between observers for all measurements.

CONCLUSION
An assessment of proximal tibial morphology demonstrated greater medial and posterior tibial slope in knees with medial OCD lesions compared with normal knees. The technique for measuring medial and lateral tibial slope was reliable among evaluators. The clinical relevance is that proximal tibial morphology may have a relationship with OCD lesions.

LEVEL OF EVIDENCE
III.

Wechter|John F|JF|
Sikka|Robby Singh|RS|
Alwan|Mujtaba|M|
Nelson|Bradley J|BJ|
Tompkins|Marc|M|

Osteochondritis dissecans
Knee
Tibial slope


Sulodexide for the Symptoms and Signs of Chronic Venous Disease: A Systematic Review and Meta-analysis.

Abstract:
INTRODUCTION
Chronic venous disease (CVD) is a common condition associated with valvular dysfunction, venous hypertension and endothelial inflammation. Sulodexide facilitates the healing of venous ulcers and is frequently used in patients with CVD without ulcer. This review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD.

METHODS
We searched MEDLINE, EMBASE, CINAHL and AMED as well as the Cochrane Central Register of Controlled Trials and the World Health Organisation (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings and journal supplements. Any study monitoring any effect of sulodexide in patients with CVD at any stage of the disease, classified or non-classified, was considered. Treatment effects were estimated using standardised mean differences (SMDs), mean differences (MDs) and risk ratios (RRs), as appropriate. We calculated 95% confidence intervals (CIs) and heterogeneity (Q, tau and I2).

RESULTS
The search found 64 studies, but only 23 provided data on 7153 participants (mean age 55 years; 68% female). The 13 studies providing extractable quantitative information included 1901 participants (mean age 55.2 years; 65% female). Sulodexide decreased the intensity of pain, cramps, heaviness, oedema and total symptom score and reduced inflammatory mediators in patients with CVD. The risk of adverse events (AEs) was not different between sulodexide and placebo or heparan sulphate (RR 1.31, 95% CI 0.74-2.32; I2 = 0%; 270 participants). The overall risk of AEs with sulodexide was low: 3% (95% CI 1-4%) estimated from 3656 participants.

CONCLUSION
Sulodexide was found to have a beneficial venoactive effect on the major signs and symptoms of CVD such as pain, cramps, heaviness and oedema without increasing the risk of AEs. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines.

Sulodexide
Chronic venous disease
Meta-analysis
Efficacy
Safety


Prevalence and Clinical Correlates of Extended Mechanical Support in Patients Undergoing High-Risk Percutaneous Coronary Intervention in Current Clinical Practice: Insights from the cVAD Registry.

Abstract:
BACKGROUND
High-risk percutaneous coronary interventions (HR-PCI) are prone to hemodynamic instability, resulting in poor outcomes. Acute mechanical circulatory support (AMCS) devices are used during HR-PCI to improve outcomes. However, the clinical criteria for extended AMCS have not been well characterized. The aim of this study was to describe the prevalence and clinical correlates of extended AMCS in patients undergoing elective or urgent HR-PCI.

METHODS
We retrospectively analyzed 507 patients enrolled in the catheter-based ventricular assist device (cVAD) registry who underwent elective or urgent HR-PCI with prophylactic use of Impella. The study population was divided into two groups: Impella support removed immediately after PCI (Group A, n = 464) and extended support after PCI (Group B, n = 43). Multivariable regression analysis was used to identify independent predictors of extended AMCS.

RESULTS
Baseline characteristics were similar between the groups. Non-ST-elevation myocardial infarction in 26.3% in Group A vs 41.8% in Group B (p = 0.03). PCI of left main was common in Group A (p = 0.02), whereas the right coronary artery was common in Group B (p < 0.001). The mean duration of Impella support 1.1 ± 0.6 h in Group A vs 11.4 ± 16.8 h in Group B (p < 0.001). Death and vascular complications were higher with extended Impella support. Revascularization of chronic total occlusion (CTO) was an independent predictor of extended Impella support (OR 3.2, 95% CI 1.20-8.53).

CONCLUSIONS
About 9% of patients enrolled in the cVAD registry undergoing elective or urgent HR-PCI received extended Impella support. In-hospital mortality was about 12% in patients requiring extended Impella support. CTO was associated with a higher likelihood of extended AMCS. The hemodynamic benefits of extended AMCS support must be weighed in terms of risk of complications.

Davila|Carlos D|CD|
Sharma|Saurabh|S|
Krishnamoorthy|Parasuram|P|
Rengifo-Moreno|Pablo|P|
Palacios|Igor F|IF|
O'Neill|William|W|
Kapur|Navin K|NK|
Witzke|Christian F|CF|

Acute mechanical circulatory support
Impella
Complex coronary interventions
Vascular access


Prognostic value of lymphovascular invasion in Bismuth-Corlette type IV hilar cholangiocarcinoma.

Abstract:
AIM
To assess the prognostic value of lymphovascular invasion (LVI) in Bismuth-Corlette type IV hilar cholangiocarcinoma (HC) patients.

METHODS
A retrospective analysis was performed on 142 consecutively recruited type IV HC patients undergoing radical resection with at least 5 years of follow-up. Survival analysis was performed by the Kaplan-Meier method, and the association between the clinicopathologic variables and survival was evaluated by log-rank test. Multivariate analysis was adopted to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Multiple logistic regression analysis was performed to determine the association between LVI and potential variables.

RESULTS
LVI was confirmed histopathologically in 29 (20.4%) patients. Multivariate analysis showed that positive resection margin (HR = 6.255, 95%CI: 3.485-11.229, P < 0.001), N1 stage (HR = 2.902, 95%CI: 1.132-7.439, P = 0.027), tumor size > 30 mm (HR = 1.942, 95%CI: 1.176-3.209, P = 0.010) and LVI positivity (HR = 2.799, 95%CI: 1.588-4.935, P < 0.001) were adverse prognostic factors for DFS. The independent risk factors for OS were positive resection margin (HR = 6.776, 95%CI: 3.988-11.479, P < 0.001), N1 stage (HR = 2.827, 95%CI: 1.243-6.429, P = 0.013), tumor size > 30 mm (HR = 1.739, 95%CI: 1.101-2.745, P = 0.018) and LVI positivity (HR = 2.908, 95%CI: 1.712-4.938, P < 0.001). LVI was associated with N1 stage and tumor size > 30 mm. Multiple logistic regression analysis indicated that N1 stage (HR = 3.312, 95%CI: 1.338-8.198, P = 0.026) and tumor size > 30 mm (HR = 3.258, 95%CI: 1.288-8.236, P = 0.013) were associated with LVI.

CONCLUSION
LVI is associated with N1 stage and tumor size > 30 mm and adversely influences DFS and OS in type IV HC patients.

Li|Bei|B| Xiong|Xian-Ze|XZ| Zhou|Yong|Y| Wu|Si-Jia|SJ| You|Zhen|Z| Lu|Jiong|J| Cheng|Nan-Sheng|NS|

Lymphovascular invasion
Hilar cholangiocarcinoma
Overall survival
Disease-free survival
Bismuth-Corlette classification


Comparison of ultrasound-enhanced air-assisted liquid-liquid microextraction and low-density solvent-based dispersive liquid-liquid microextraction methods for determination of nonsteroidal anti-inflammatory drugs in human urine samples.

Abstract: Two dispersive-based liquid-liquid microextraction methods including ultrasound-enhanced air-assisted liquid-liquid microextraction (USE-AALLME) and low-density solvent-based dispersive liquid-liquid microextraction (LDS-DLLME) were compared for the extraction of salicylic acid (the hydrolysis product of acetylsalicylic acid), diclofenac and ibuprofen, as instances of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), in human urine prior to their determination by gas chromatography with flame ionization detection (GC-FID). The influence of different parameters affecting the USE-AALLME (including type and volume of the extraction solvent, sample pH, ionic strength, and simultaneous sonication and number of extraction cycles) and the LDS-DLLME (including type and volume of the extraction and disperser solvents, sample pH, and ionic strength) were investigated to optimize their extraction efficiencies. Both methods are fast, simple and convenient with organic solvent consumption at μL level. However, the best results were obtained using the USE-AALLME method, applying 30 μL of 1-octanol as extraction solvent, 5.0 mL of sample at pH 3.0, without salt addition, and 5 extraction cycles during 20s of sonication. This method was validated based on linearities (r(2) >0 .971), limits of detection (0.1-1.0 μg L(-1)), linear dynamic ranges (0.4-1000.0 μg L(-1)), enrichment factors (115 ± 3-135 ± 3), consumptive indices (0.043-0.037), inter- and intra-day precisions (4.3-4.8 and 5.6-6.1, respectively), and relative recoveries (94-103%). The USE-AALLME in combination with GC-FID, and with no need to derivatization step, was demonstrated to be a simple, inexpensive, sensitive and efficient method to determine NSAIDs in human urine samples.

Barfi|Behruz|B|
Asghari|Alireza|A|
Rajabi|Maryam|M|
Goochani Moghadam|Ahmad|A|
Mirkhani|Nasim|N|
Ahmadi|Farhad|F|


Infection-provoked psoriasis: Induced or aggravated (Review).

Abstract: Psoriasis is a common chronic, immune-mediated, inflammatory skin disorder, with a reported prevalence of 0.0-2.1% among children and 0.91-8.50% among adults, worldwide. Psoriasis is induced by several environmental factors, including infection, alcohol consumption, drugs, trauma, acute withdrawal of systemic or potent topical corticosteroids, body mass index and endocrine disorders. Increasing evidence suggest that a variety of microorganisms play key roles in the induction and exacerbation of psoriasis. Pathogens, such as streptococci and staphylococci are considered causal factors, presumably via superantigen activation of skin-seeking T cells. In addition, fungal pathogens, such as Candida and Malassezia, and viral agents, such as human immunodeficiency virus, hepatitis C virus infection and human papillomavirus, are also closely associated with psoriasis. Recently, several types of pathogens, such as Helicobacter pylori infection, Zika virus and scabies, have been reported to potentially trigger psoriasis. The present review discusses the underlying molecular mechanisms by which these infections influence psoriasis to provide a better understanding of the pathogenesis of psoriasis.

Teng|Yan|Y| Xie|Wenqing|W| Tao|Xiaohua|X| Liu|Na|N| Yu|Yong|Y| Huang|Youming|Y| Xu|Danfeng|D| Fan|Yibin|Y|

psoriasis microorganisms bacteria fungi viruses


Commentary on Bowe et al, "The State of the Otolaryngology Match: A Review of Applicant Trends, 'Impossible' Qualifications, and Implications".

Abstract: An objective evidence-based review of the metrics used to evaluate applicants entering our field ultimately found these figures to have upward trends without any major correlation to performance in residency. The rise of these metrics coincides with a yearly drop in senior applicants, and in 2017, nearly 10% of programs did not match their contingent. The causes of unmatched spots must be examined to ensure that the field of otolaryngology can continue to grow and attract medical students who will excel in our field. Considerations into revising the applicant selection process, early introduction and mentorship within the otolaryngology field, and changes to the current otolaryngology interview process are discussed.

Bhalla|Vidur|V|
Sykes|Kevin J|KJ|
Kraft|Shannon M|SM|
Chiu|Alexander G|AG|

D007396:Internship and Residency
D010036:Otolaryngology
D010560:Personnel Selection
D013337:Students, Medical
D014481:United States

otolaryngology
applicants
metrics
residency
medical student
selection
interview


Impaired intestinal barrier function in type 2 diabetic patients measured by serum LPS, Zonulin, and IFABP.

Abstract:
INTRODUCTION
The epithelial tight junctions of intestine were impaired in murine model of type 2 diabetes mellitus (T2DM). The aim of this work was to investigate the alteration of intestinal barrier in T2DM patients.

METHODS
90 patients with T2DM and 28 healthy controls were recruited. Serum lipopolysaccharide (LPS), Zonulin, and intestinal fatty acid binding protein (IFABP) were measured by ELISA, based on which a derived permeability risk score (PRS) was calculated. Subgroup analyses were conducted based on the glycemic control (HbA1c < 7%, or HbA1c ≥ 7%), the amount of chronic diabetic complications, and the use of aspirin at the time.

RESULTS
Serum LPS, Zonulin, and IFABP, and PRS of T2DM group were significantly higher than those of the control group (p < 0.05 for all). Serum LPS and PRS was higher in T2DM patients with poor glycemic control (both p < 0.05). Patients with more chronic complications of diabetes had higher serum LPS and IFABP, and PRS (all p < 0.05). No differences were found in these serum markers between T2DM patients being treated with aspirin or not.

CONCLUSIONS
Intestinal barrier function was impaired in T2DM patients. Poor glycemic control and more chronic complications of diabetes were associated with worse intestinal barrier function. Treatment with aspirin did not aggravate the impairment of intestinal barrier in T2DM patients.

Yuan|Jie-Hao|JH| Xie|Qing-Sheng|QS| Chen|Guang-Cheng|GC| Huang|Chu-Lin|CL| Yu|Tao|T| Chen|Qi-Kui|QK| Li|Jie-Yao|JY|

Intestinal barrier function
LPS
Zonulin
IFABP
Type 2 diabetes mellitus


Resource efficiency and culture--workplace training for small and medium-sized enterprises.

Abstract: Although there are already some qualification offers available for enterprises to support resource efficiency innovations, the high potentials that can be identified especially for small and medium sized enterprises (SMEs) have not been activated until now. As successful change lies in the hands of humans, the main aim of vocational education has to be the promotion of organisational and cultural changes in the enterprises. As there is already a small but increasing number of enterprises that perform very well in resource efficiency innovations one question arises: What are typical characteristics of those enterprises? Leaning on a good-practice approach, the project "ResourceCulture" is going to prove or falsify the hypothesis that enterprises being successful with resource efficiency innovations have a specific culture of trust, which substantially contributes to innovation processes, or even initially enables them. Detailed empirical field research will light up which correlations between resource efficiency, innovation and cultures of trust can be found and will offer important aspects for the improvement of management instruments and qualification concepts for workplace training. The project seizes qualification needs that were likewise mentioned by enterprises and consultants, regarding the implementation of resource efficiency. This article - based on first empirical field research results - derives preliminary indications for the design of the qualification module for the target groups resource efficiency consultants and managers. On this basis and in order to implement "ResourceCulture" conceptual and methodological starting points for workplace training are outlined.

D003247:Conservation of Natural Resources

Resource efficiency
Qualification
SMEs
Trust culture


3D CFD simulations of trailing suction hopper dredger plume mixing: comparison with field measurements.

Abstract: A 3D computational fluid dynamics (CFD) model is used to simulate mixing of an overflow plume within 400 m from a trailing suction hopper dredger (TSHD). The simulations are compared with new field measurements. It is the first time simulations of overflow dredging plumes are compared in such detail to field measurements this close to a TSHD. Seven cases with a large variety in overflow flux and plume characteristics are used. Measured maximum suspended sediment concentrations (SSC) vary between 30 and 500 mg/l and fluxes vary between 0.7% and 20% of the total overflow flux; the CFD model has, subject to the limitations of the field data, been shown to reproduce this in a satisfactory way. The model gives better understanding of important near field processes, which helps to assess the frequency, duration and intensity of stresses like turbidity and sedimentation needed to find the environmental impact of dredging projects.

de Wit|Lynyrd|L|
Talmon|A M|AM|
van Rhee|C|C|

Field measurements
Dredging
Sediment
Turbidity
Environmental impact
Turbulent plume mixing


Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: systematic review and meta-analysis of observational studies.

Abstract:
OBJECTIVE
To systematically analyze literature with the aim of examining whether rheumatoid factor (RF) is a predictor of response to tumor necrosis factor (TNF) antagonists in rheumatoid arthritis (RA).

METHODS
A systematic review and meta-analysis of observational studies were conducted. All studies on the association of baseline RF (titer and/or status) and response to any TNF antagonists, or with enough information to estimate this association were included. Qualitative analysis and meta-analysis using random-effects approach by type of outcome response and RF test was performed. Risk of publication bias was also evaluated.

RESULTS
The systematic review included 18 studies of 4163 identified articles, involving 5703 patients with homogeneous baseline characteristics. The most common outcome to assess response was European League Against Rheumatism (EULAR) response criteria, normally merging good and moderate categories as response. The weighted mean difference (WMD) of baseline IgM RF titer in meta-analysis was higher in the non-responders group [-101.58 (95% CI -156.58,-46.59) I2=0.0]. Combined odds ratios (ORs) of positive IgM RF, positive IgA RF, and positive IgG RF to achieve good/moderate response were 1.08 (0.80, 1.47), I2=40.9%; 0.83 (0.39, 1.73), I2=39.8%, and 1.30 (0.48, 3.51), I2=62.9%, respectively. We did not find an association between a positive IgM RF and EULAR good response or remission.

CONCLUSIONS
This meta-analysis does not support baseline IgM RF titer as a predictor of response to TNF antagonists in RA. However, this conclusion is hampered by high heterogeneity in the studies included in this meta-analysis.

Salgado|Eva|E|
Maneiro|José Ramón|JR|
Carmona|Loreto|L|
Gómez-Reino|Juan|J|

Rheumatoid factor
TNF antagonists
Rheumatoid arthritis


High-risk human papillomavirus targets crossroads in immune signaling.

Abstract: Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.

Tummers|Bart|B|
Burg|Sjoerd H Van Der|SH|

high-risk human papillomavirus
keratinocyte
immune evasion


Taste receptors in the upper airway.

Abstract: Taste receptors were named for their originally-identified expression on the tongue and role in the sensation of taste (gustation). They are now known to be involved in many chemosensory processes outside the tongue. Expression of the receptors for bitter, sweet, and umami was recently identified in many organs, including the brain, airway, gastrointestinal tract, and reproductive systems. We do not yet know the full roles of these receptors in all of these tissues, nor do we know all of the endogenous ligands that activate them. However, taste receptors are emerging as potentially important therapeutic targets. Moreover, they may mediate some off target effects of drugs, as many medications in common clinical use are known to be bitter. The focus of this review is on recent basic and clinical data describing the expression of bitter (T2R) and sweet (T1R) receptors in the airway and their activation by secreted bacterial compounds. These receptors play important roles in innate immune nitric oxide production and antimicrobial peptide secretion, and may be useful targets for stimulating immune responses in the upper respiratory tract via topical therapies. Moreover, genetic variation in these receptors may play a role in the differential susceptibility of patients to certain types of respiratory infections as well as to differential outcomes in patients with chronic rhinosinusitis (CRS). CRS is a syndrome of chronic upper respiratory infection and inflammation and has a significant detrimental impact on patient quality of life. CRS treatment accounts for approximately 20% of adult antibiotic prescriptions and is thus a large driver of the public health crisis of antibiotic resistance. Taste receptors represent a novel class of therapeutic target to potentially stimulate endogenous immune responses and treat CRS patients without conventional antibiotics.

Gustation
Innate immunity
Nitric oxide
Antimicrobial peptide
Respiratory infection
Chronic rhinosinusitis
Cilia
Nasal disease


Could ventriculoperitoneal shunt and tracheotomy procedures be realized in the same surgical time?

Abstract:
BACKGROUND
Both tracheotomy and ventriculoperitoneal shunting procedures may be required for the same critically ill patient. However, the risk of surgical site infection (SSI) may be increased if both procedures are performed simultaneously.

METHOD
We performed a retrospective analysis of 41 consecutive patients who underwent both procedures simultaneously in our institution between March 2000 and January 2008.

RESULTS
Analysis revealed no difference in SSI rate between patients undergoing both procedures simultaneously and in staged procedures.

CONCLUSIONS
VP shunting and tracheotomy procedures could be performed simultaneously without increasing the risk of surgical site infection. Such strategy may shorten the length of stay in critical care units.

Seizeur|R|R| Magro|E|E| Allano|V|V| Abed-Rabbo|F|F| Obaid|S|S| Reynaud|P|P|

Surgical site infection
Hemorrhage
Hydrocephalus
Tracheostomy
VP-shunt


Factors associated with actual skeletal muscle mass increase during hip fracture rehabilitation of persons aged 80 and older.

Abstract:
OBJECTIVES
This study aimed to evaluate actual skeletal muscle mass change and factors associated with its increase in patients aged ≥80 years undergoing hip fracture rehabilitation.

METHODS
This case-control study was conducted in the rehabilitation hospital. Participants were 368 patients aged ≥80 years undergoing hip fracture rehabilitation. Patients were divided into two groups based on the change of skeletal muscle mass index (SMI) during hospitalization: two groups with increased SMI and without increased SMI, after evaluation of skeletal muscle mass changes. Analysis between two groups and multivariate logistic regression analysis were performed to evaluate the factors associated with SMI increases.

RESULTS
The SMI at discharge was significantly increased (5.20 kg/m2) compared to baseline (5.00 kg/m2; p <0.001). The significant differences were observed in SMI on admission, length of hospital stay, duration of exercise therapy and BMI gain between two groups. Multiple logistic regression analysis showed that hospital stay and period of exercise therapy were significantly associated with increased SMI (OR: 1.020, and 1.010 respectively; and 95% CIs: 1.010-1.030, and 1.000-1.030, respectively). Moreover, BMI and SMI on admission, and BMI gain were significantly associated with increased SMI.

CONCLUSIONS
We demonstrated that old patients with hip fractures achieved significantly increased skeletal muscle mass during rehabilitation and that BMI and SMI on admission, BMI gain, length of hospital stay, and duration of exercise therapy were factors independently associated with increased SMI. Even older patients should take exercise to acquire skeletal muscle, rather than refraining from exercising due to old age or hip fractures.

Ogawa|Takahiro|T| Sato|Keisuke|K| Nakayama|Yuki|Y| Nakazato|Akie|A| Zaha|Masanari|M| Isa|Ayano|A| Kugai|Hirofumi|H| Nakahama|Masumi|M|

Aged
Frail elderly
Length of stay
Protein
Sarcopenia


Does life satisfaction predict five-year mortality in community-living older adults?

Abstract:
OBJECTIVES
Depression and depressive symptoms predict death, but it is less clear if more general measures of life satisfaction (LS) predict death. Our objectives were to determine: (1) if LS predicts mortality over a five-year period in community-living older adults; and (2) which aspects of LS predict death.

METHOD
1751 adults over the age of 65 who were living in the community were sampled from a representative population sampling frame in 1991/1992 and followed five years later. Age, gender, and education were self-reported. An index of multimorbidity and the Older American Resource Survey measured health and functional status, and the Terrible-Delightful Scale assessed overall LS as well as satisfaction with: health, finances, family, friends, housing, recreation, self-esteem, religion, and transportation. Cox proportional hazards models examined the influence of LS on time to death.

RESULTS
417 participants died during the five-year study period. Overall LS and all aspects of LS except finances, religion, and self-esteem predicted death in unadjusted analyses. In fully adjusted analyses, LS with health, housing, and recreation predicted death. Other aspects of LS did not predict death after accounting for functional status and multimorbidity.

CONCLUSION
LS predicted death, but certain aspects of LS are more strongly associated with death. The effect of LS is complex and may be mediated or confounded by health and functional status. It is important to consider different domains of LS when considering the impact of this important emotional indicator on mortality among older adults.

St John|Philip D|PD|
Mackenzie|Corey|C|
Menec|Verena|V|

life satisfaction
mortality
Terrible–Delightful Scale
subjective well-being


Mesenchymal-Epithelial Transition in Fibroblasts of Human Normal Lungs and Interstitial Lung Diseases.

Abstract: . In passages above ten and growing very actively, we observed that some human lung fibroblasts cultured under standard conditions were transformed into a lineage of epithelial-like cells (ELC). To systematically evaluate the possible mesenchymal-epithelial transition (MET) occurrence, fibroblasts were obtained from normal lungs and also from lungs affected by idiopathic interstitial diseases. When an unusual epithelial-like phenotypic change was observed, cultured cells were characterized by confocal immunofluorescence microscopy, immunoblotting, immunocytochemistry, cytofluorometry, gelatin zymography, RT-qPCR, and hybridization in a whole-transcript human microarray. Additionally, microvesicles fraction (MVs) from ELC and fibroblasts were used to induce MET, while the microRNAs (miRNAs) contained in the MVs were identified. Pattern-gene expression of the original fibroblasts and the derived ELC revealed profound changes, upregulating characteristic epithelial-cell genes and downregulating mesenchymal genes, with a marked increase of E-cadherin, cytokeratin, and ZO-1, and the loss of expression of α-SMA, collagen type I, and Thy-1 cell surface antigen (CD90). Fibroblasts, exposed to culture media or MVs from the ELC, acquired ELC phenotype. The miRNAs in MVs shown six expressed exclusively in fibroblasts, and three only in ELC; moreover, twelve miRNAs were differentially expressed between fibroblasts and ELC, all of them but one was overexpressed in fibroblasts. These findings suggest that the MET-like process can occur in human lung fibroblasts, either from normal or diseased lungs. However, the biological implication is unclear.

fibroblast
epithelial-like cell
microRNA
E-cadherin
collagen type I
mesenchymal–epithelial transition
α-smooth muscle actin


Update: use of the benchmark dose approach in risk assessment.

Abstract: The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the NOAEL approach for deriving a Reference Point (RP). Most of the modifications made to the SC guidance of 2009 concern the section providing guidance on how to apply the BMD approach. Model averaging is recommended as the preferred method for calculating the BMD confidence interval, while acknowledging that the respective tools are still under development and may not be easily accessible to all. Therefore, selecting or rejecting models is still considered as a suboptimal alternative. The set of default models to be used for BMD analysis has been reviewed, and the Akaike information criterion (AIC) has been introduced instead of the log-likelihood to characterise the goodness of fit of different mathematical models to a dose-response data set. A flowchart has also been inserted in this update to guide the reader step-by-step when performing a BMD analysis, as well as a chapter on the distributional part of dose-response models and a template for reporting a BMD analysis in a complete and transparent manner. Finally, it is recommended to always report the BMD confidence interval rather than the value of the BMD. The lower bound (BMDL) is needed as a potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL per ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re-evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 SC guidance was used, in particular when the exposure is clearly smaller (e.g. more than one order of magnitude) than the health-based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the expected wide application of the BMD approach.

|||
Hardy|Anthony|A|
Benford|Diane|D|
Halldorsson|Thorhallur|T|
Jeger|Michael John|MJ|
Knutsen|Katrine Helle|KH|
More|Simon|S|
Mortensen|Alicja|A|
Naegeli|Hanspeter|H|
Noteborn|Hubert|H|
Ockleford|Colin|C|
Ricci|Antonia|A|
Rychen|Guido|G|
Silano|Vittorio|V|
Solecki|Roland|R|
Turck|Dominique|D|
Aerts|Marc|M|
Bodin|Laurent|L|
Davis|Allen|A|
Edler|Lutz|L|
Gundert-Remy|Ursula|U|
Sand|Salomon|S|
Slob|Wout|W|
Bottex|Bernard|B|
Abrahantes|Jose Cortiñas|JC|
Marques|Daniele Court|DC|
Kass|George|G|
Schlatter|Josef R|JR|

benchmark dose
BMD
NOAEL
BMDL
BMD software
benchmark response
dose–response modelling


Multiple System Atrophy Showing Portomesenteric Venous Gas with Pneumatosis Intestinalis on Abdominal Computed Tomography Associated with a Cause of Death.

Abstract: This manuscript describes the first known case of a patient with multiple system atrophy whose parasympathetic dominant disturbance might have been associated with the relative constriction of the superior mesenteric artery, leading to nonocclusive mesenteric ischemia and subsequent portomesenteric venous gas with pneumatosis intestinalis on abdominal computed tomography approaching death.

multiple system atrophy
portomesenteric venous gas
pneumatosis intestinalis


Effect of shaddock albedo addition on the properties of frankfurters.

Abstract: To explore the potential as a natural auxiliary emulsifier, shaddock albedo was added into frankfurters at six different levels: 0.0, 2.5, 5.0, 7.5, 10 and 12.5 %. The emulsion capacity (EC) of meat batters and cooking properties of frankfurters were evaluated. EC of meat batters was improved with the addition of shaddock albedo and the maximum value was reached at the 5 % albedo concentration. The addition of shaddock albedo resulted in lower cooking losses of frankfurters, with the lowest value obtained at the 7.5 % level. The presence of shaddock albedo decreased the total expressible fluid (TEF) and the proportion of fat in total expressible fluid (PF) which indicated the emulsion stability of frankfurters and the lowest values both occurred at the concentration of 7.5 %. Shaddock albedo inclusion increased the lightness and yellowness of frankfurters and decreased redness. Texture profile analysis showed increased hardness and decreased chewiness of frankfurters with the addition of shaddock albedo. Consequently, shaddock albedo could be a potential source of auxiliary emulsifier filler for emulsion-type meat products.

Shan|Bing|B| Li|Xingmin|X| Pan|Teng|T| Zheng|Limin|L| Zhang|Hao|H| Guo|Huiyuan|H| Jiang|Lu|L| Zhen|Shaobo|S| Ren|Fazheng|F|

Shaddock albedo
Frankfurters
Emulsion capacity
Cooking loss


Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease.

Abstract: Animal models of human disease provide an in vivo system that can reveal molecular mechanisms by which mutations cause pathology, and, moreover, have the potential to provide a valuable tool for drug development. Here, we have developed a zebrafish model of Parkinson's disease (PD) together with a novel method to screen for movement disorders in adult fish, pioneering a more efficient drug-testing route. Mutation of the PARK7 gene (which encodes DJ-1) is known to cause monogenic autosomal recessive PD in humans, and, using CRISPR/Cas9 gene editing, we generated a Dj-1 loss-of-function zebrafish with molecular hallmarks of PD. To establish whether there is a human-relevant parkinsonian phenotype in our model, we adapted proven tools used to diagnose PD in clinics and developed a novel and unbiased computational method to classify movement disorders in adult zebrafish. Using high-resolution video capture and machine learning, we extracted novel features of movement from continuous data streams and used an evolutionary algorithm to classify parkinsonian fish. This method will be widely applicable for assessing zebrafish models of human motor diseases and provide a valuable asset for the therapeutics pipeline. In addition, interrogation of RNA-seq data indicate metabolic reprogramming of brains in the absence of Dj-1, adding to growing evidence that disruption of bioenergetics is a key feature of neurodegeneration.This article has an associated First Person interview with the first author of the paper.

Parkinson's disease
PARK7
DJ-1
Video capture
Artificial intelligence
Gene targeting


Parcellation of the Hippocampus According to Its Connection Probability with Prefrontal Cortex Subdivisions in a Malaysian Malay Population: Preliminary Findings.

Abstract:
Background
Lesion studies have shown distinct roles for the hippocampus, with the dorsal subregion being involved in processing of spatial information and memory, and the ventral aspect coding for emotion and motivational behaviour. However, its structural connectivity with the subdivisions of the prefrontal cortex (PFC), the executive area of the brain that also has various distinct functions, has not been fully explored, especially in the Malaysian population.

Methods
We performed diffusion magnetic resonance imaging with probabilistic tractography on four Malay males to parcellate the hippocampus according to its relative connection probability to the six subdivisions of the PFC.

Results
Our findings revealed that each hippocampus showed putative connectivity to all the subdivisions of PFC, with the highest connectivity to the orbitofrontal cortex (OFC). Parcellation of the hippocampus according to its connection probability to the six PFC subdivisions showed variability in the pattern of the connection distribution and no clear distinction between the hippocampal subregions.

Conclusion
Hippocampus displayed highest connectivity to the OFC as compared to other PFC subdivisions. We did not find a unifying pattern of distribution based on the connectivity-based parcellation of the hippocampus.

Abdullah|Aimi Nadhiah|AN|
Ahmad|Asma Hayati|AH|
Zakaria|Rahimah|R|
Tamam|Sofina|S|
Abdullah|Jafri Malin|JM|

hippocampus
prefrontal cortex
diffusion magnetic resonance imaging


Tissue Engineering in Pediatric Bladder Reconstruction-The Road to Success.

Abstract: Several congenital disorders can cause end stage bladder disease and possibly renal damage in children. The current gold standard therapy is enterocystoplasty, a bladder augmentation using an intestinal segment. However, the use of bowel tissue is associated with numerous complications such as metabolic disturbance, stone formation, urine leakage, chronic infections, and malignancy. Urinary diversions using engineered bladder tissue would obviate the need for bowel for bladder reconstruction. Despite impressive progress in the field of bladder tissue engineering over the past decades, the successful transfer of the approach into clinical routine still represents a major challenge. In this review, we discuss major achievements and challenges in bladder tissue regeneration with a focus on different strategies to overcome the obstacles and to meet the need for living functional tissue replacements with a good growth potential and a long life span matching the pediatric population.

Horst|Maya|M| Eberli|Daniel|D| Gobet|Rita|R| Salemi|Souzan|S|

tissue engineering
pediatric
bladder augmentation
myelomeningocele
neurogenic bladder
stem cells


Modification of the Cavity of Plastic Injection Molds: A Brief Review of Materials and Influence on the Cooling Rates.

Abstract: In the 21st century, a great percentage of the plastic industry production is associated with both injection molding and extrusion processes. Manufactured plastic components/parts are used in several industry sectors, where the automotive and aeronautic stand out. In the injection process cycle, the cooling step represents 60% to 80% of the total injection process time, and it is used to estimate the production capabilities and costs. Therefore, efforts have been focused on obtaining more efficient cooling systems, seeking the best relationship between the shape, the quantity, and the distribution of the cooling channels into the injection molds. Concomitantly, the surface coating of the mold cavity also assumes great importance as it can provide increased hardness and a more straightforward demolding process. These aspects contribute to the decrease of rejected parts due to surface defects. However, the effect of the coated cavity on the heat transfer and, consequently, on the time of the injection cycle is not often addressed. This paper reviews the effects of the materials and surface coatings of molds cavity on the filling and cooling of the injection molding cycle. It shows how the design of cooling channels affects the cooling rates and warpage for molded parts. It also addresses how the surface coating influence the mold filling patterns and mold cooling. This review shows, more specifically, the influence of the coating process on the cooling step of the injection cycle and, consequently, in the productivity of the process.

Carrupt|Maria C|MC|
Piedade|Ana P|AP|0000-0002-1588-0640

cooling rate
molding cavity
injection molding of plastics
metallic and ceramic coatings


Laparoendoscopic single-site pyelolithotomy with use of a carter-thomason needle grasper.

Abstract:
PURPOSE
To study the feasibility and safety of the procedure, we present our early experience with laparoendoscopic single-site (LESS) pyelolithotomy performed by use of a Carter-Thomason needle grasper.

MATERIALS AND METHODS
Four patients underwent LESS pyelolithotomy for the removal of renal pelvic stones. The patients' mean age was 57.8 years, and their mean body mass index was 23.01. We used a homemade single-port device made with a surgical glove that was inserted into a 2.5-cm periumbilical incision. The operation was performed transperitoneally by using a Carter-Thomason grasper. After removal of the stone, a double-J stent was placed in situ, and laparoscopic intracorporeal suturing was performed. No additional ports were used.

RESULTS
All surgeries were completed successfully without conversion to conventional laparoscopy or open surgery. The mean operative time was 124.5 minutes, and the mean estimated blood loss was 255.2 mL. There were no significant complications, except in one patient who required a blood transfusion. The mean duration of hospital stay was 8.3 days. The mean stone size was 3.9 cm. Chemical analysis of the stones showed that three patients had calcium-containing stones and one patient had a uric acid stone. Postoperative radiologic study showed a stone clearance rate of 100%.

CONCLUSIONS
Our results, albeit limited, showed that LESS pyelolithotomy is a feasible and safe procedure. Especially with the use of a Carter-Thomason needle grasper, this operation can be performed without an additional port.

Laparoscopy
Surgical instruments
Urinary calculi


Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acid.

Abstract: Rho proteins are signalling molecules that control cellular dynamics, movement and morphological changes. They are activated by Rho guanine-nucleotide exchange factors (Rho GEFs) that transduce upstream signals into Rho-mediated activation of downstream processes. Fgd5 is a Rho GEF involved in angiogenesis and its target Rho protein for this process has been linked to Cdc42 activation. Here, we examined the function of purified Fgd5, specifically, which Rho proteins it activates and pinpoint the structural domains required for enzymatic activity. Using a GEF enzyme assay, we found that purified Fgd5 showed preferential activation of Rac1 and direct binding of Rac1 in pull-down and co-immunoprecipitation assays. Structural comparisons showed that the Fgd5 DH domain is highly similar to the Rac1 GEF, TrioN, supporting a role for Fgd5 as a Rac1 GEF. Compounds that bind to purified Fgd5 DH-PH protein were identified by screening a small molecule library via surface plasmon resonance. The effects of eleven ligands were further examined for their ability to inhibit the Fgd5 GEF enzymatic activity and Rac1 interaction. From these studies, we found that the compound aurintricarboxylic acid, and to a lesser extent mitoxantrone dihydrochloride, inhibited both Fgd5 GEF activation of Rac1 and their interaction. Aurintricarboxylic acid had no effect on the activity or binding of the Rac1 GEF, TrioN, thus demonstrating the feasibility of selectively disrupting Rho GEF activators. Abbreviations: a.a.: amino acid; ATA: aurintricarboxylic acid; DH: Dbl homology; DOCK: dictator of cytokinesis; Fgd: faciogenital dysplasia; GEF: guanine-nucleotide exchange factor; GST: glutathione S-transferase; LOPAC: library of pharmacologically active compounds; PH: pleckstrin homology; PDB: protein data bank; s.e.m.: standard error of the mean; SPR: surface plasmon resonance.

Park|Sally|S|
Guo|Yitian|Y|
Negre|Judeah|J|
Preto|Jordane|J|0000-0002-6041-4008
Smithers|Cameron C|CC|
Azad|Abul Kalam|AK|
Overduin|Michael|M|
Murray|Allan G|AG|
Eitzen|Gary|G|

aurintricarboxylic acid
guanine-nucleotide exchange factor
Rac1
surface plasmon resonance
Rho GTPase


Preparation of Lead-free Two-Dimensional-Layered (C8H17NH3)2SnBr4 Perovskite Scintillators and Their Application in X-ray Imaging.

Abstract: Scintillators, as spectral and energy transformers, are essential for X-ray imaging applications. However, their current disadvantages, including high-temperature sintering and generation of agglomerated powders or large bulk crystals, may not meet the increasing demands of low cost, nontoxicity, and flexible radiation detection. Thus, improved perovskite scintillators are developed in this research. A hybrid perovskite ((C8H17NH3)2SnBr4), which is nontoxic, lead-free, and organic-inorganic, is developed as a scintillator with good emission performance and radioluminescence intensity. These perovskite scintillators are synthesized at low temperatures in an aqueous acid solution, through which they generate a near-unity photoluminescence quantum yield of 98% with the excitation of ultraviolet light. As far as we know, this work is the first to show that the two-dimensional (2D) (C8H17NH3)2SnBr4 perovskite scintillator films prepared by coating a polymer layer can be applied to an X-ray imaging system. The results demonstrate that the low cost X-ray imaging device with good resolution and performance benefits dramatically from this lead-free organic-inorganic hybrid perovskite film. Therefore, this 2D-layered (C8H17NH3)2SnBr4 perovskite scintillator may be a high potential candidate for scintillating material for X-ray imaging techniques.

lead-free
perovskite scintillators
X-ray imaging
radioluminescence
composite films


Pain relieve without impairing muscle function after local infiltration anaesthesia in primary knee arthroplasty: a prospective randomized study.

Abstract:
PURPOSE
Purpose of the current study was to compare early effectiveness of pain relieve of 3 in 1 regional pain catheter to local infiltration anesthesia (LIA) in primary total knee arthroplasty (TKA). Secondary endpoint was quadriceps muscle strength after both procedures.

MATERIAL AND METHODS
A single-center, prospective, randomized controlled trial was performed. Patients eligible to TKA were either randomized into group 3 in 1 regional pain catheter (C), or group local infiltration anesthesia (L). Pain relieve was assessed by visual analogue scale (VAS) at rest and under physical activity (PA) prior to surgery (t0) and at days one through six. In addition, quadriceps muscle strength ( = straight leg raise) was tested according to the Manual Muscle Testing Scale. Functional outcome was measured using the Oxford Knee Score (OKS) preoperatively and 6 months postoperatively.

RESULTS
121 patients were included in the study. 59 (48.8%) patients were allocated to group C, 62 (51.2%) patients to Group L. No differences concerning pain level evaluated by VAS could be detected between the groups at any time. Comparing straight leg raise test group L was significantly superior over the complete postoperative period (p < 0.03). The mean OKS decreased significantly (p < 0.001) from preoperatively 34.2 ± 7.5 points to 16.9 ± 6.0 points at the six months final follow-up. Regarding OKS there were no intergroup differences at the final follow-up at 6 months postoperative.

CONCLUSION
There is no significant difference in pain relieve comparing LIA to 3 in 1 catheter in perioperative pain management in TKA. The advantage of LIA is unimpaired quadriceps muscle function in the short-term follow-up.

D000368:Aged
D000772:Anesthesia, Local
D019645:Arthroplasty, Replacement, Knee
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D059408:Pain Management
D010147:Pain Measurement
D010149:Pain, Postoperative
D020127:Recovery of Function
D016896:Treatment Outcome

Local infiltration anesthesia
TKA
Oxford knee score
3 in 1 catheter
Pain management
Quadriceps muscle function


Combining high-resolution gross domestic product data with home and personal care product market research data to generate a subnational emission inventory for Asia.

Abstract: Environmental risk assessment of chemicals is reliant on good estimates of product usage information and robust exposure models. Over the past 20 to 30 years, much progress has been made with the development of exposure models that simulate the transport and distribution of chemicals in the environment. However, little progress has been made in our ability to estimate chemical emissions of home and personal care (HPC) products. In this project, we have developed an approach to estimate subnational emission inventory of chemical ingredients used in HPC products for 12 Asian countries including Bangladesh, Cambodia, China, India, Indonesia, Laos, Malaysia, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam (Asia-12). To develop this inventory, we have coupled a 1 km grid of per capita gross domestic product (GDP) estimates with market research data of HPC product sales. We explore the necessity of accounting for a population's ability to purchase HPC products in determining their subnational distribution in regions where wealth is not uniform. The implications of using high resolution data on inter- and intracountry subnational emission estimates for a range of hypothetical and actual HPC product types were explored. It was demonstrated that for low value products (<500 US$ per capita/annum required to purchase product) the maximum deviation from baseline (emission distributed via population) is less than a factor of 3 and it would not result in significant differences in chemical risk assessments. However, for other product types (>500 US$ per capita/annum required to purchase product) the implications on emissions being assigned to subnational regions can vary by several orders of magnitude. The implications of this on conducting national or regional level risk assessments may be significant. Further work is needed to explore the implications of this variability in HPC emissions to enable the HPC industry and/or governments to advance risk-based chemical management policies in emerging markets.

Hodges|Juliet Elizabeth Natasha|JE|
Vamshi|Raghu|R|
Holmes|Christopher|C|
Rowson|Matthew|M|
Miah|Taqmina|T|
Price|Oliver Richard|OR|

Personal care products
Chemical emissions
GDP
Spatial variability


Copy-number variants in clinical genome sequencing: deployment and interpretation for rare and undiagnosed disease.

Abstract:
PURPOSE
Current diagnostic testing for genetic disorders involves serial use of specialized assays spanning multiple technologies. In principle, genome sequencing (GS) can detect all genomic pathogenic variant types on a single platform. Here we evaluate copy-number variant (CNV) calling as part of a clinically accredited GS test.

METHODS
We performed analytical validation of CNV calling on 17 reference samples, compared the sensitivity of GS-based variants with those from a clinical microarray, and set a bound on precision using orthogonal technologies. We developed a protocol for family-based analysis of GS-based CNV calls, and deployed this across a clinical cohort of 79 rare and undiagnosed cases.

RESULTS
We found that CNV calls from GS are at least as sensitive as those from microarrays, while only creating a modest increase in the number of variants interpreted (~10 CNVs per case). We identified clinically significant CNVs in 15% of the first 79 cases analyzed, all of which were confirmed by an orthogonal approach. The pipeline also enabled discovery of a uniparental disomy (UPD) and a 50% mosaic trisomy 14. Directed analysis of select CNVs enabled breakpoint level resolution of genomic rearrangements and phasing of de novo CNVs.

CONCLUSION
Robust identification of CNVs by GS is possible within a clinical testing environment.

Gross|Andrew M|AM|
Ajay|Subramanian S|SS|
Rajan|Vani|V|
Brown|Carolyn|C|
Bluske|Krista|K|
Burns|Nicole J|NJ|
Chawla|Aditi|A|
Coffey|Alison J|AJ|
Malhotra|Alka|A|
Scocchia|Alicia|A|
Thorpe|Erin|E|
Dzidic|Natasa|N|
Hovanes|Karine|K|
Sahoo|Trilochan|T|
Dolzhenko|Egor|E|
Lajoie|Bryan|B|
Khouzam|Amirah|A|
Chowdhury|Shimul|S|
Belmont|John|J|
Roller|Eric|E|
Ivakhno|Sergii|S|
Tanner|Stephen|S|
McEachern|Julia|J|
Hambuch|Tina|T|
Eberle|Michael|M|
Hagelstrom|R Tanner|RT|
Bentley|David R|DR|
Perry|Denise L|DL|
Taft|Ryan J|RJ|

rare and undiagnosed disease
microarray
copy number variation (CNV)
structural variation (SV)
whole genome sequencing (WGS)


The potential for CXCL13 in CSF as a differential diagnostic tool in central nervous system infection.

Abstract: Introduction: Central nervous system (CNS) infections can be life-threatening and are often associated with disabling sequelae. One important factor in most CNS infections is a timely pathogen-specific treatment. The diagnostic methods available, however, do not always reach a satisfying sensitivity and specificity. In these cases, there is need for additional diagnostic biomarkers. Chemokines represent potential candidates as biomarkers, since they are an important pillar of the host immune response. The aim of this review is to discuss the diagnostic potential of cerebrospinal fluid (CSF) CXCL13 in patients with CNS infections. Areas covered: Data were obtained from a literature search in PubMed up to October 2019. This review focusses on articles on the potential of CXCL13 as a diagnostic tool. The majority of identified studies aimed to characterize its role in two diseases, namely Lyme neuroborreliosis and neurosyphilis. Expert opinion: CSF CXCL13 has a significant potential as a diagnostic and monitoring add-on marker in Lyme neuroborreliosis. Differences in study design, control groups and clinical parameters between studies, however, affect sensitivity, specificity and cutoff values, underlining the need of further studies to address these issues and pave the way for a generalized clinical practice.

D002494:Central Nervous System Infections

CXCL13
central nervous system infection
Biomarker
cerebrospinal fluid
neuroborreliosis
neurosyphilis


Is the prognosis the same for periprosthetic joint infections due to Staphylococcus aureus versus coagulase-negative staphylococci? A retrospective study of 101 patients with 2-year minimum follow-up.

Abstract:
BACKGROUND
Staphylococcus aureus (SA) and Coagulase-negative staphylococci (CoNS) are often responsible for infections of total hip arthroplasty (THA) and total knee arthroplasty (TKA). One of the main differences between these two microorganisms is their virulence, with SA presumed to be more virulent; however, few studies have specifically investigated the impact of this virulence. This inspired us to carry out a retrospective study to evaluate whether the healing rate differed between SA and CoNS infections.

HYPOTHESIS
We hypothesised that the healing rate is lower for SA prosthetic joint infections.

MATERIALS AND METHODS
This was a retrospective study of 101 consecutive Staphylococcus infection cases that occurred between 2007 and 2011. There were 56 men and 45 women with an average age of 69 years (range 23-95). The infection was associated with TKA in 38 cases and THA in 63 cases. Thirty-two percent of patients had one or more comorbidities with infectious potential. In our cohort, there were 32 SA infections (31.7 %) and 69 CoNS infections (68.3 %) with 58 of the infections being methicillin-resistant (15 SA and 43 CoNS); there were 27 polymicrobial infections (26.7 %).

RESULTS
With a minimum 24-month follow-up after the end of antibiotic treatment, the healing rate was 70.3 % overall (71 patients). The healing rate was 75 % in the SA group (24 patients) versus 68.1 % (47 patients) in the CoNS group (P = 0.42).

CONCLUSION
Our hypothesis was not confirmed: the healing rate of SA prosthetic joint infections was not lower than that of CoNS infections.

LEVEL OF EVIDENCE
III, retrospective case-control study.

Murgier|J|J| Laffosse|J-M|JM| Cailliez|J|J| Cavaignac|E|E| Murgier|P|P| Bayle-Iniguez|X|X| Chiron|P|P| Bonnevialle|P|P|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D000900:Anti-Bacterial Agents
D019644:Arthroplasty, Replacement, Hip
D019645:Arthroplasty, Replacement, Knee
D016022:Case-Control Studies
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D007595:Joint Prosthesis
D008297:Male
D008875:Middle Aged
D011379:Prognosis
D016459:Prosthesis-Related Infections
D012189:Retrospective Studies
D013203:Staphylococcal Infections
D013211:Staphylococcus aureus
D014945:Wound Healing

Periprosthetic joint infection
Total hip arthroplasty
Total knee arthroplasty
Staphylococcus spp.


Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter.

Abstract: Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4(+) T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.

Ji|Young Rae|YR|
Kim|Hei Jung|HJ|
Yu|Dong Hun|DH|
Bae|Ki Beom|KB|
Park|Seo Jin|SJ|
Park|Si Jun|SJ|
Jang|Woo Young|WY|
Kang|Min-Cheol|MC|
Jeong|Jain|J|
Sung|Yong Hun|YH|
Choi|Minjee|M|
Park|Taejun|T|
Park|Taesun|T|
Yun|Jong Won|JW|
Lee|Hyun-Shik|HS|
Lee|Sanggyu|S|
Kim|Myoung Ok|MO|
Ryoo|Zae Young|ZY|

D056486:Chemical and Drug Induced Liver Injury

Roquin
Hepatitis
Transgenic mice
Concanavalin A
T cell activation


Development of an Improved T-cell Assay to Assess the Intrinsic Immunogenicity of Haptenic Compounds.

Abstract: The prediction of drug hypersensitivity is difficult due to the lack of appropriate models and known risk factors. In vitro naïve T-cell priming assays that assess immunogenicity have been developed. However, their application is limited due requirements for 2 batches of autologous dendritic cells (DC) and inconsistent results; a consequence of single well readouts when exploring reactions where compound-specific T-cell frequency is undefined. Hence, we aimed to develop an improved, but simplified assay, termed the T-cell multiple well assay (T-MWA), that permits assessment of drug-specific activation of naïve T cells, alongside analysis of the strength of the induced response and the number of cultures that respond. DC naïve T-cell coculture, depleted of regulatory T cells (Tregs), was conducted in up to 48 wells for 2 weeks with model haptens (nitroso sulfamethoxazole [SMX-NO], Bandrowski's base [BB], or piperacillin [PIP]). Cultures were rechallenged with hapten and T-cell proliferation was measured using [3H]-thymidine incorporation. Priming of naïve T cells was observed with SMX-NO, with no requirement for DC during restimulation. Greater than 65% of cultures were activated with SMX-NO; with 8.0%, 30.8%, and 27.2% characterized as weak (stimulation index [SI] =1.5-1.9), moderate (SI = 2-3.9), and strong responses (SI > 4), respectively. The number of responding cultures and strength of the response was reproducible when separate blood donations were compared. Coinhibitory checkpoint blockade increased the strength of the proliferative response, but not the number of responding cultures. Moderate to strong priming responses were detected with BB, whereas PIP stimulated only a small number of cultures to proliferate weakly. In drug-responsive cultures inducible CD4+CD25+FoxP3+CD127low Tregs were also identified. To conclude, the T-MWA offers improvements over existing assays and with development it could be used to study multiple HLA-typed donors in a single plate format.

Ogese|Monday O|MO|
Watkinson|Joel|J|
Lister|Adam|A|
Faulkner|Lee|L|
Gibson|Andrew|A|
Hillegas|Aimee|A|
Sakatis|Melanie Z|MZ|
Park|Brian Kevin|BK|
Naisbitt|Dean J|DJ|

drug hypersensitivity
human
immune system


Integrated Assessment of Coastal Exposure and Social Vulnerability to Coastal Hazards in East Africa.

Abstract:
An index of vulnerability to coastal change, integrating indices of social vulnerability and exposure to coastal hazards, was created for East Africa to identify 'areas of priority concern' for risk reduction. Currently, 22% of East Africa's coastline and 3.5 million people are at higher levels of exposure to coastal hazards, which would increase, respectively, to 39% and 6.9 million people if mangroves, coral reefs and seagrasses are lost. Madagascar and Mozambique show the largest proportion of the coastline at higher exposure, while Kenya and Tanzania benefit the most from natural coastal protection. Coral reefs protect 2.5 million people from higher exposure, mostly in Mombasa, Zanzibar and Dar es Salaam. Considering Mozambique, Kenya and Tanzania, the latter is the least, and the former is the most vulnerable. Under current conditions, 17 (out of 86) coastal districts are considered 'areas of priority concern'; four of these are critically exposed as over 90% of their shoreline length are at higher exposure (Zavala, Inharrime, Manhiça and Mandlakaze, all in southern Mozambique). These locations are of critical concern for any present or future coastal development due to the high level of exposure posed to both vulnerable people and investments. Habitat loss would increase the number of 'priority concern' districts to 24; some would show great increase in the population exposed (e.g. Pemba and Mossuril in Mozambique). Applying this knowledge to identify where ecosystem-based management should be prioritised to promote social and environmental resilience is timely and urgent in East Africa.

Supplementary Information
The online version contains supplementary material available at 10.1007/s12237-021-00930-5.

Exposure
Vulnerability
Coastal hazards
East Africa
Index
Ecosystem-based management


Lee Robins' studies of heroin use among US Vietnam veterans.

Abstract: The work of Robins and her colleagues on heroin addiction among Vietnam veterans sets out in microcosm many of the key factors that play out in the development and maintenance of substance addiction beyond the pharmacology of the drug: price, availability, the process of delivery of the addictive substance, availability of other substances, social norms, education and life circumstances. Robins' studies found high rates of heroin use (34%) and symptoms of heroin dependence (20%) among US soldiers while serving in Vietnam. In the first year after returning to the United States only 1% became re-addicted to heroin, although 10% tried the drug after their return. Like other seminal studies, this work needs to be read in the original, because relying upon secondary interpretations risks being given a selectively edited version of their findings in service of varied policy and theoretical agendas.

Robins heroin Vietnam Addiction policy relapse


Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study.

Abstract:
BACKGROUND
Recent studies showed that lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease (CVD). However, whether Lp(a) modifies clinical risk assessment was not established.

OBJECTIVES
This study was conducted to determine whether Lp(a) improves CVD risk prediction.

METHODS
In 1995, Lp(a) was measured in 826 men and women (age range, 45 to 84 years) from the general community. Incidence of CVD was recorded over 15 years of follow-up.

RESULTS
In models adjusted for Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) variables, the hazard ratio (HR) for incident CVD was 1.37 per 1-SD higher Lp(a) level (SD = 32 mg/dl) and 2.37 when comparing the top fifth quintile with other quintiles. The addition of Lp(a) to the RRS increased the C-index by 0.016. Of the 502 subjects who remained free of CVD, 82 were correctly reclassified to a lower risk category and 49 were reclassified to a higher risk category (predicted 15-year categories: <7.5%, 7.5% to <15%, 15% to <30%, ≥30%) (p < 0.001). Of the 148 subjects who developed CVD, 18 were correctly reclassified to a higher risk category and 17 were reclassified to a lower risk category. In subjects at intermediate risk (15% to <30%), the net reclassification improvement afforded by Lp(a) was 22.5% for noncases, 17.1% for cases, and 39.6% overall. Allele-specific Lp(a) levels did not add to the predictive ability of the FRS or RRS or to Lp(a).

CONCLUSIONS
Elevated Lp(a) predicts 15-year CVD outcomes and improves CVD risk prediction. These findings suggest that Lp(a) levels may be used in risk assessment of subjects in the general community, particularly in intermediate-risk groups.

Willeit|Peter|P|
Kiechl|Stefan|S|
Kronenberg|Florian|F|
Witztum|Joseph L|JL|
Santer|Peter|P|
Mayr|Manuel|M|
Xu|Qingbo|Q|
Mayr|Agnes|A|
Willeit|Johann|J|
Tsimikas|Sotirios|S|

atherosclerosis
autoantibodies
lipoproteins
oxidation
oxidation-specific epitopes
oxidized phospholipids


Concepts in context: Processing mental state concepts with internal or external focus involves different neural systems.

Abstract: According to embodied cognition theories, concepts are contextually situated and grounded in neural systems that produce experiential states. This view predicts that processing mental state concepts recruits neural regions associated with different aspects of experience depending on the context in which people understand a concept. This neuroimaging study tested this prediction using a set of sentences that described emotional (e.g., fear, joy) and nonemotional (e.g., thinking, hunger) mental states with internal focus (i.e., focusing on bodily sensations and introspection) or external focus (i.e., focusing on expression and action). Consistent with our predictions, data suggested that the inferior frontal gyrus, a region associated with action representation, was engaged more by external than internal sentences. By contrast, the ventromedial prefrontal cortex, a region associated with the generation of internal states, was engaged more by internal emotion sentences than external sentence categories. Similar patterns emerged when we examined the relationship between neural activity and independent ratings of sentence focus. Furthermore, ratings of emotion were associated with activation in the medial prefrontal cortex, whereas ratings of activity were associated with activation in the inferior frontal gyrus. These results suggest that mental state concepts are represented in a dynamic way, using context-relevant interoceptive and sensorimotor resources.

Oosterwijk|Suzanne|S|
Mackey|Scott|S|
Wilson-Mendenhall|Christine|C|
Winkielman|Piotr|P|
Paulus|Martin P|MP|

Mental states
Embodiment
Emotion
IFG
Simulation
vmPFC


Morcellation in gynecology: short review and suggestions from Turkish Society of Minimally Invasive Gynecologic Oncology

Abstract: Morcellation allows the removal of a large uterus and fibroids through small incisions with minimally invasive surgery. It helps to prevent the complications associated with large incisions in both hysterectomy and myomectomy operations. Currently, there is much debate regarding the use of power morcellation in laparoscopic hysterectomy and myomectomy, mainly due to the risk of peritoneal dissemination of undiagnosed uterine sarcomas. Unfortunately, there is no valid pre-operative diagnostic method that can differentiate sarcomas from myomas, and the currently available scientific literature regarding morcellation is insufficient. As the Turkish Society of Minimally Invasive Gynecological Oncology, we present our consensus opinion and suggestions for the preoperative evaluation and morcellation of fibroids, in line with the recent literature.

morcellation
hysterectomy
Myomectomy
laparoscopic surgery
vaginal surgery


Single Image Super-Resolution Based on Global Dense Feature Fusion Convolutional Network.

Abstract: Deep neural networks (DNNs) have been widely adopted in single image super-resolution (SISR) recently with great success. As a network goes deeper, intermediate features become hierarchical. However, most SISR methods based on DNNs do not make full use of the hierarchical features. The features cannot be read directly by the subsequent layers, therefore, the previous hierarchical information has little influence on the subsequent layer output, and the performance is relatively poor. To address this issue, a novel global dense feature fusion convolutional network (DFFNet) is proposed, which can take full advantage of global intermediate features. Especially, a feature fusion block (FFblock) is introduced as the basic module. Each block can directly read raw global features from previous ones and then learns the feature spatial correlation and channel correlation between features in a holistic way, leading to a continuous global information memory mechanism. Experiments on the benchmark tests show that the proposed method DFFNet achieves favorable performance against the state-of-art methods.

Xu|Wang|W| Chen|Renwen|R| Huang|Bin|B| Zhang|Xiang|X| Liu|Chuan|C|

image super-resolution
dense feature fusion
convolutional neural network


Peroral endoscopic myotomy: Time to change our opinion regarding the treatment of achalasia?

Abstract: Peroral endoscopic myotomy (POEM) is a new endoscopic treatment for achalasia. Compared to the classical surgical myotomy, POEM brings at least the advantage of minimal invasiveness. The data provided until now suggest that POEM offers excellent short-term symptom resolution, with improvement of dysphagia in more than 90% of treated patients, with encouraging manometric outcomes and low incidence of postprocedural gastroesophageal reflux. The effectiveness of this novel therapy requires long-term follow-up and comparative studies with other treatment modalities for achalasia. This technique requires experts in interventional endoscopy, with a learning curve requiring more than 20 cases, including training on animal and cadaver models, and with a need for structured proctoring during the first cases. This review aims to summarize the data on the technique, outcomes, safety and learning curve of this new endoscopic treatment of achalasia.

Peroral endoscopic myotomy
Myotomy
Achalasia
Endoscopic treatment


Estimating the Quality of 3D Protein Models Using the ModFOLD7 Server.

Abstract: Assessing the accuracy of 3D models has become a keystone in the protein structure prediction field. ModFOLD7 is our leading resource for Estimates of Model Accuracy (EMA), which has been upgraded by integrating a number of the pioneering pure-single- and quasi-single-model approaches. Such an integration has given our latest version the strengths to accurately score and rank predicted models, with higher consistency compared to older EMA methods. Additionally, the server provides three options for producing global score estimates, depending on the requirements of the user: (1) ModFOLD7_rank, which is optimized for ranking/selection, (2) ModFOLD7_cor, which is optimized for correlations of predicted and observed scores, and (3) ModFOLD7 global for balanced performance. ModFOLD7 has been ranked among the top few EMA methods according to independent blind testing by the CASP13 assessors. Another evaluation resource for ModFOLD7 is the CAMEO project, where the method is continuously automatically evaluated, showing a significant improvement compared to our previous versions. The ModFOLD7 server is freely available at http://www.reading.ac.uk/bioinf/ModFOLD/ .

Maghrabi|Ali H A|AHA|
McGuffin|Liam J|LJ|

D056004:Molecular Dynamics Simulation
D011487:Protein Conformation
D020539:Sequence Analysis, Protein
D012984:Software

Continuously evaluate the accuracy and reliability of predictions (CAMEO)

Critical assessment of techniques for protein structure prediction (CASP)


Type 2 Diabetes Mellitus Is Associated with Social Recognition Memory Deficit and Altered Dopaminergic Neurotransmission in the Amygdala.

Abstract:
Objective
Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes mellitus (DM). It is now established that DM causes various CNS complications like Alzheimer's, dementia, anxiety, depression, neurodegeneration, mood disorders, cognitive dysfunctioning, and so on. Since amygdala and dopaminergic circuitry are critical in controlling several aspects of social behavior, even social recognition memory (SRM), we aimed to study the expression analysis of dopaminergic circuitry in amygdala using real-time polymerase chain reaction.

Material and Methods
Animals were divided into 2 age- and weight-matched groups: group I-control group and group II-diabetic group. Diabetes was induced by injecting 50 mg/kg streptozotocin (STZ; in 0.1 mL ice cold citrate buffer, pH 4.5) i.p. for 5 consecutive days. Behavioral tests were performed 8 weeks after diabetes was introduced. On day 60, animals were sacrificed, amygdala was dissected, and the total RNA was isolated. Expression analysis was carried out using real time PCR.

Results
No significant changes were observed in social interaction and social isolation aspects of diabetic mice, but SRM was significantly dysregulated. Additionally, we found that dopaminergic neurotransmission (dopaminergic receptor expression and expression of enzymes controlling dopamine turnover) was significantly downregulated in the amygdala of STZ mice as compared to controls.

Conclusion
We hypothesize that the altered SRM could be due to the dysregulated dopaminergic circuitry in amygdala, although a detailed investigation is required to establish a causal relationship.

Diabetes mellitus
Social recognition memory
Amygdala
Dopaminergic receptors
Dopamine turnover


Evolutions of gas temperature inside fire compartment and external facade flame height with a casement window.

Abstract: Gas temperature of a fire compartment and external facade flame height pose serious hazard upon urban environment and safety, where the window (ventilation) condition has an essential impact. This paper investigates their evolutions with a casement window of various opening angles, which has not been quantified previously although is commonly used practically. Experiments are conducted employing a model-scale fire compartment under different heat release rates with a casement window of various dimensions and opening angles. It is found that the upper-part gas temperature inside the compartment increases, while the critical heat release rate for flame ejection as well as the external facade flame height decreases, with increasing of the window opening angle as it is less than 60 degrees (θ < 60°). Then, all these quantities change little as the window opening angle is further increased (θ ≥ 60°). New non-dimensional models are proposed to describe the evolutions of these quantities based on the derived new length scale according to window dimensions and opening angle. This paper provides for the first time both essential data and new correlations for the gas temperature inside fire compartment and external facade flame height with a casement window.

Sun|Xiepeng|X| Hu|Longhua|L| Yang|Yong|Y| Ren|Fei|F| Fang|Xiang|X|

Facade flame
Casement window
Compartment fire
Gas temperature inside compartment
Urban fire hazard and safety


Rehabilitation of a Patient with Facial and Palatal Defect - A Case Report.

Abstract: Defects involving the face and maxilla present a challenge to the prosthodontists as these have a direct effect on aesthetics, function as well as the psychology of the patient. An array of problems awaits the clinician from restoring the previous contour of the oral cavity, facial form, etc. to the mental state of the patients. This article deals with the rehabilitation of a hemimaxillectomy patient with a facial defect, using an interim hollow bulb obturator and a silicone facial prosthesis, which helped to improve the general well being of the patient. Rehabilitative procedures provide patients considerable care so that they can continue their life with confidence.

Hemimaxillectomy
Hollow bulb obturator
Facial silicone prosthesis


A new perspective on the value of minimally invasive colorectal surgery-payer, provider, and patient benefits.

Abstract:
BACKGROUND
The clinical benefits of minimally invasive surgery (MIS) are proven, but overall financial benefits are not fully explored. Our goal was to evaluate the financial benefits of MIS from the payer's perspective to demonstrate the value of minimally invasive colorectal surgery.

METHODS
A Truven MarketScan® claim-based analysis identified all 2013 elective, inpatient colectomies. Cases were stratified into open or MIS approaches based on ICD-9 procedure codes; then costs were assessed using a similar distribution across diagnosis related groups (DRGs). Care episodes were compared for average allowed costs, complication, and readmission rates after adjusting costs for demographics, comorbidities, and geographic region.

RESULTS
A total of 4615 colectomies were included-2054 (44.5 %) open and 2561 (55.5 %) MIS. Total allowed episode costs were significantly lower MIS than open ($37,540 vs. $45,284, p < 0.001). During the inpatient stay, open cases had significantly greater ICU utilization (3.9 % open vs. 2.0 % MIS, p < 0.001), higher overall complications (52.8 % open vs. 32.3 % MIS, p < 0.001), higher colorectal-specific complications (32.5 % open vs. 17.9 % MIS, p < 0.001), longer LOS (6.39 open vs. 4.44 days MIS, p < 0.001), and higher index admission costs ($39,585 open vs. $33,183 MIS, p < 0.001). Post-discharge, open cases had significantly higher readmission rates/100 cases (11.54 vs. 8.28; p = 0.0013), higher average readmission costs ($3055 vs. $2,514; p = 0.1858), and greater 30-day healthcare costs than MIS ($5699 vs. $4357; p = 0.0033). The net episode cost of care was $7744/patient greater for an open colectomy, even with similar DRG distribution.

CONCLUSIONS
In a commercially insured population, the risk-adjusted allowed costs for MIS colectomy episodes were significantly lower than open. The overall cost difference between MIS and open was almost $8000 per patient. This highlights an opportunity for health plans and employers to realize financial benefits by shifting from open to MIS for colectomy. With increasing bundled payment arrangements and accountable care sharing programs, the cost impact of shifting from open to MIS introduces an opportunity for cost savings.

Keller|Deborah S|DS|
Senagore|Anthony J|AJ|
Fitch|Kathryn|K|
Bochner|Andrew|A|
Haas|Eric M|EM|

D019060:Minimally Invasive Surgical Procedures

Financial benefits
Minimally invasive colorectal surgery
Cost shifting
Healthcare outcomes
Open colorectal surgery


Efficient expression of SRK intracellular domain by a modeling-based protein engineering.

Abstract: S-locus protein kinase (SRK) is a receptor kinase that plays a critical role in self-recognition in the Brassicaceae self-incompatibility (SI) response. SRK is activated by binding of its ligand S-locus protein 11 (SP11) and subsequently induced phosphorylation of the intracellular kinase domain. However, a detailed activation mechanism of SRK is still largely unknown because of the difficulty in stably expressing SRK recombinant proteins. Here, we performed modeling-based protein engineering of the SRK kinase domain for stable expression in Escherichia coli. The engineered SRK intracellular domain was expressed about 54-fold higher production than wild type SRK, without loss of the kinase activity, suggesting it could be useful for further biochemical and structural studies.

Murase|Kohji|K| Hirano|Yoshinori|Y| Takayama|Seiji|S| Hakoshima|Toshio|T|

D017360:Arabidopsis
D015870:Gene Expression
D008958:Models, Molecular
D010940:Plant Proteins
D000072417:Protein Domains
D015202:Protein Engineering
D011494:Protein Kinases
D011994:Recombinant Proteins

Protein engineering
Protein kinase
Self-incompatibility
Stable expression