bluuebunny/crossref_metadata_2025 huggingface dataset:
The community burden of surgical site infection following elective colorectal resection
Authors: Newton Lydia , Dewi Ffion , McNair Angus , Gane Dawn , Rogers Jodie , Dean Harry , Pullyblank Anne
Published: November 2020

Aim

Surgical site infection (SSI) is common after colorectal surgery. Recent attempts to measure SSI have focused on inpatient SSI and readmissions. This study examined patient‐reported SSI at 30 days over 8 years.

Methods

The Health Protection Agency questionnaire was used to prospectively measure 30‐day patient‐reported SSI in patients undergoing elective colorectal operations between February 2011 and April 2019. Questionnaires were sent by post and followed up with a phone call. Data relating to hospital stay were prospectively recorded on an enhanced recovery database.

Results

In all, 80.7% (1268) of 1559 patients responded to the questionnaire with an overall SSI rate of 15.9% (201/1268). The majority of patients who reported SSI presented in the community (66.7%) of whom 65% consulted their general practitioner and 35% saw a community nurse. Patient‐reported SSI was validated by a health professional in over 90% of cases. Overall, only 1.5% of readmissions and 2% of ward attendances were due to an isolated wound problem. Patients who developed SSI during their index admission had a longer length of stay (11 days vs. 4 days) but there was no difference in delayed discharge or complications between patients with and without SSI, suggesting that a previously described association between SSI and increased length of stay may be due to observational bias.

Conclusion

Existing surveillance audits are suboptimal for monitoring SSIs following colorectal surgery as most SSIs present after discharge. There is a need for robust 30‐day surveillance with a standardized methodology if comparisons are to be made between units.
The influence of child maltreatment on substance or alcohol use in 30‐year‐old adults: A birth cohort study
Authors: Kisely Steve , Strathearn Lane , Najman Jake
Published: November 2020

Introduction and Aims

Retrospective studies have shown a strong association between experiencing maltreatment in childhood and subsequent illicit substance or alcohol use. Prospective studies are rarer, with limited data following subjects into adulthood. We report findings from a prospective record‐linkage analysis, which examines whether notified and/or substantiated child maltreatment is associated with substance (SUD) or alcohol use disorders (AUD) in early adulthood when participants are 30 years old.

Design and Methods

We linked data from a statutory child protection agency of prospectively notified and substantiated child maltreatment to a survey of a birth cohort recruited from the main maternity hospital of Brisbane. The main outcomes were 30‐day and lifetime diagnoses of SUD or AUD at 30‐year follow‐up as measured by the Composite International Diagnostic Interview, Auto version.

Results

Of the 2861 people at the 30‐year follow‐up, 103 (3.6%) had a history of agency‐substantiated maltreatment by 16 years. On adjusted analyses, AUD in the previous 30 days or lifetime SUD were both significantly associated with childhood maltreatment. Of maltreatment subtypes, 30‐day AUD at 30 years of age was particularly associated with physical and emotional abuse while SUD was associated with sexual maltreatment. Recurring or multiple forms of abuse had the worst outcomes.

Discussion and Conclusions

Child maltreatment, especially involving physical and sexual abuse, predicts AUD and SUD that extends to people in their 30s. Children with more than one type of maltreatment are at particular risk. Further research may help to identify possible predictors of long‐term outcomes of child maltreatment.
Quality of life in children with cerebral palsy: don’t forget to ask the child
Authors: Harris Angela
Published: November 2020

This commentary is on the original article by Sentenac et al. on pages 68–74 of this issue.
Novel insight from the first lung transplant of a COVID‐19 patient
Authors: Chen Xiao‐Jun , Li Kai , Xu Lei , Yu You‐Jia , Wu Bo , He Yuan‐Lin , Zhao Wen‐E. , Li Ding , Luan Chang‐Xing , Hu Li , Wang Jie , Ding Jing‐Jing , Yu Yan‐Fang , Li Jing‐Xin , Tan Zhong‐Ming , Liu Xiao‐Fei , Wei Dong , Zhang Zhi‐Hong , Guo Xue‐Jiang , Su Chuan , Hu Zhi‐Bin , Guo Yue‐Shuai , Chen Jing‐Yu , Chen Feng
Published: November 2020

Background

To reveal detailed histopathological changes, virus distributions, immunologic properties and multi‐omic features caused by SARS‐CoV‐2 in the explanted lungs from the world's first successful lung transplantation of a COVID‐19 patient.

Materials and methods

A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID‐19‐associated pulmonary fibrosis.

Results

The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+CD4− T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL‐1β and IL‐6 were in the area of mild fibrosis. Multi‐omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation.

Conclusions

Our results provide novel insight that the significant neutrophil/ CD3+CD4− T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID‐19 patient and may contribute to a better understanding of COVID‐19 pathogenesis.
Decreased 14‐3‐3 expression correlates with age‐related regional reductions in CNS dopamine and motor function in the pond snail, Lymnaea
Authors: Morgan Lindsay D. , Mohammed Aiyaz , Patel Bhavik Anil , Arundell Martin , Jennert‐Burtson Katrin , Hernádi László , Overall Andrew , Bowler Lucas D. , O'Hare Danny , Yeoman Mark S.
Published: November 2020

Ageing is associated in many organisms with a reduction in motor movements. We have previously shown that the rate of feeding movements of the pond snail, Lymnaea, decreased with age but the underlying cause is not fully understood. Here, we show that dopamine in the cerebro‐buccal complex is an important signalling molecule regulating feeding frequency in Lymnaea and that ageing is associated with a decrease in CNS dopamine. A proteomic screen of young and old CNSs highlighted a group of proteins that regulate stress responses. One of the proteins identified was 14‐3‐3, which can enhance the synthesis of dopamine. We show that the Lymnaea 14‐3‐3 family exists as three distinct isoforms. The expression of the 29 kDa isoform (14‐3‐3Lym3) in the cerebro‐buccal complex decreased with age and correlated with feeding rate. Using a 14‐3‐3 antagonist (R18) we were able to reduce the synthesis of L‐DOPA and dopamine in ex vivo cerebro‐buccal complexes. Together these data suggest that an age‐related reduction in 14‐3‐3 can decrease CNS dopamine leading to a consequential reduction in feeding rate.
Co‐incidental C9orf72 expansion mutation‐related frontotemporal lobar degeneration pathology and sporadic Creutzfeldt−Jakob disease
Authors: Klotz Sigrid , König Theresa , Erdler Marcus , Ulram Andreas , Nguyen Anita , Ströbel Thomas , Zimprich Alexander , Stögmann Elisabeth , Regelsberger Günther , Höftberger Romana , Budka Herbert , Kovacs Gabor G. , Gelpi Ellen
Published: November 2020

Background

The C9orf72 hexanucleotide expansion mutation is the most common cause of genetic frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and combined FTD‐ALS. Its underlying neuropathology combines TDP‐43 pathology and dipeptide repeat protein (DPR) deposits and may also associate with other neurodegeneration‐associated protein aggregates. Herein we present a unique combination of C9orf72 mutation with sporadic Creutzfeldt−Jakob disease (CJD) in a 74‐year‐old patient with rapidly progressive dementia.

Methods

Detailed neuropathological examination including immunohistochemistry for several proteinopathies. Genetic analysis was conducted by repeat primed polymerase chain reaction (PCR). Furthermore, we analyzed additional C9orf72 mutation carriers for prion−protein (PrP) deposits in brain tissue and screened the cerebellar cortex of other CJD cases for p62/DPR neuronal inclusions to assess the frequency of combined pathologies.

Results

Postmortem brain examination of a patient with a rapidly progressive neurological deterioration of 8 months’ duration confirmed the diagnosis of CJD. She harbored valine homozygosity at PRNP codon 129. In addition, a frontotemporal lobar degeneration (FTLD)‐pattern with TDP‐43 protein aggregates and p62+/C9RANT+ positive inclusions along with a high degree of Alzheimer‐related pathology (A3B3C3) were identified. The suspected C9orf72 expansion mutation was confirmed by repeat‐primed PCR. Screening of 13 C9orf72 cases showed no pathological PrP aggregates and screening of 100 CJD cases revealed no other C9orf72 expansion mutation carriers.

Conclusion

A combination of a C9orf72 expansion mutation‐related FTLD with sporadic CJD in the same patient is rare. While the rarity of both diseases makes this concurrence most likely to be coincidental, questions regarding a potential link between these two neurodegenerative pathologies deserve further studies.
β‐Amyloid may accumulate in the human brain after focal bacterial infection: An 18F‐flutemetamol positron emission tomography study
Authors: Rogne Ane Gretesdatter , Müller Ebba Gløersen , Udnæs Eirin , Sigurdardottir Solrun , Raudeberg Rune , Connelly James Patrick , Revheim Mona‐Elisabeth , Hassel Bjørnar , Dahlberg Daniel
Published: November 2020

Background and purpose

β‐Amyloid formation has been suggested to form part of the brain's response to bacterial infection. This hypothesis has been based on experimental animal studies and autopsy studies in humans. We asked if β‐amyloid accumulates locally around a bacterial brain abscess in living human patients. Furthermore, because brain abscess patients may suffer from chronic cognitive symptoms after abscess treatment, we also asked if a brain abscess precipitates accumulation of β‐amyloid in the neocortex in a manner that could explain abscess‐related cognitive complaints.

Methods

In a prospective study, we investigated 17 brain abscess patients (age 24–72 years) with 18F‐flutemetamol positron emission tomography on one occasion 1 to 10 months after brain abscess treatment to visualize β‐amyloid accumulation.

Results

18F‐flutemetamol uptake was reduced in the edematous brain tissue that surrounded the abscess remains. On this background of reduced 18F‐flutemetamol signal, three out of 17 patients showed a distinctly increased 18F‐flutemetamol uptake in the tissue immediately surrounding the abscess remains, suggesting accumulation of β‐amyloid. These three patients underwent 18F‐flutemetamol positron emission tomography significantly earlier after neurosurgical treatment (p = 0.042), and they had larger abscesses (p = 0.027) than the rest of the patients. All 17 patients suffered from mental fatigue or some subjective cognitive symptom, such as attention difficulties or memory problems, but in none of the patients was there an increase in neocortical 18F‐flutemetamol signal.

Conclusions

β‐Amyloid may accumulate locally around the abscess remains in some patients with a brain abscess.
Effect of vitamin D and/or omega‐3 fatty acid supplementation on stroke outcomes: A randomized trial
Authors: Rist Pamela M. , Buring Julie E. , Cook Nancy R. , Manson JoAnn E. , Rexrode Kathryn M.
Published: November 2020

Background and purpose

Among stroke patients, low serum 25‐hydroxyvitamin D predicts poor outcomes. In mice, higher omega‐3 (n‐3) fatty acid intake diminishes brain damage after stroke. In this study, we tested whether vitamin D or n‐3 fatty acids supplementation prior to stroke reduces the risk of functional limitations and physical disability after stroke.

Methods

We used data from VITAL (the VITamin D and OmegA‐3 TriaL) which randomized middle‐aged and older men and women without cardiovascular disease to vitamin D3 (2000 IU/day) and/or marine n‐3 fatty acids (1 g/day) and followed them for incident stroke events. Individuals experiencing a non‐fatal stroke were mailed questionnaires assessing functional limitations (the physical performance scale adapted from Nagi) and physical disability (the modified Katz Activities of Daily Living and Rosow‐Breslau Functional Health scales). We used logistic regression to analyze associations between randomized treatment and limitations on each scale.

Results

A total of 290 individuals experienced their first stroke during the trial, of whom 197 stroke survivors completed the stroke outcomes questionnaire a median of 1.4 years after diagnosis. We observed no associations between randomized treatment to vitamin D and functional limitations (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.52, 1.97) or physical disability (Rosow‐Breslau scale: OR 0.92, 95% CI 0.50, 1.67; Katz scale: OR 1.03, 95% CI 0.31, 3.42). Those randomized to n‐3 fatty acids had a non‐significantly lower risk of functional limitations (OR 0.55, 95% CI 0.28, 1.09) and physical disability (Rosow‐Breslau scale: OR 0.56, 95% CI 0.31, 1.02; Katz sclae: OR 0.32, 95% CI 0.50, 1.67).

Conclusion

Vitamin D or omega‐3 fatty acid supplementation prior to stroke did not result in significantly improved post‐stroke outcomes.
Quantitative and qualitative analysis of operator inhaled aerosols during routine motorised equine dental treatment
Authors: Bescoby Sam R. , Davis Sean A. , Sherriff Martyn , Ireland Anthony J.
Published: November 2020

Background

Routine equine odontoplasty is performed by both Veterinary Surgeons and Equine Dental Technicians. The production of aerosolised particulates from motorised equipment has been well documented in human orthodontics but has yet to be investigated in the veterinary industry.

Objectives

To assess the size, quantity and composition of particulates produced during routine motorised odontoplasty and to model their deposition in the human respiratory tree.

Study design

Analytic observational study.

Methods

Fifteen‐minute routine motorised odontoplasties were performed on cadaver heads with monitoring equipment placed 30 cm away from the oral cavity to simulate the position of the operator's face. For quantitative analysis, an active air sampling photometric monitor was used to detect the concentration of fully respirable (<4.25 µm) particles produced. The use of water and non–water‐cooled equipment and 2 different types of face mask (standard surgical and FFP3) were compared. An 8‐stage Marple Personal Cascade Impactor modelled the deposition of the particulates in relation to the human respiratory tree. Qualitative analysis of these particulates was performed using scanning electron microscopy and energy dispersive x‐ray spectroscopy.

Results

Motorised odontoplasty created aerosolised particulates that could reach all levels of the human respiratory tree. These particulates were composed mostly of calcium and phosphate, although traces of metals were found. The concentration of fully respirable particulates exceeded the recommended exposure limits set by the Health and Safety Executive. The use of an FFP‐3 face mask significantly reduced the level of inhaled particulates.

Main limitations

This was a simulated experiment. It does not take into account the variety of environments in which routine treatment takes place.

Conclusions

There are possible health risks in performing a large amount of routine motorised dentistry due to inhalation of aerosolised particulates. The use of an adequate face mask lowers exposure levels to within acceptable limits and, therefore, should be worn.
The role of Dipeptidyl Peptidase‐4 in cutaneous disease
Authors: Patel Payal M. , Jones Virginia A. , Kridin Khalaf , Amber Kyle T.
Published: November 2020

Dipeptidyl peptidase‐4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T‐cell biology, the induction of skin‐specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin‐1, CXCR4 receptor, M6P/insulin‐like growth factor II‐receptor and fibroblast activation protein‐α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1‐like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.
Expression of antimicrobial peptide genes oscillates along day/night rhythm protecting mice skin from bacteria
Authors: Bilska Bernadetta , Zegar Aneta , Slominski Andrzej T. , Kleszczyński Konrad , Cichy Joanna , Pyza Elzbieta
Published: November 2020

Antimicrobial peptides (AMPs) are important components of the innate immune system and are involved in skin protection against environmental insults and in wound healing. Herein, we assessed the gene expression of chemerin (Rarres2), cathelicidin CRAMP (Camp), and three β‐defensins (Defb1, Defb3, and Defb14) in mouse skin during light/dark cycle (LD 12:12) and constant darkness (DD). Next, we examined the survival of bacteria applied on the skin at specific times during the day. We found that the expression of Rarres2, Camp, and Defb1 was the highest at 4 h after the beginning of darkness, during high activity of mice. These rhythms, however, were not maintained under DD in the skin but were present in the liver. This indicated that in the case of skin, a circadian input was masked by daily changes of light in the environment. In contrast, Defb3 and Defb14 showed the highest mRNA levels when the mice slept, and these rhythmic mRNA oscillations were maintained under DD. This shows that Rarres2, Camp, and Defb1 levels in the skin are correlated with high locomotor activity in mice and they are controlled by daily changes of light and dark. Alternatively, oscillations in the mRNA levels of Defb3 and Defb14 seem to protect skin and heal wounds during sleep. These rhythms are maintained under DD, indicating that they are regulated by a circadian clock. Our study suggests that daily AMP expression affects the survival of bacteria on the surface of skin, which depends on the phase of AMP cycling.
Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models
Authors: Yoshida Ayaka , Yamamoto Kazuhiro , Ishida Takahiro , Omura Tomohiro , Itoh Tomoo , Nishigori Chikako , Sakane Toshiyasu , Yano Ikuko
Published: November 2020

Hand–foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the molecular biological mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatological and biological abnormalities induced by sunitinib. On the basis of the results of microarray analysis using the three‐dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal‐type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochemical staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal‐regulated kinases (ERK)1/2 and phosphorylated p38 mitogen‐activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib‐induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase‐3β by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathology of HFSR.
A review of cassava semolina (gari and eba) end‐user preferences and implications for varietal trait evaluation
Authors: Awoyale Wasiu , Alamu Emmanuel Oladeji , Chijioke Ugo , Tran Thierry , Takam Tchuente Hubert Noel , Ndjouenkeu Robert , Kegah Ngoualem , Maziya‐Dixon Busie
Published: November 2020

The purpose of this review is to support breeders and food scientists by examining research carried out on end‐user preferences for gari and its derived dough product, eba, in Africa. The review focused on gari regarding the physical and chemical composition of raw cassava roots, methods of storage, the composition of gari with or without enrichment, and the sensory evaluation of gari and eba. The primary sensory attributes identified to describe gari are colour, taste, texture, aroma and flavour. Texture attribute of importance is crispiness for uncooked gari, and hand feel before consumption for eba. There was a significant correlation between the sensory characteristics of gari and the starch and cyanogenic potential (CNP) contents of the raw roots. Hence, the correlation of the end‐user preferences with the chemical composition of the cassava roots could be helpful to breeders in refining selection criteria and developing high‐throughput screening methods.
The interaction between inulin and wheat starch and effects of inulin on frozen storage quality of noodles
Authors: Xu Fei , Li XueQin , Li Jia‐Heng , Chen Jie
Published: November 2020

In this paper, the effects of adding a different proportion of inulin powder on starch gelatinisation, free amylose content, thermodynamic properties and microstructure of wheat starch were studied. RVA results showed that the addition of inulin could increase the starting temperature of wheat starch gelatinisation, decrease the peak viscosity and the setback value, and reduce the content of the leached amylose. In DSC test, similar trend was observed, starting temperature and peak temperature showed growing results, and retrogradation enthalpy and the ageing rate reduced. SEM results found that with inulin addition, wheat starch presents flocculent and fold structure. The noodles with 5% inulin addition were frozen‐stored for 50 days after the cooking process. Inulin addition could retard the hardness and viscosity increase during the frozen storage. Besides, cooking loss rates and sensory property‐treated samples were better than the control.
Effect of simulated acidic and salty fermentation conditions on kinetic growth parameters and probiotic potential of Lactobacillus acidipiscis and Lactobacillus pentosus
Authors: Benavente Beltrán Francisco Javier , Morales Barrera Liliana , González‐González Cid Ramón , Andrade Velasquez Amaury , Melgar‐Lalanne Guiomar
Published: November 2020

The technological stress during food processing may alter the beneficial interactions of food‐associated Lactobacillus on the host. The effect of initial combined acidic (pH 5.0) and osmotic stress (NaCl 5 %, w/v with or without CaCl2 0.02 %, w/v) typically present in vegetable fermentations and cheesemaking were investigated. The growth kinetics prediction, hydrophobicity, auto‐aggregation, in vitro survival and adhesion were determined in Lactobacillus acidipiscis and Lactobacillus pentosus isolated from a Mexican salty cheese. The growth was modelled with the modified Gompertz equation (R > 0.99; RMSE < 0.01). The lag phase increased (>10 h), and auto‐aggregation was reduced. Hydrophobicity and S‐layer total proteins varied. Gut survival reduced >4 log 10 units compared to the initial intake. Nevertheless, adhesion remained the same. Hence, combined stress affected the technological and physiological properties of both strains negatively. Further research is needed to identify the effect of the combined stress on the potential bioactivity of the strains.
Identification of cassava quality attributes preferred by Ugandan users along the food chain
Authors: Iragaba Paula , Hamba Sophia , Nuwamanya Ephraim , Kanaabi Michael , Nanyonjo Ritah Ann , Mpamire Doreen , Muhumuza Nicholas , Khakasa Elizabeth , Tufan Hale Ann , Kawuki Robert Sezi
Published: November 2020

This study aimed to identify cassava quality attributes preferred by users along the food chain, in order to provide breeders with criteria for prioritisation. Survey and consumer‐testing studies were conducted within Apac and Luwero districts in Uganda. Additionally, sensory evaluation by trained panellists was conducted to determine descriptors for assessing quality of boiled roots. Results revealed softness of boiled roots and in‐ground storability as key attributes influencing varietal preference besides high yield, non‐bitter roots, disease resistance, early maturity and drought resistance. For some attributes like in‐ground storability, preference differed significantly between locations and showed differentiation by gender. Local varieties were found to be superior in quality attributes. From sensory evaluation, twenty‐one descriptors associated with appearance, texture, taste and aroma of boiled roots were determined. Findings from this study are vital for breeders to adopt gender‐responsive approaches in order to develop varieties that meet the needs and preferences of end users.
Accumulation of phenolics, antioxidant and antiproliferative activity of sweet corn (Zea mays L.) during kernel maturation
Authors: Hu Xiaodan , Liu Haiying , Yu Yongtao , Li Gaoke , Qi Xitao , Li Yuliang , Li Tong , Guo Xinbo , Liu Rui Hai
Published: November 2020

Phenolic profiles and gene expression pattern in their synthetic pathway, total antioxidant activities and antiproliferative activities in two genotypes of sweet corn (YT16 and YT28) during kernel maturation were analysed. Results showed that increasing trends of phenolics and flavonoids in the two genotypes of kernels from 10 to 30 days after pollination (DAP). Gallic acid, chlorogenic acid, p‐coumaric acid and ferulic acid were identified and quantified as the main phenolic compounds in both genotypes of kernels. High expressing levels of C4O and PAL resulted in the increasing phenolic contents. Higher expressing levels of CHS in YT28 led to higher flavonoid contents than that in YT16. The phenolic contents, antioxidant capacities and antiproliferative abilities of the two genotypes of sweet corn were competitive comparing to many fruits and vegetables. In addition, the maturation process of sweet corn could raise the kernel’s bioactive ability as well as nutritional values.
Limitations of a calibrated, quantitative APC‐R assay under routine conditions
Authors: Jilma‐Stohlawetz Petra , Lysy Katharina , Sunder‐Plassmann Raute , Belik Sabine , Jilma Bernd , Pabinger Ingrid , Quehenberger Peter
Published: November 2020

Introduction

The aim of this study was to evaluate the Hemoclot Quanti. V‐L assay in various clinical conditions.

Methods

We compared the Hemoclot Quanti.V‐L assay with DNA testing and with the Pefakit assay in 60 normal (no mutation) vs carriers of the factor V (FV) Leiden mutation (56 heterozygous and three homozygous). We further investigated the interference of lupus anticoagulant on test results in normal and heterozygous individuals and of direct oral anticoagulants (DOACs) at trough and peak levels. Additionally, DOAC‐Remove was tested in samples containing DOACs at peak levels. We further evaluated the influence of FV deficiency on this quantitative assay.

Results

There was a 100% agreement between the Quant. V‐L assay and DNA testing in 60 normal individuals. However, 1.85% of heterozygous and 33% of homozygous samples were falsely classified with the quantitative assay, and no misclassification was observed with the Pefakit assay. Lupus anticoagulant did not influence the test results of the quantitative assay. DOACs also interfered with test results in heterozygous patients, but this effect was prevented with the DOAC‐Remove procedure. Even mild FV deficiency affected the test results of the quantitative assay in heterozygous patients leading either to misclassification or the need for subsequent PCR testing.

Conclusion

The quantitative FV‐L assay has several limitations, especially FV deficiency and the presence of DOACs have to be ruled out before running this quantitative assay.
Impact of cancer therapy on post‐treatment ejaculation disorder and sexual life in testicular cancer survivors
Authors: Koyama Juntaro , Yamashita Shinichi , Yamada Shigeyuki , Fujii Shinji , Goto Takuro , Katayama Hiromichi , Satake Yohei , Sato Takuma , Shimada Shuichi , Kawasaki Yoshihide , Kawamorita Naoki , Mitsuzuka Koji , Arai Yoichi , Ito Akihiro
Published: November 2020

Objective

To evaluate the impact of cancer therapy on post‐treatment ejaculation in patients with testicular cancer.

Methods

A total of 74 testicular cancer survivors provided completed International Index of Erectile Function‐15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered “1 = almost never/never” or “2 = a few times” for questionnaire number 9 (ejaculation frequency) were defined as having “ejaculation disorder.”

Results

Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post‐treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function‐15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001).

Conclusion

Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life.
Regulation of circadian behavioural output via clock‐responsive miR‐276b
Authors: Zhang R. , Du J. , Zhao X. , Wei L. , Zhao Z.
Published: November 2020

Growing evidence indicates that microRNAs play numerous important roles. However, the roles of some microRNAs involved in regulation of circadian rhythm and sleep are still not well understood. In this study, we show that the miR‐276b is essential for maintaining both sleep and circadian rhythm by targeting tim, npfr1 and DopR1 genes, with miR‐276b deleted mutant flies sleeping more, and vice versa in miR‐276b overexpressing flies. Through analysing its promoter, we found that mir‐276b is responsive to CLOCK and regulates circadian rhythm through the negative feedback loop of the CLK/CYC‐TIM/PER. Furthermore, miR‐276b is broadly expressed in the clock neurons and the central complexes such as the mushroom body and the fan‐shape body of Drosophila brain, in which up‐regulation of miR‐276b in tim, npfr1 and DopR1 expressing tissues significantly causes sleep decreases. This study clarifies that the mir‐276b is very important for participating in regulation of circadian rhythm and sleep.
Viperin binds STING and enhances the type‐I interferon response following dsDNA detection
Authors: Crosse Keaton M , Monson Ebony A , Dumbrepatil Arti B , Smith Monique , Tseng Yeu‐Yang , Van der Hoek Kylie H , Revill Peter A , Saker Subir , Tscharke David C , G Marsh E Neil , Beard Michael R , Helbig Karla J
Published: November 2020

Viperin is an interferon‐inducible protein that is pivotal for eliciting an effective immune response against an array of diverse viral pathogens. Here we describe a mechanism of viperin’s broad antiviral activity by demonstrating the protein’s ability to synergistically enhance the innate immune dsDNA signaling pathway to limit viral infection. Viperin co‐localized with the key signaling molecules of the innate immune dsDNA sensing pathway, STING and TBK1; binding directly to STING and inducing enhanced K63‐linked polyubiquitination of TBK1. Subsequent analysis identified viperin’s necessity to bind the cytosolic iron‐sulfur assembly component 2A, to prolong its enhancement of the type‐I interferon response to aberrant dsDNA. Here we show that viperin facilitates the formation of a signaling enhanceosome, to coordinate efficient signal transduction following activation of the dsDNA signaling pathway, which results in an enhanced antiviral state. We also provide evidence for viperin’s radical SAM enzymatic activity to self‐limit its immunomodulatory functions. These data further define viperin’s role as a positive regulator of innate immune signaling, offering a mechanism of viperin’s broad antiviral capacity.
Development of low‐loss lead‐germanate glass for mid‐infrared fiber optics: II. preform extrusion and fiber fabrication
Authors: Wang Pengfei , Ng Alson Kwun Leung , Dowler Alastair , Ebendorff‐Heidepriem Heike
Published: November 2020

For lead‐germanate glass fibers, reducing the content of hydroxyl (OH) groups and the formation of metallic Pb species is essential to pave the way for their applications as low‐loss mid‐IR fiber optics since OH and metallic Pb species cause intense absorption and scattering loss, respectively, in the mid‐IR spectral range. The first part of this study reported the optimization of the glass melting procedure to obtain low amount of OH while preventing formation of metallic Pb species in lead‐germanate glass. Here, the second part of this study reports the investigation of the process conditions to fabricate low‐loss lead‐germanate glass fiber through further understanding of the co‐effects of glass melting and heat treatment atmospheres on the formation of nano‐ and micron‐scale metallic Pb species in both the as‐produced and heat treated lead‐germanate glasses. Finally, using this advance in knowledge, we successfully fabricated low‐loss lead‐germanate glass fibers with no presence of reduced metallic Pb particles by optimizing dehydration agent, glass melting, preform extrusion and fiber drawing conditions. The optimized fabrication conditions reduced the unstructured fiber loss by almost one order to <0.3 dB/m at 1.55 μm.
Re‐entrant ferroelectric relaxor phenomena in the (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3 system
Authors: Gupta Sanu K. , Gibbons Brady J. , Mardilovich Peter , Cann David P.
Published: November 2020

The solid solution (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3, (0.00 ≤ x ≤ 0.12) was investigated to examine the phase equilibria, dielectric and electromechanical properties. The composition corresponding to x = 0.00 exhibits tetragonal symmetry with the expected classical ferroelectric (FE) behavior. The system exhibited FE to relaxor crossover with the addition of lead zirconate at the composition x = 0.05. This is indicated by typical relaxor characteristics such as a transition to the global pseudocubic phase, a constriction in the FE hysteresis loop, and a sudden decrease in the negative strain accompanied by an increase in maximum strain. Most notably, with a further increase in x (>0.05), there is evidence for a return to a FE phase that exhibits classical FE characteristics. The combined results demonstrate that there exists a narrow FE‐relaxor boundary near x = 0.05, where FE and relaxor phases coexist. At the critical composition, enhancement in the piezoelectric properties, including an increase in the effective (350 pm/V) was observed. This transition in the electromechanical properties is consistent with changes observed in the phase equilibria for this solid solution. The crystal structure transitions from tetragonal symmetry for x = 0.00, to pseudocubic symmetry for the relaxor compositions (x = 0.05), and finally to a lower symmetry perovskite phase for the re‐entrant FE phase (x> 0.05). This composition‐induced transition from FE to relaxor to a re‐entrant FE state in the (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3 system is unusual among relaxor FE systems and thus is of great scientific and technological interest.
Peripheral memory T‐cell profile is modified in patients undergoing periodontal management
Authors: Medara Nidhi , Lenzo Jason C. , Walsh Katrina A. , Holden James A. , Reynolds Eric C. , Darby Ivan B. , O’Brien‐Simpson Neil M.
Published: November 2020

Aims

T‐cells are known to have a role in periodontitis, however, the effect of periodontal therapy on peripheral memory T‐cells is unclear. This study evaluated variation in peripheral memory T‐cells and red complex bacteria in sub‐gingival plaque in patients undergoing periodontal management.

Methods

Peripheral blood mononuclear cells and sub‐gingival plaque were collected from 54 periodontitis patients at baseline, 3‐, 6‐ and 12‐months post‐therapy and 40 healthy controls. Periodontitis patients were divided into treatment outcome (TxO) groups based on prevalence of sites with probing depth ≥5 mm as good (<10% of sites), moderate (10–20%) or poor (>20%) at study conclusion. Naïve (TN—CCR7+CD45RA+), central memory (TCM—CCR7+CD45RA−), effector memory (TEM—CCR7−CD45RA−) and effector memory T‐cells re‐expressing CD45RA (TEMRA—CCR7−CD45RA+) were phenotyped using flow cytometry in CD4+, CD8+, CD4+CD8+ and CD4−CD8− T‐cells and red complex bacteria were quantified using qPCR.

Results

At baseline, periodontitis subjects had significantly greater mean probing depths and Porphyromonas gingivalis proportions, lower TN but higher CD4+ TCM, CD8+ TCM, CD4+CD8+ TEM and CD4−CD8− TEM cell proportions compared to health. Periodontal therapy decreased mean probing depths, P. gingivalis proportions, TEM and CD4+ and CD8+ TCM cells, but increased TN and CD4+ and CD8+ TEMRA cells. The T‐cell profile in the good TxO group showed therapy‐related changes in CD4+ TEM, and CD8+ TN and TEM cells, whereas, no changes were observed in the poor TxO group.

Conclusion

Management and the reduction in red complex bacteria were associated with changes in peripheral memory T‐cells in periodontitis.
Favorable effect of sodium–glucose cotransporter 2 inhibitor, dapagliflozin, on non‐alcoholic fatty liver disease compared with pioglitazone
Authors: Cho Kyu Yong , Nakamura Akinobu , Omori Kazuno , Takase Takahiro , Miya Aika , Yamamoto Kohei , Nomoto Hiroshi , Kameda Hiraku , Taneda Shinji , Kurihara Yoshio , Aoki Shin , Atsumi Tatsuya , Miyoshi Hideaki
Published: November 2020

Aims/Introduction

Sodium–glucose cotransporter 2 inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has shown non‐inferiority compared with pioglitazone for glycemic control, and superiority regarding weight reduction in patients with type 2 diabetes. We carried out a secondary analysis for the favorable effects of sodium–glucose cotransporter inhibitors for NAFLD.

Materials and Methods

In this multicenter, open‐label, prospective, randomized, parallel‐group comparison trial, patients taking pioglitazone for ≥12 weeks were randomly switched to dapagliflozin or continued pioglitazone for a further 24 weeks. The fatty liver index (FLI), consisting of body mass index, triglycerides, waist circumference and γ‐glutamyl transpeptidase, was used for the evaluation of NAFLD.

Results

A total of 53 participants with NAFLD (27 dapagliflozin; 26 pioglitazone) were included in this analysis. FLI decreased significantly in the dapagliflozin group (48.7 ± 23.4 to 42.1 ± 23.9) compared with the pioglitazone group (49.0 ± 26.1 to 51.1 ± 25.8; P < 0.01). Multiple linear regression analysis showed that the changes in FLI had a significantly positive correlation with changes in glycated hemoglobin (P = 0.03) and insulin level (P < 0.01) in the dapagliflozin group.

Conclusion

Dapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.
Macrophage‐activating lipopeptide‐2 and corticotropin‐releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl‐CoA desaturase and fatty acid desaturase 2
Authors: Zouboulis C.C. , Angres S.
Published: November 2020

Background

The macrophage‐activating lipopeptide‐2 (MALP‐2) activates cells carrying a functional Toll‐like receptor (TLR)‐2/6. Human sebocytes express functional TLR‐2, TLR‐4 and CD14. Upregulation of stearoyl‐CoA desaturase (SCD) and fatty acid desaturase‐2 (FADS2) expression induces pro‐inflammatory sebaceous activity. On the other hand, corticotropin‐releasing hormone (CRH) is likely to serve as an autocrine stress hormone in human sebocytes. In addition to its antiproliferative, lipogenetic and androgen‐activating functions, CRH exhibits a pro‐inflammatory action and its expression is upregulated in acne‐involved sebaceous glands.

Objective

Determination of the pro‐inflammatory function of MALP‐2 and CRH and clarification of the option that MALP‐2 and/or CRH activity on human sebocytes might be mediated through SCD and/or FADS2.

Methods

SZ95 sebocytes were treated with MALP‐2, CRH and the SCD inhibitor/ligand FPCA. SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion were investigated. Intracellular CRH levels were assessed under treatment with CRH, MALP‐2, linoleic acid and arachidonic acid. Phorbol 12‐myristate 13‐acetate and dexamethasone served as positive and negative controls, respectively.

Results

MALP‐2 upregulated SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion from SZ95 sebocytes. Co‐incubation of SZ95 sebocytes with MALP‐2/FPCA did not affect the MALP‐2‐induced SCD mRNA upregulation but reduced FADS2 mRNA levels and inhibited IL‐8 secretion. CRH induced an early, low‐level SCD and FADS2 upregulation and TLR‐2 and IL‐8 secretion. High intracellular CRH concentrations could be detected early after CRH treatment and persisted up to 24 h. MALP‐2 stimulated intracellular CRH levels.

Conclusions

MALP‐2 stimulates the inflammatory signalling in human sebocytes through SCD and FADS2 activation. Inhibition of FADS2 mRNA levels and IL‐8 secretion through MALP‐2/FCPA co‐incubation and diminution of fatty acid unsaturation might lead to a reduction of pro‐inflammatory sebaceous lipids. CRH upregulates inflammatory signalling via the SCD/FADS2 pathway, and MALP‐2 selectively enhances CRH levels in human sebocytes.
Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non‐target sites, for DAA‐based treatment and retreatment outcome
Authors: Fahnøe Ulrik , Pedersen Martin S. , Sølund Christina , Ernst Anja , Krarup Henrik B. , Røge Birgit T. , Christensen Peer B. , Laursen Alex L. , Gerstoft Jan , Thielsen Peter , Madsen Lone G. , Pedersen Anders G. , Schønning Kristian , Weis Nina , Bukh Jens
Published: November 2020

Direct‐acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance‐associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment‐failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral‐titre data were compared between the two patient groups, and HCV full‐length open reading frame deep‐sequencing was performed. The proportion of HCV NS5A‐RASs at baseline was higher in treatment‐failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment‐failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B‐substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3‐helicase and NS5A‐domain‐III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
Functional diversity of attachment and grooming leg structures is retained in all but the smallest insects
Authors: Boudinot B. E. , Beutel R. G. , Gorb S. N. , Polilov A. A.
Published: November 2020

Miniaturization strongly affects functional morphology. Whereas some anatomical structures are barely affected by scaling, others can fundamentally change as the body becomes ever smaller. No prior study has focused on the effect of miniaturization on grooming and attachment structures in Hymenoptera, which can be highly diverse and complex. Through comparative description of the legs of the extremely small wasps of the families Mymaridae and Trichogrammatidae, we evaluate the functional and phylogenetic patterns concerning possible functional effects of miniaturization. On the one hand, the studied species retain some features characteristic of other Chalcidoidea, while on the other, they display some parallelisms associated with miniaturization in leg structure. These observations support a two‐stage morphocline of miniaturization, wherein the first stage is characterized by the preservation of structural complexity and retention of all basic functions, as for instance in examined Megaphragma and the females of Dicopomorpha. The second stage is characterized by a significant simplification, with the loss of redundant non‐essential functions, as observed for the males of Dicopomorpha, which have grossly reduced leg structures, including total loss cleaning devices. Whether these stages are ordered or unordered should be evaluated in future study. Functional optimization of attachment in male Dicopomorpha is indicated by the highly derived mushroom‐shaped tarsi, complemented by novel grappling spurs on the hindfeet, possibly for copulation. Our observations underline adaptive trade‐offs in the expression of complex and multifunctional leg structures at extreme scales.